Next Article in Journal
Filovirus Entry: A Novelty in the Viral Fusion World
Next Article in Special Issue
Feline Immunodeficiency Virus in South America
Previous Article in Journal
Back to BAC: The Use of Infectious Clone Technologies for Viral Mutagenesis
Previous Article in Special Issue
Construction and Testing of orfA +/- FIV Reporter Viruses

Viruses 2012, 4(2), 236-257; doi:10.3390/v4020236

Review
Emerging Viruses in the Felidae: Shifting Paradigms
Stephen J. O’Brien 1,*,, Jennifer L. Troyer 2, Meredith A. Brown 3, Warren E. Johnson 1, Agostinho Antunes 4, Melody E. Roelke 2 and Jill Pecon-Slattery 1
1
Laboratory of Genomic Diversity, National Cancer Institute-Frederick, Frederick, MD 21702, USA; Email: warjohns@mail.nih.gov (W.E.J.); slatterj@mail.nih.gov (J.P.-S.)
2
SAIC-Frederick, Inc., National Cancer Institute-Frederick, Frederick, MD 21702, USA; Email: troyerj@mail.nih.gov (J.L.T.); Melody.Roelke-Parker@nih.gov (M.E.R.)
3
Banfield Pet Hospital, 800 NE Tillamook Street, Portland, OR 97213, USA; Email: Meredith.Brown@banfield.net
4
CIMAR, University of Porto, Rua dos Bragas, 177, Porto 4050-123, Portugal; Email: aantunes@ciimar.up.pt
Present Address: Theodosius Dobzhansky Center for Genome Bioinformatics, St. Petersburg University, St. Petersburg, 190000, Russia.
*
Author to whom correspondence should be addressed; Email: lgdchief@gmail.com; Tel.: +1-240-446-1021; Fax: +1-301-662-1413.
Received: 1 December 2011; in revised form: 21 December 2011 / Accepted: 11 January 2012 /
Published: 7 February 2012

Abstract

: The domestic cat is afflicted with multiple viruses that serve as powerful models for human disease including cancers, SARS and HIV/AIDS. Cat viruses that cause these diseases have been studied for decades revealing detailed insight concerning transmission, virulence, origins and pathogenesis. Here we review recent genetic advances that have questioned traditional wisdom regarding the origins of virulent Feline infectious peritonitis (FIP) diseases, the pathogenic potential of Feline Immunodeficiency Virus (FIV) in wild non-domestic Felidae species, and the restriction of Feline Leukemia Virus (FeLV) mediated immune impairment to domestic cats rather than other Felidae species. The most recent interpretations indicate important new evolutionary conclusions implicating these deadly infectious agents in domestic and non-domestic felids.
Keywords:
FIV; FCoV; FeLV; Felidae

1. Introduction

The aloof and elusive nature of domestic cats, Felis catus, the world’s most popular pet, is endearing to some and exasperating to others. Including feral cats, there are 600 million to one billion domestic cats worldwide, an astounding number for an animal that contributes little to nothing in the way of work, milk or meat to the human endeavor. The domestic cat is the consequence of a remarkable domestication experiment that commenced in near east Asia some 10,000 years ago, when the shy and reclusive desert wildcat (Felis sylvestris) gradually morphed into the venerated, audacious, and familiar human pet. Domestication processes began when Neolithic hunter-gatherers settled in agricultural villages in a rich area of the Middle East we call the Fertile Crescent. These first farmers cultivated wild precursors of corn, wheat and barley, while others herded and penned cattle, sheep, goats and even pigs. The domestication strategy fed and clothed many more people than hunters could support. Contemporaneously, the wildcats fed on scraps, befriended the settlers and began a legacy of human companionship that is unprecedented in human civilization [1].

At first glance, the major benefit of cat domestication appears to be human companionship, but this role is rapidly expanding to encompass issues in human health. Viral infectious diseases in cats have patterns of evolution, virulence and pathogenicity that offer strong parallels to related viruses in humans (Table 1). Feline coronavirus (FCoV), common in domestic cats, is a close relative of the human SARS coronavirus that afflicted the world in 2003, when a reported 8096 infections in 23 countries killed 774 people before the outbreak subsided [2]. In the 1960’s, the discovery of feline leukemia virus and its ability to recombine with host cellular oncogenes resulted in a better understanding of numerous feline and human malignancies [3]. Feline Immunodeficiency Virus (FIV), first identified in 1986 as the causative agent of an AIDS-like syndrome in a California cat colony [4], remains a compelling natural model of immunodeficiency pathogenesis, mirroring the HIV-AIDS epidemic that has dominated the past human generation. Add to that feline calicivirus, feline herpes virus, feline foamy virus and panleukopenia parvovirus; cat species provide a panoply of infectious disease models for many devastating human diseases (Table 1).

Table Table 1. Examples of domestic cat viruses with human homologues *.

Click here to display table

Table 1. Examples of domestic cat viruses with human homologues *.
Feline VirusHuman Homologue
Feline Leukemia Virus (FeLV) [5]Human T-Cell Leukemia Virus (HTLV) [6]
Feline Immunodeficiency Virus (FIV) [7]Human Immunodeficiency Virus (HIV-AIDS) [8]
Feline Coronavirus (FCoV) [9]SARS-Coronavirus (Severe acute respiratory syndrome) [10]
Feline Sarcoma Virus (FSV) [11]~20 Human Oncogenes [12]
Avian H5N1 Influenza [13]Avian H5N1 Influenza [14]
Feline Herpes Virus (FHV) [15]Cytomegalovirus (CMV-retinitis)
Feline Foamy Virus (FFV) [16]Human Foamy Virus (No pathology) [17]
Feline Calicivirus (FCV) [18]Human Calicivirus (Diarrhea, vomiting) [19]
Feline Parvovirus (FPV) [20]Human B19 Parvovirus (Fifth disease) [21]
Feline Morbillivirus (CDV) [22]Human Morbillivirus (Measles) [23]

* Many references exist for each virus in both cat and human, here we provide single references as examples.

In this review, we will attempt to highlight how recent advances in our understanding of three cat viruses (FCoV, FIV, and FeLV) have revised conventional wisdoms. We illustrate how previous tenets, based on limited available evidence, were revised and amended due to new insights from genetic studies of cat populations.

2. Feline Coronavirus (FCoV) Pathogenesis in Domestic Cats

Feline infectious peritonitis (FIP) is a fatal, progressive, and immune-augmented disease of cats caused by infection with feline coronavirus (FCoV). Coronaviruses are enveloped positive-stranded RNA viruses that infect a wide range of vertebrate species [24]. The clinical manifestation of FCoV infection can present either as the pathogenic disease manifestation or feline infectious peritonitis virus (FIPV) or the more common, benign or mild enteric infection (feline enteric coronavirus—FECV—asymptomatic) [25,26]. Although FCoV is common in domestic, feral and non-domestic cat populations world-wide (seroprevalence from 20–100%), less than 10% of FCoV seropositive cats develop FIP [27,28,29]. Cats infected with FCoV that show no evidence of disease are thought to represent chronic carriers of FCoV and may pose an FIP risk to other cats [27,30,31].

FIP pathology is characterized typically by severe systemic inflammatory damage of serosal membranes and widespread pyogranulomatous lesions, occurring in lung, liver, lymph tissue, and brain [32]. Evidence suggests that the host immune system is crucial in this pathogenesis; both profound T-cell depletion from the periphery and lymphatic tissues and changes in cytokine expression are observed in end stage FIP [33,34].

Viral gene determinants likely play an important role in FCoV pathogenicity and virulence. Coronaviruses are a large family of enveloped, single stranded, positive sense, non-segmented RNA viruses. Characterized by a genome size roughly 30 kb in length, coronaviruses are the largest RNA virus so far described [35]. However, there is no effective treatment, vaccine, nor a diagnostic protocol that can discriminate the avirulent FECV from the pathogenic FIP strains.

Conventional wisdom accepts the “in vivo mutation transition hypothesis” also called the “internal mutation hypothesis” which postulates that viral mutations occur in healthy FCoV infected cats giving rise to virulent virions that spread systemically and lead to FIP pathogenesis [36,37]. Although this hypothesis has been widely cited [9,25,27,30,31,36,37,38,39] the precise nature of the mutation responsible for pathogenesis has never been identified. Various studies have speculated that variants in the spike protein, membrane protein, or NSP 3c [40] allow infection of macrophages, systemic dissemination, and fatal disease manifestation [36,37].

An alternative “circulating avirulent and virulent FCoV hypothesis” suggests that distinctive benign and pathogenic strains of FCoV circulate in a population, and those individuals exposed to the virulent strains, with the appropriate predisposition, develop disease sequelae. Virological precedence for this possibility has been reported for dengue fever virus and equine Venezuelan encephalitis virus, both of which demonstrate circulating virulent and avirulent forms [41,42].

To test between these alternatives, Brown et al. compared the FCoV gene sequence patterns among FIP afflicted cats and FCoV infected asymptomatic cats collected from households in Maryland between 2004 and 2006 [43]. Brown et al. [43] reasoned that a phylogenetic analysis of virogene sequences would be informative in discriminating between the two hypotheses as follows: if the “circulating virulent-avirulent FCoV hypothesis” were the case, then a “monophyletic” pattern of FCoV variation would cluster pathogenic cats separately from healthy cats, since a circulating pathogenic virus would have accumulated mutations over time to drift apart from the avirulent FCoV strain. Alternatively if the “in vivo mutation hypothesis” were the case, then FCoV from healthy and sick cats would cluster together (paraphyletic inter-mixing) in accordance with geographic locale (i.e., phylogeographic clustering), and not pathogenic virulence.

Brown et al. [43] inspected the phylogenetic clustering of four FCoV genes (pol replicase; spike, membrane and NSP 7b; Figure 1) in 56 cats (8 FIP and 46 healthy) from Maryland catteries. The results, illustrated by the phylogenetic analysis in Figure 1, were definitive in clustering the virus from sick FIPV cats together in a monophyletic group, quite distinctive from the FCoV derived from the healthy cats. In one cat (FCA-4590) that progressed from a healthy FECV positive state to FIP disease over the course of two years, the recovered virus from the earlier time point clustered with other FCoV -innocuous strains while the virus isolated when the cat showed disease symptoms clearly grouped with genetically distinct virulent FIP strains, as if the innocuous FCoV were replaced by a second virulent FIPV strain (Figure 1).

Brown et al. [43] interpreted these results as supporting the concept that there were at least two distinctive circulating forms of FCoV in Maryland, one which caused FIP, and a second that did not. Further, they identified certain amino acid signatures of the membrane gene that were diagnostic of FIPV versus avirulent circulating FCoV in the feral cat population. Although these results would tend to support the circulating variant explanation, they need to be replicated and extended to other geographic locales to accurately reflect variation possible in the world’s 700 million cats. One recent study documented paraphyly (mixing) of FIP and healthy FCoV infected cat strains in Europe, which would seem to complicate the interpretation [44]. Thus, current evidence would suggest that FIP etiology is more complex than either hypothesis alone would suggest. Perhaps the causative mutation has not been found because multiple mutations may result in increased pathogenicity. It is also possible that some strains are more prone to these mutations than others; a situation that would mimic the circulating avirulent and virulent hypothesis, as well as explain the results seen in Brown et al. Future studies exploring both viral and host genetic determinants of disease in FIP [45,46], should reveal opportunities for the management of this disease including the possible development of ante mortem screening tools for genetic disposition for disease as well as the discrimination of virulent versus avirulent strains of FCoV.

3. Feline Immunodeficiency Virus: FIV Pathogenesis in Felidae Species

Feline Immunodeficiency Virus (FIV) was first discovered 25 years ago [4,47] as a cat lentivirus with structural, genomic, and pathogenic parallels to HIV [48,49,50]. Infected domestic cats develop symptoms of immune depletion including a precipitous drop in CD4 bearing T-lymphocytes, neutropenia, lymphadenopathy and susceptibility to normally harmless bacteria, fungal lesions, wasting, and rare cancers. FIV is endemic in feral cat populations and has diverged into several phylogenetic clade types across the world [51,52,53,54,55].

Viruses 04 00236 g001 1024
Figure 1. Phylogenetic tree of cloned feline infectious peritonitis (FIP) membrane sequences (655 bp) from 19 healthy (feline enteric coronavirus (FECV); green) and 8 symptomatic (feline infectious peritonitis virus FIPV; red) cats [43]. One cat, Fca-4590, was sampled when healthy and then at death caused by FIP. Shown is the maximum likelihood tree constructed from 655 bp of the membrane gene. The number of FECV and FIP cases followed by the number of cloned sequences is indicated in parenthesis. The labels for each sequence include location W, Weller Farm; F, Frederick Animal Shelter; S, Seymour Farm; M, Mount Airy Shelter; A, Ambrose Farm), 4-digit cat identification number, tissue source (fe, feces; af, ascites fluid; co, colon; li, liver; sp, spleen; in, intestine; je, jejunum; ln, lymph node), 2-digit year (e.g., 04 = 2004), and number of clones for each sequence. Bootstrap values are shown (MP/minimum evolution/ML) above branches. Where ML tree was congruent with MP tree, branch lengths are indicated below branches; the number of homoplasies is in parenthesis after the branch length. Virus sequence obtained from cat no. 4590 in May 2004 and at the time of death due to FIP in December 2004. The transitional individual serial samples are indicated with open circles (first sample) and solid circles (second sample). Scale bar indicates substitutions/site.

Click here to enlarge figure

Figure 1. Phylogenetic tree of cloned feline infectious peritonitis (FIP) membrane sequences (655 bp) from 19 healthy (feline enteric coronavirus (FECV); green) and 8 symptomatic (feline infectious peritonitis virus FIPV; red) cats [43]. One cat, Fca-4590, was sampled when healthy and then at death caused by FIP. Shown is the maximum likelihood tree constructed from 655 bp of the membrane gene. The number of FECV and FIP cases followed by the number of cloned sequences is indicated in parenthesis. The labels for each sequence include location W, Weller Farm; F, Frederick Animal Shelter; S, Seymour Farm; M, Mount Airy Shelter; A, Ambrose Farm), 4-digit cat identification number, tissue source (fe, feces; af, ascites fluid; co, colon; li, liver; sp, spleen; in, intestine; je, jejunum; ln, lymph node), 2-digit year (e.g., 04 = 2004), and number of clones for each sequence. Bootstrap values are shown (MP/minimum evolution/ML) above branches. Where ML tree was congruent with MP tree, branch lengths are indicated below branches; the number of homoplasies is in parenthesis after the branch length. Virus sequence obtained from cat no. 4590 in May 2004 and at the time of death due to FIP in December 2004. The transitional individual serial samples are indicated with open circles (first sample) and solid circles (second sample). Scale bar indicates substitutions/site.
Viruses 04 00236 g001 1024

FIV has infected many of the 37 described species of the Felidae family [56] (Table 2). It is speculated that most cat species (Table 2) acquired the virus within the last 10–20,000 years, but patterns of evolution within both virus and host genomes, suggest FIV may have existed far longer in some species such as lion [57,58]. Phylogenetic analysis of individual FIV-isolates in a dozen or more species of felids [7,58,59,60,61] demonstrates reciprocal monophyly of FIV among various species (that is, every lion strain has as its closest relative another lion isolate rather than FIV from a different cat species) (Figure 2). These phylogenetic results supported the notion that although FIV occasionally can move from species to species [62,63,64], these events are exceedingly rare, leading to a monophyletic expansion of viral genome sequence diversity within every species, so that most cat species carry their own distinct version of FIV [65,66,67,68].

Table Table 2. Summary of FIV prevalence tested by western blot (AB) and PCR in Felidae.

Click here to display table

Table 2. Summary of FIV prevalence tested by western blot (AB) and PCR in Felidae.
SpeciesCommon NameFree RangingCaptiveCitation
AB+PCR+AB+PCR+
Felis silvestrisEuropean wild cat5/1250/34/13 [7,69,70,71,72]
F. libycaAfrican wild cat 1/160/1[7]
F. bietiChinese desert cat
F. margaritaDesert cat0/14 6/130/7[7,69]
F. nigripesBlack-footed cat 3/110/4[7]
F. chausJungle cat 5/170/6[7]
Otocolobus manulPallas cat10/277/2612/192/2[7,43]
Prionailurus rubiginosisRusty spotted cat 0/1 [7]
P. bengalensisAsian leopard cat1/121/10/81 [7,73,74]
P. viverrinusFishing cat 1/250/2[7]
P. planicepsFlat-headed cat0/2 1/9 [7]
Puma concolorPuma150/36061/12345/166 [7,61,75,76,77]
P. yagouaroundiJaguarundi 9/401/8[7,78]
Acinonyx jubatusCheetah22/3037/106/242 [7,75,79,80]
Lynx pardinusIberian lynx7/740/75 [7,81]
L. lynxEurasian lynx 0/10 [7,75]
L. canadensisCanada lynx0/92 1/20/1[7,82]
L. rufusBobcat32/11517/321/80/1[7,83]
Leopardus pardalisOcelot8/261/1410/880/6[7,75,78]
L. wiediiMargay1/51/14/881/3[7,78]
L. jacobitaAndean mountain cat
L. colocoloPampas cat 1/12 [7]
L. geoffroyiGeoffroy's cat1/60/18/450/7[7]
L. guignaKodkod 0/2 [7]
L. tigrinusTigrina 3/400/2[7,78]
Caracal caracalCaracal0/3 0/22 [7,79]
C. aurataAfrican golden cat 0/2 [7]
C. servalServal 0/4 [7,75]
Pardofelis badiaBay cat 0/1 [7]
P. temminckiiAsian golden cat0/1 3/290/2[7]
P. marmorataMarbled cat 2/100/3[7]
Panthera leoLion 212/32172/1321/1[7,75,80,84,85,86]
P. oncaJaguar 0/28/420/7[7,75,78]
P. pardusLeopard 7/101/960/1[7,75,79,80]
P. tigrisTiger0/1 25/2171/12[7,75]
P. uncaSnow leopard 3/771/2[7,75]
Neofelis nebulosaClouded leopard 4/590/2[7]

Bold numbers = congruence between AB and PCR; shaded = free-ranging “+”; bold letters = PCR free-ranging “+” animals.

Viruses 04 00236 g002 1024
Figure 2. Maximum likelihood phylogenetic tree of 72 non-identical FIV from seven carnivore species based on a region of pol-RT (420 bp) [7,58,65]. Circles indicate subtypes within FIVPle, FIVPco and FIVFca lineages.

Click here to enlarge figure

Figure 2. Maximum likelihood phylogenetic tree of 72 non-identical FIV from seven carnivore species based on a region of pol-RT (420 bp) [7,58,65]. Circles indicate subtypes within FIVPle, FIVPco and FIVFca lineages.
Viruses 04 00236 g002 1024

Originally, the absence of clear clinical pathology among FIV infected felids in zoological collections, and field observations of seemingly healthy (or asymptomatic) FIV in natural populations of felids fostered the view that FIV is pathogenic in domestic cats but not in other free ranging species of Felidae [60,87]. However, that conclusion now seems premature and over-simplified. For example, Roelke et al. [88]. mounted a detailed physical examination and associated clinical measures among 64 free ranging lions in Botswana and Tanzania between 1999 and 2006. They examined a suite of biochemical, clinical, and pathogenic manifestations of immune suppression and disease analogous to pathogenesis observed in FIV infected domestic cats, in HIV-infected AIDS patients and in simian immunodeficiency virus (SIV)-infected macaques (see citations [88]).

Multiple indications and sequelae of AIDS defining conditions were manifest amongst FIV infected lions compared to FIV negative lions; the statistical associations are summarized in Table 3. First, a marked depletion of CD4 bearing T lymphocytes was apparent in FIV infected lions, a prelude to immune collapse in well defined AIDS [88,89]. In addition there were multiple elevations in opportunistic infections (papilloma, gingivitis, dehydration during wet conditions, anemia, hyperalbuminemia, weight loss in the face of abundant prey, abnormal red cell parameters, depressed serum albumin, liver pathogenesis, and elevated gamma globulin). Further, spleen and lymph node biopsies from nine free ranging lions revealed evidence of lymphoid depletion, the hallmark of AIDS disease in human, cats and macaques. These findings strongly suggest FIV is contributing to the loss of immune competence in these lions. A similar pathogenic study of wild SIV-infected chimpanzees also revealed definitive evidence of pathology in that species after a decade of pronouncing chimps as resistant to SIV [90].

As most people infected with HIV do not actually die of HIV infection per se, rather from subsequent opportunistic infections (e.g., pneumocystis, CMV, Kaposi’s sarcoma, candidiasis and other infections) it seemed fair to ask whether FIV in large cats might contribute to secondary infection pathogenesis. An opportunity to inspect this occurred during the mid-1990s in Tanzania when an outbreak of canine distemper virus (CDV; a morbillivirus) eliminated ~1000 lions from the large Serengeti populations in a 10 month interval [91]. Because FIV prevalence in East African and Botswana lions approaches 100% in adults, the potential influence of FIV on CDV pathology was to us an interesting question.

Lions harbor six genetically distinct strains, or subtypes, of lion FIV (FIVPle) resolved by phylogenetic analyses [57,58] (Figure 2). These strains have distinct phylogeographic distributions, suggesting prolonged host association, perhaps predating the Late-Pleistocene expansions of lions roughly 325,000 years ago [57]. Two lion FIVPle strains, FIVPle E and FIVPle A, circulate in Botswana; while three very divergent strains FIVPle A, B, and C occur in the Serengeti [92,93]. Perhaps consequent of the highly social nature of lions, FIVPle infected lion populations have high prevalence of seropositive individuals, approaching 100% in adult animals [7,57,92] (Figure 3a).

Troyer et al. [94] recently examined the association of FIV strains with relative survival (from death) in the Serengeti lions during the CDV outbreak. A rather striking difference was seen in that FIVPle B infected lions were twice as likely to survive CDV compared to lions infected with alternative strains FIVPle A and FIVPle C (Figure 3b). The apparent FIVPle B associated protective influence was evident whether individuals were infected with a single strain or with multiple strains (Figure 3b). These observations would suggest that infection with FIVPle A or C might have increased the risk of mortality upon secondary CDV infection. This inference that certain FIVPle strains predispose carriers to CDV pathogenesis has some parallels with FIV strain-specific pathogenicity in domestic cats [95,96,97]. Further, the higher CDV mortality among of FIVPle A and C carrying individuals actually altered FIV strain incidence causing a rise in FIVPle B and a drop in FIVPle C during the course of the CDV outbreak (Figure 3c).

Table Table 3. Medical conditions present in HIV, SIV and FIV infections found in FIVPle infected wild lions compared with FIVPle negative lions. (Adapted from [48]).

Click here to display table

Table 3. Medical conditions present in HIV, SIV and FIV infections found in FIVPle infected wild lions compared with FIVPle negative lions. (Adapted from [48]).
Medical ConditionFIVPle NegativeFIVPle PositiveOdds RatioP Value
% Affected# Individuals% Affected# Individuals
Immunodeficiency
CD4 depletion Absolute number of CD4+ T-cells /mL in peripheral whole blood ±s.e.051008NA0.00015
Oral manifestations
Gingivitis401588.44311.40.00016
Papillomavirus14.31453.19476.820.01009
Chronic Inflammatory Response
Lymphadenopathy41.671276.6474.580.01900
Hyperglobulinemia01485.7146NA<2 × 10−9
Erythrocyte sedimentation rate13.331564.8637120.00076
(> 2 s.d. above mean)
Dehydration (> 4%)26.671563.04464.690.01408
Loss of Condition and Under Nutrition
Hair and coat abnormalities13.31552.27447.120.00840
Hypoalbuminemia (marker of cachexia) (serum albumin > 2 s.d. below mean) 01446.9446NA0.00129
Anemia (hemoglobin / PCV >2 s.d. below mean)11.111855.775210.090.00101
Cachexia/unexplained weight lossNot documentedObserved in 3 FIV+ populationsNANA
Lymphoid response evidence
Histopathologic evidence: Lymphoid activationNot documentedYes NANA
Histopathologic evidence: Lymphoid atrophy & depletionNot documentedYes NANA
Viruses 04 00236 g003 1024
Figure 3. Distribution, incidence and co-infection of canine distemper virus (CDV) and FIV in Serengeti lions. (a) Map of approximate pride home ranges during the CDV outbreak in April of 1994. Distribution of FIVPle subtypes by pride is shown here [87,93]. (b) Comparison of survival between lions with (dark grey) and without (light grey) FIVPle-B. Shown here are Chi‑squared p-values. Fisher’s exact two-tailed statistics are significant all subtype configurations (p = 0.028) and approaching significant for single subtype infection (p = 0.072). (c) FIVPle subtype distribution over time. Lions that were alive at the beginning of the CDV outbreak (N = 91) were sampled either prior to April 1994, during the month of April 1994, or after April 1994. Most of the 1994 sampling occurred in April after the peak mortality (approximate time shown here as a grey bar). Knowledge of subtype frequencies prior to April 1994 is primarily from samples collected from those animals in previous years. These regressions are significantly different (p = 0.001).

Click here to enlarge figure

Figure 3. Distribution, incidence and co-infection of canine distemper virus (CDV) and FIV in Serengeti lions. (a) Map of approximate pride home ranges during the CDV outbreak in April of 1994. Distribution of FIVPle subtypes by pride is shown here [87,93]. (b) Comparison of survival between lions with (dark grey) and without (light grey) FIVPle-B. Shown here are Chi‑squared p-values. Fisher’s exact two-tailed statistics are significant all subtype configurations (p = 0.028) and approaching significant for single subtype infection (p = 0.072). (c) FIVPle subtype distribution over time. Lions that were alive at the beginning of the CDV outbreak (N = 91) were sampled either prior to April 1994, during the month of April 1994, or after April 1994. Most of the 1994 sampling occurred in April after the peak mortality (approximate time shown here as a grey bar). Knowledge of subtype frequencies prior to April 1994 is primarily from samples collected from those animals in previous years. These regressions are significantly different (p = 0.001).
Viruses 04 00236 g003 1024

The statistical rigor associated with these conclusions is rather weak since the number of lions was limited (total = 119 lions) and should be interpreted cautiously. Nonetheless, the striking influence of FIV on lion immune function (Table 3), clinical disposition, and a potential ancillary role in CDV mortality (Figure 3b,c) affirms that FIV is likely pathogenic in lions. However, the degree to which viral pathogenicity is influenced by host genomics underlying the immune response, the role of secondary infections, stochastic events due to ecological and environmental factors, has yet to be described. Nonetheless, FIV is a potentially harmful agent in free ranging lions, as for housecats, and deserves further scrutiny in the other free ranging species afflicted with FIV [88,94].

4. FeLV Outbreak in Free Ranging Florida Pumas

Feline leukemia virus, a retrovirus of domestic cats, displays a prevalence of 1–8% among feral cats worldwide. Transmission is usually by direct contact, and outcome after exposure depends on several host and viral factors. In approximately one third of exposed cats, viremia is persistent and eventually results in clinical syndromes including some combination of immunosuppression, anemia and/or neoplasia [5,98]. Mortality among persistently infected domestic cats is high as 83% die within 3.5 years [99].

Like other Type C retroviruses, FeLV induces immune suppression making the cats susceptible to opportunistic infections and cancers. There are four naturally occurring exogenous FeLV strains FeLV-A, -B, -C, and -T, that are distinguished genetically by sequence differences in the env gene and by receptor interactions required for cell entry [100]. FeLV-A is the predominant subgroup circulating in feral cats and is often only weakly pathogenic [101]. The endogenous feline leukemia provirus sequences are transmitted vertically though the germ line as integrated provirus nested on several cat chromosomes. Among infected cats the pathogenic subgroups, FeLV-B, -C, and -T, are generated de novo by mutation or recombination in the env region between exogenous subgroup A virus and endogenous proviral sequences [5,102,103,104].

FeLV infection among non-domestic cats of the Felidae family is rare. Most reported infections involved captive animals that acquired FeLV by physical contact with FeLV-infected domestic cats, and in nearly all cases that were followed, the virus was cleared by the infected individuals [105,106]. Therefore, it was postulated that FeLV pathogenicity did not occur in exotic felids, simply because there were no endogenous FeLV present in species outside the domestic cat lineage. The outcome with a Florida panther FeLV outbreak in 2001–2006 was unexpected and served to change this hypothesis [105,107].

The Florida panther (Puma concolor coryi) is an endangered subspecies whose range was contiguous with other puma populations [108]. By the late 20th century, however, depredation, exploitation, human population growth and habitat destruction had reduced the population to an isolated relict population of fewer than 30 individuals [109]. In 1995, a Florida panther restoration management action relocated eight Texas cougars (Puma concolor stanleyii) to the Florida habitat in a hopeful rescue of the threatened subspecies. The population rebounded to over 100 individuals, doubling panther numbers, density, survival parameters and fitness [110,111,112].

Florida panthers have undergone continued surveillance from 1978 -2001 and routinely tested for several pathogens, including FeLV [105]. However, for the first time in early 2001, 23 panthers were discovered to carry antibodies for FeLV by ELISA that was confirmed by Western Blot. Clinical symptoms including lymphadenopathy, anemia, septicemia and weight loss rapidly appeared. Five panthers shown to carry FeLV antigens in their sera subsequently died of diseases compatible with FeLV etiology [105,107].

The rapid appearance and spread of FeLV in this Florida panther population was unprecedented among large cats and caused concern in the Felidae conservation community. FeLV was not thought to cause serious disease in species other than in cats closely related to domestic cats (F. catus, F. sylvestris, F. margarita, F. nigripes and F. bieti) because only these Felis species carry endogenous FeLV sequences in their genome, a prerequisite for in situ development of recombinant and virulent FeLV strains [5,102,103,113].

To explore the origins and the unusual virulence of the emerging FeLV strain in pumas, Brown et al. [107] obtained infectious FeLV gene sequence (LTR and env genes; 2851 bp) from several FeLV-infected Florida panthers. Alignment and phylogenetic analysis of panther FeLV gene sequences and those from known domestic cat FeLV strains revealed three important aspects: (1) The panther FeLV was clearly aligned with FeLV domestic cat type FeLV-A, the strain that is largely avirulent until after recombination with endogenous sequences; (2) There was no evidence of endogenous FeLV sequences within in the panther FeLV; and (3) The panther FeLV was closely aligned with a highly virulent FeLV from domestic cats, FeLV-945. Although FeLV-9545 is considered an FeLV-A strain, it has a distinctive envelop and LTR sequence that are different from other FeLV-A strains. FeLV-945 is unusual is that its severe pathogenicity in domestic cats does not involve recombination with the endogenous FeLV sequences [114,115]. A vaccination campaign was initiated in 2006 and 52 Florida panthers were captured and vaccinated with no major FeLV incidence reported to date.

An interesting corollary to the Florida panther FeLV outbreak is that FIVPco is endemic in this population. Two distinctive strains were present in 2001, one from the original authentic Florida panther and a second accidentally introduced in 1995 from FIVPco infected Texas cougars. FIV incidence in the population was low (~15% in 1999–2000; [107]). By contrast, 13 of 17 panthers tested during 2004–2005 in the FeLV-endemic region (76%; Figure 1) were FIV positive [105,107]. This apparent elevation in FIV incidence among FeLV afflicted panthers raises the possibility of a role for FIV-mediated immune depletion in FeLV pathogenesis. In domestic cats, FIV and FeLV co-infections have resulted in conflicting interpretations [116,117,118,119,120,121].

The conclusion here is that domestic cat strains of viruses can cross species barriers with potentially devastating consequences to fragile wild populations of large felids. In this case, the requirement for endogenous FeLV recombination was abrogated and perhaps the resultant virulence was accelerated by FIV immune suppression in Florida panthers. As in lions, FIV depletes puma CD4-T lymphocytes [89], so the possibility of FIV accessory role is feasible. Unfortunately, a similar outbreak has recently occurred in wild populations of Iberian lynx [81], confirming that FeLV is capable of causing disease in non-domestic felids, contrary to conventional wisdom.

5. Conclusions

Early attempts to characterize the genetics, epidemiology and pathogenicity of feline viruses established the following accepted paradigms in viral disease: that fatal FIP resulted from a simple single mutation from the benign FCoV; that FIV was host-adapted and innocuous in non-domestic felids; and that FeLV-related disease could only occur in species within the domestic cat lineage and always resulted from recombination with endogenous FeLV. However, recent studies augmented by technological advances as well as increased surveillance of free-ranging cat species are revising these perceptions. FCoV strains may have different virulence, pathogenicity, and predisposition to FIP causing mutations; etiologies may be complex and different in different areas, cats may harbor multiple strains throughout their life, and diagnostic genetic profiles may someday be available. FIV in wild African lions, once considered benign, is causally linked with AIDS-related symptoms in some individuals, and some strains may increase susceptibility to co-infection and mortality. Fragile relic populations of Florida panther and Iberian lynx, once thought immune to domestic cat FeLV, are highly susceptible to certain strains that are able to emerge in new host species. Thus, several conventional paradigms have been unseated by recent studies of virus-host interactions in the wild.

Conflict of Interest

The authors declare no conflict of interest.

References and Notes

  1. Driscoll, C.A.; Macdonald, D.W.; O'Brien, S.J. From wild animals to domestic pets, an evolutionary view of domestication. Proc. Natl. Acad. Sci. U. S. A. 2009, 106, 9971–9978. [Google Scholar]
  2. WHO. Summary of probable SARS cases with onset of illness from 1 November 2002 to 31 July 2003. Available online: http://www.who.int/csr/sars/country/table2004_2004_2021/en/index.html (accessed on 16 January 2012).
  3. Hardy, W.D., Jr.; McClelland, A.J.; Zuckerman, E.E.; Snyder, H.W., Jr.; MacEwen, E.G.; Francis, D.; Essex, M. Development of virus non-producer lymphosarcomas in pet cats exposed to FeLv. Nature 1980, 288, 90–92. [Google Scholar]
  4. Pedersen, N.C.; Ho, E.W.; Brown, M.L.; Yamamoto, J.K. Isolation of a T-lymphotropic virus from domestic cats with an immunodeficiency-like syndrome. Science 1987, 235, 790–793. [Google Scholar]
  5. Mullins, J.I.; Hoover, E.A. Molecular aspects of feline leukemia virus pathogenesis. In Retrovirus Biology and Human Disease; Gallo, R.C., Wong-Staal, F., Eds.; Dekker: New York, NY, USA, 1990; pp. 87–116. [Google Scholar]
  6. Slattery, J.P.; Franchini, G.; Gessain, A. Genomic evolution, patterns of global dissemination, and interspecies transmission of human and simian T-cell leukemia/lymphotropic viruses. Genome Res. 1999, 9, 525–540. [Google Scholar]
  7. Troyer, J.L.; Pecon-Slattery, J.; Roelke, M.E.; Johnson, W.; VandeWoude, S.; Vazquez-Salat, N.; Brown, M.; Frank, L.; Woodroffe, R.; Winterbach, C.; et al. Seroprevalence and genomic divergence of circulating strains of feline immunodeficiency virus among Felidae and Hyaenidae species. J. Virol. 2005, 79, 8282–8294. [Google Scholar]
  8. O'Brien, S.J.; Nelson, G.W. Human genes that limit AIDS. Nat. Genet. 2004, 36, 565–574. [Google Scholar]
  9. Pedersen, N.C. A review of feline infectious peritonitis virus infection: 1963–2008. J. Feline Med. Surg. 2009, 11, 225–258. [Google Scholar]
  10. Eickmann, M.; Becker, S.; Klenk, H.D.; Doerr, H.W.; Stadler, K.; Censini, S.; Guidotti, S.; Masignani, V.; Scarselli, M.; Mora, M.; et al. Phylogeny of the SARS coronavirus. Science 2003, 302, 1504–1505. [Google Scholar]
  11. Ruscetti, S.K.; Turek, L.P.; Sherr, C.J. Three independent isolates of feline sarcoma virus code for three distinct gag-x polyproteins. J. Virol. 1980, 35, 259–264. [Google Scholar]
  12. Maeda, N.; Fan, H.; Yoshikai, Y. Oncogenesis by retroviruses: Old and new paradigms. Rev. Med. Virol. 2008, 18, 387–405. [Google Scholar]
  13. Harder, T.C.; Vahlenkamp, T.W. Influenza virus infections in dogs and cats. Vet. Immunol. Immunopathol. 2009, 134, 54–60. [Google Scholar]
  14. Van Kerkhove, M.D.; Mumford, E.; Mounts, A.W.; Bresee, J.; Ly, S.; Bridges, C.B.; Otte, J. Highly pathogenic avian influenza (H5N1): Pathways of exposure at the animal-human interface, a systematic review. PLoS One 2011, 6, e14582. [Google Scholar]
  15. Thiry, E.; Addie, D.; Belak, S.; Boucraut-Baralon, C.; Egberink, H.; Frymus, T.; Gruffydd-Jones, T.; Hartmann, K.; Hosie, M.J.; Lloret, A.; et al. Feline herpesvirus infection. ABCD guidelines on prevention and management. J. Feline Med. Surg. 2009, 11, 547–555. [Google Scholar]
  16. Winkler, I.G.; Flugel, R.M.; Lochelt, M.; Flower, R.L. Detection and molecular characterisation of feline foamy virus serotypes in naturally infected cats. Virology 1998, 247, 144–151. [Google Scholar]
  17. Meiering, C.D.; Linial, M.L. Historical perspective of foamy virus epidemiology and infection. Clin. Microbiol. Rev. 2001, 14, 165–176. [Google Scholar]
  18. Radford, A.D.; Coyne, K.P.; Dawson, S.; Porter, C.J.; Gaskell, R.M. Feline calicivirus. Vet. Res. 2007, 38, 319–335. [Google Scholar]
  19. Blanton, L.H.; Adams, S.M.; Beard, R.S.; Wei, G.; Bulens, S.N.; Widdowson, M.A.; Glass, R.I.; Monroe, S.S. Molecular and epidemiologic trends of caliciviruses associated with outbreaks of acute gastroenteritis in the United States, 2000–2004. J. Infect. Dis. 2006, 193, 413–421. [Google Scholar]
  20. Ikeda, Y.; Nakamura, K.; Miyazawa, T.; Takahashi, E.; Mochizuki, M. Feline host range of canine parvovirus: Recent emergence of new antigenic types in cats. Emerg. Infect. Dis. 2002, 8, 341–346. [Google Scholar]
  21. Brown, K.E. The expanding range of parvoviruses which infect humans. Rev. Med. Virol. 2010, 20, 231–244. [Google Scholar]
  22. Munson, L. Feline morbillivirus infection. In Infectious Diseases of Wild Animals; Williams, E.S., Barker, I.K., Eds.; Iowa State University Press: Ames, IA, USA, 2001; pp. 59–62. [Google Scholar]
  23. Rota, P.A.; Brown, K.; Mankertz, A.; Santibanez, S.; Shulga, S.; Muller, C.P.; Hubschen, J.M.; Siqueira, M.; Beirnes, J.; Ahmed, H.; et al. Global distribution of measles genotypes and measles molecular epidemiology. J. Infect. Dis. 2011, 204, S514–S523. [Google Scholar]
  24. Masters, P.S. The molecular biology of coronaviruses. Adv. Virus Res. 2006, 66, 193–292. [Google Scholar]
  25. Pedersen, N.C.; Evermann, J.F.; McKeirnan, A.J.; Ott, R.L. Pathogenicity studies of feline coronavirus isolates 79-1146 and 79-1683. Am. J. Vet. Res. 1984, 45, 2580–2585. [Google Scholar]
  26. de Groot, R.J. Feline infectous peritonitis. In The Coronoviridae; Siddell, S.G., Ed.; Plenum Press: New York, NY, USA, 1995; pp. 293–309. [Google Scholar]
  27. Addie, D.D. Clustering of feline coronaviruses in multicat households. Vet. J. 2000, 159, 8–9. [Google Scholar]
  28. Addie, D.D.; Jarrett, O. A study of naturally occurring feline coronavirus infections in kittens. Vet. Rec. 1992, 130, 133–137. [Google Scholar]
  29. Kennedy, M.; Citino, S.; McNabb, A.H.; Moffatt, A.S.; Gertz, K.; Kania, S. Detection of feline coronavirus in captive Felidae in the USA. J. Vet. Diagn. Invest. 2002, 14, 520–522. [Google Scholar]
  30. Foley, J.E.; Poland, A.; Carlson, J.; Pedersen, N.C. Patterns of feline coronavirus infection and fecal shedding from cats in multiple-cat environments. J. Am. Vet. Med. Assoc. 1997, 210, 1307–1312. [Google Scholar]
  31. Foley, J.E.; Poland, A.; Carlson, J.; Pedersen, N.C. Risk factors for feline infectious peritonitis among cats in multiple-cat environments with endemic feline enteric coronavirus. J. Am. Vet. Med. Assoc. 1997, 210, 1313–1318. [Google Scholar]
  32. Weiss, R.C.; Scott, F.W. Pathogenesis of feline infectious peritonitis: Nature and development of viremia. Am. J. Vet. Res. 1981, 42, 382–390. [Google Scholar]
  33. Kipar, A.; Kohler, K.; Leukert, W.; Reinacher, M. A comparison of lymphatic tissues from cats with spontaneous feline infectious peritonitis (FIP), cats with FIP virus infection but no FIP, and cats with no infection. J. Comp. Pathol. 2001, 125, 182–191. [Google Scholar] [CrossRef]
  34. Kipar, A.; Meli, M.L.; Failing, K.; Euler, T.; Gomes-Keller, M.A.; Schwartz, D.; Lutz, H.; Reinacher, M. Natural feline coronavirus infection: Differences in cytokine patterns in association with the outcome of infection. Vet. Immunol. Immunopathol. 2006, 112, 141–155. [Google Scholar]
  35. Rottier, P.J. The Coronavirus Membrane Glycoprotein. In The Coronaviridae; Siddell, S.G., Ed.; Plenum Press: New York, NY, USA, 1995; pp. 115–140. [Google Scholar]
  36. Poland, A.M.; Vennema, H.; Foley, J.E.; Pedersen, N.C. Two related strains of feline infectious peritonitis virus isolated from immunocompromised cats infected with a feline enteric coronavirus. J. Clin. Microbiol. 1996, 34, 3180–3184. [Google Scholar]
  37. Vennema, H.; Poland, A.; Foley, J.; Pedersen, N.C. Feline infectious peritonitis viruses arise by mutation from endemic feline enteric coronaviruses. Virology 1998, 243, 150–157. [Google Scholar]
  38. Addie, D.D.; Jarrett, J.O. Feline coronavirus antibodies in cats. Vet. Rec. 1992, 131, 202–203. [Google Scholar]
  39. Pedersen, N.C.; Black, J.W.; Boyle, J.F.; Evermann, J.F.; McKeirnan, A.J.; Ott, R.L. Pathogenic differences between various feline coronavirus isolates. Adv. Exp. Med. Biol. 1984, 173, 365–380. [Google Scholar]
  40. Pedersen, N.; Liu, H.; Dodd, K.A.; Pesavento, P.A. Significance of coronavirus mutants in feces and diseased tissues of cats suffering from feline infectious peritonitis. Viruses 2009, 1, 166–184. [Google Scholar] [CrossRef]
  41. Anishchenko, M.; Bowen, R.A.; Paessler, S.; Austgen, L.; Greene, I.P.; Weaver, S.C. Venezuelan encephalitis emergence mediated by a phylogenetically predicted viral mutation. Proc. Natl. Acad. Sci. U. S. A. 2006, 103, 4994–4999. [Google Scholar]
  42. Mongkolsapaya, J.; Dejnirattisai, W.; Xu, X.N.; Vasanawathana, S.; Tangthawornchaikul, N.; Chairunsri, A.; Sawasdivorn, S.; Duangchinda, T.; Dong, T.; Rowland-Jones, S.; et al. Original antigenic sin and apoptosis in the pathogenesis of dengue hemorrhagic fever. Nat. Med. 2003, 9, 921–927. [Google Scholar]
  43. Brown, M.A.; Troyer, J.L.; Pecon-Slattery, J.; Roelke, M.E.; O'Brien, S.J. Genetics and pathogenesis of feline infectious peritonitis virus. Emerg. Infect. Dis. 2009, 15, 1445–1452. [Google Scholar]
  44. Chang, H.W.; Egberink, H.F.; Rottier, P.J. Sequence analysis of feline coronaviruses and the circulating virulent/avirulent theory. Emerg. Infect. Dis. 2011, 17, 744–746. [Google Scholar]
  45. Norris, J.M.; Bosward, K.L.; White, J.D.; Baral, R.M.; Catt, M.J.; Malik, R. Clinicopathological findings associated with feline infectious peritonitis in Sydney, Australia: 42 cases (1990–2002). Aust. Vet. 2005, 83, 666–673. [Google Scholar] [CrossRef]
  46. Pesteanu-Somogyi, L.D.; Radzai, C.; Pressler, B.M. Prevalence of feline infectious peritonitis in specific cat breeds. J. Feline Med. Surg. 2006, 8, 1–5. [Google Scholar] [CrossRef]
  47. Olmsted, R.A.; Barnes, A.K.; Yamamoto, J.K.; Hirsch, V.M.; Purcell, R.H.; Johnson, P.R. Molecular cloning of feline immunodeficiency virus. Proc. Natl. Acad. Sci. U. S. A. 1989, 86, 2448–2452. [Google Scholar]
  48. Bendinelli, M.; Pistello, M.; Lombardi, S.; Poli, A.; Garzelli, C.; Matteucci, D.; Ceccherini-Nelli, L.; Malvaldi, G.; Tozzini, F. Feline immunodeficiency virus: An interesting model for AIDS studies and an important cat pathogen. Clin. Microbiol. Rev. 1995, 8, 87–112. [Google Scholar]
  49. Willett, B.J.; Flynn, J.N.; Hosie, M.J. FIV infection of the domestic cat: An animal model for AIDS. Immunol. Today 1997, 18, 182–189. [Google Scholar]
  50. Burkhard, M.J.; Dean, G.A. Transmission and immunopathogenesis of FIV in cats as a model for HIV. Curr. HIV Res. 2003, 1, 15–29. [Google Scholar]
  51. Sodora, D.L.; Shpaer, E.G.; Kitchell, B.E.; Dow, S.W.; Hoover, E.A.; Mullins, J.I. Identification of three feline immunodeficiency virus (FIV) env gene subtypes and comparison of the FIV and human immunodeficiency virus type 1 evolutionary patterns. J. Virol. 1994, 68, 2230–2238. [Google Scholar]
  52. Kakinuma, S.; Motokawa, K.; Hohdatsu, T.; Yamamoto, J.K.; Koyama, H.; Hashimoto, H. Nucleotide sequence of feline immunodeficiency virus: Classification of Japanese isolates into two subtypes which are distinct from non-Japanese subtypes. J. Virol. 1995, 69, 3639–3646. [Google Scholar]
  53. Carpenter, M.A.; Brown, E.W.; MacDonald, D.W.; O'Brien, S.J. Phylogeographic patterns of feline immunodeficiency virus genetic diversity in the domestic cat. Virology 1998, 251, 234–243. [Google Scholar]
  54. Hayward, J.J.; Rodrigo, A.G. Molecular epidemiology of feline immunodeficiency virus in the domestic cat (Felis catus). Vet. Immunol. Immunopathol. 2009, 134, 68–74. [Google Scholar]
  55. Pecoraro, M.R.; Tomonaga, K.; Miyazawa, T.; Kawaguchi, Y.; Sugita, S.; Tohya, Y.; Kai, C.; Etcheverrigaray, M.E.; Mikami, T. Genetic diversity of Argentine isolates of feline immunodeficiency virus. J. Gen. Virol. 1996, 77, 2031–2035. [Google Scholar]
  56. Johnson, W.E.; Eizirik, E.; Pecon-Slattery, J.; Murphy, W.J.; Antunes, A.; Teeling, E.; O'Brien, S.J. The late Miocene radiation of modern Felidae: A genetic assessment. Science 2006, 311, 73–77. [Google Scholar]
  57. Antunes, A.; Troyer, J.L.; Roelke, M.E.; Pecon-Slattery, J.; Packer, C.; Winterbach, C.; Winterbach, H.; Hemson, G.; Frank, L.; Stander, P.; et al. The evolutionary dynamics of the lion Panthera leo revealed by host and viral population genomics. PLoS Genet. 2008, 4, e1000251. [Google Scholar]
  58. Pecon-Slattery, J.; Troyer, J.L.; Johnson, W.E.; O'Brien, S.J. Evolution of feline immunodeficiency virus in Felidae: Implications for human health and wildlife ecology. Vet. Immunol. Immunopathol. 2008, 123, 32–44. [Google Scholar]
  59. Olmsted, R.A.; Langley, R.; Roelke, M.E.; Goeken, R.M.; Adger-Johnson, D.; Goff, J.P.; Albert, J.P.; Packer, C.; Laurenson, M.K.; Caro, T.M.; et al. Worldwide prevalence of lentivirus infection in wild feline species: Epidemiologic and phylogenetic aspects. J. Virol. 1992, 66, 6008–6018. [Google Scholar]
  60. Carpenter, M.A.; O'Brien, S.J. Coadaptation and immunodeficiency virus: Lessons from the Felidae. Curr. Opin. Genet. Dev. 1995, 5, 739–745. [Google Scholar]
  61. Carpenter, M.A.; Brown, E.W.; Culver, M.; Johnson, W.E.; Pecon-Slattery, J.; Brousset, D.; O'Brien, S.J. Genetic and phylogenetic divergence of feline immunodeficiency virus in the puma (Puma concolor). J. Virol. 1996, 70, 6682–6693. [Google Scholar]
  62. Franklin, S.P.; Troyer, J.L.; Terwee, J.A.; Lyren, L.M.; Boyce, W.M.; Riley, S.P.; Roelke, M.E.; Crooks, K.R.; Vandewoude, S. Frequent transmission of immunodeficiency viruses among bobcats and pumas. J. Virol. 2007, 81, 10961–10969. [Google Scholar]
  63. VandeWoude, S.; Apetrei, C. Going wild: Lessons from naturally occurring T-lymphotropic lentiviruses. Clin. Microbiol. Rev. 2006, 19, 728–762. [Google Scholar]
  64. Troyer, J.L.; Vandewoude, S.; Pecon-Slattery, J.; McIntosh, C.; Franklin, S.; Antunes, A.; Johnson, W.; O'Brien, S.J. FIV cross-species transmission: An evolutionary prospective. Vet. Immunol. Immunopathol. 2008, 123, 159–166. [Google Scholar]
  65. Pecon-Slattery, J.; McCracken, C.L.; Troyer, J.L.; VandeWoude, S.; Roelke, M.; Sondgeroth, K.; Winterbach, C.; Winterbach, H.; O'Brien, S.J. Genomic organization, sequence divergence, and recombination of feline immunodeficiency virus from lions in the wild. BMC Genom. 2008, 9, 66. [Google Scholar]
  66. Olmsted, R.A.; Hirsch, V.M.; Purcell, R.H.; Johnson, P.R. Nucleotide sequence analysis of feline immunodeficiency virus: Genome organization and relationship to other lentiviruses. Proc. Natl. Acad. Sci. U. S. A. 1989, 86, 8088–8092. [Google Scholar]
  67. Langley, R.J.; Hirsch, V.M.; O'Brien, S.J.; Adger-Johnson, D.; Goeken, R.M.; Olmsted, R.A. Nucleotide sequence analysis of puma lentivirus (PLV-14): Genomic organization and relationship to other lentiviruses. Virology 1994, 202, 853–864. [Google Scholar]
  68. Barr, M.C.; Zou, L.; Long, F.; Hoose, W.A.; Avery, R.J. Proviral organization and sequence analysis of feline immunodeficiency virus isolated from a Pallas' cat. Virology 1997, 228, 84–91. [Google Scholar]
  69. Ostrowski, S.; Van Vuuren, M.; Lenain, D.M.; Durand, A. A serologic survey of wild felids from central west Saudi Arabia. J. Wildl. Dis. 2003, 39, 696–701. [Google Scholar]
  70. Leutenegger, C.M.; Hofmann-Lehmann, R.; Riols, C.; Liberek, M.; Worel, G.; Lups, P.; Fehr, D.; Hartmann, M.; Weilenmann, P.; Lutz, H. Viral infections in free-living populations of the European wildcat. J. Wildl. Dis. 1999, 35, 678–686. [Google Scholar]
  71. Daniels, M.J.; Golder, M.C.; Jarrett, O.; MacDonald, D.W. Feline viruses in wildcats from Scotland. J. Wildl. Dis. 1999, 35, 121–124. [Google Scholar]
  72. Fromont, E.; Sager, A.; Leger, F.; Bourguemestre, F.; Jouquelet, E.; Stahl, P.; Pontier, D.; Artois, M. Prevalence and pathogenicity of retroviruses in wildcats in France. Vet. Rec. 2000, 146, 317–319. [Google Scholar]
  73. Nishimura, Y.; Goto, Y.; Yoneda, K.; Endo, Y.; Mizuno, T.; Hamachi, M.; Maruyama, H.; Kinoshita, H.; Koga, S.; Komori, M.; et al. Interspecies transmission of feline immunodeficiency virus from the domestic cat to the Tsushima cat (Felis bengalensis euptilura) in the wild. J. Virol. 1999, 73, 7916–7921. [Google Scholar]
  74. Nakamura, K.; Miyazawa, T.; Ikeda, Y.; Sato, E.; Nishimura, Y.; Nguyen, N.T.; Takahashi, E.; Mochizuki, M.; Mikami, T. Contrastive prevalence of feline retrovirus infections between northern and southern Vietnam. J. Vet. Med. Sci. 2000, 62, 921–923. [Google Scholar]
  75. Lutz, H.; Isenbugel, E.; Lehmann, R.; Sabapara, R.H.; Wolfensberger, C. Retrovirus infections in non-domestic felids: Serological studies and attempts to isolate a lentivirus. Vet. Immunol. Immunopathol. 1992, 35, 215–224. [Google Scholar]
  76. Franklin, S.P.; Troyer, J.L.; Terwee, J.A.; Lyren, L.M.; Kays, R.W.; Riley, S.P.; Boyce, W.M.; Crooks, K.R.; Vandewoude, S. Variability in assays used for detection of lentiviral infection in bobcats (Lynx rufus), pumas (Puma concolor), and ocelots (Leopardus pardalis). J. Wildl. Dis. 2007, 43, 700–710. [Google Scholar]
  77. Biek, R.; Rodrigo, A.G.; Holley, D.; Drummond, A.; Anderson, C.R., Jr.; Ross, H.A.; Poss, M. Epidemiology, genetic diversity, and evolution of endemic feline immunodeficiency virus in a population of wild cougars. J. Virol. 2003, 77, 9578–9589. [Google Scholar]
  78. Blanco, K.; Peña, R.; Hernández, C.; Jiménez, M.; Araya, L.N.; Romero, J.J.; Dolz, G. Serological detection of viral infections in captive wild cats from Costa Rica. Vet. Med. Int. 2011, 2011, 879029. [Google Scholar]
  79. Thalwitzer, S.; Wachter, B.; Robert, N.; Wibbelt, G.; Muller, T.; Lonzer, J.; Meli, M.L.; Bay, G.; Hofer, H.; Lutz, H. Seroprevalences to viral pathogens in free-ranging and captive cheetahs (Acinonyx jubatus) on Namibian Farmland. Clin. Vaccine Immunol. 2009, 17, 232–238. [Google Scholar]
  80. Osofsky, S.A.; Hirsch, K.J.; Zuckerman, E.E.; et al. Feline lentivirus and feline oncovirus status of free-ranging lions (Panthera leo), leopards (Panthera pardus), and cheetahs (Acinonyx jubatus) in Botswana: A regional perspective. J. Zoo wildl. Med. 1996, 27, 453–467. [Google Scholar]
  81. Meli, M.L.; Cattori, V.; Martinez, F.; Lopez, G.; Vargas, A.; Simon, M.A.; Zorrilla, I.; Munoz, A.; Palomares, F.; Lopez-Bao, J.V.; et al. Feline leukemia virus and other pathogens as important threats to the survival of the critically endangered Iberian lynx (Lynx pardinus). PLoS One 2009, 4, e4744. [Google Scholar]
  82. Biek, R.; Zarnke, R.L.; Gillin, C.; Wild, M.; Squires, J.R.; Poss, M. Serologic survey for viral and bacterial infections in western populations of Canada lynx (Lynx canadensis). J. Wildl. Dis. 2002, 38, 840–845. [Google Scholar]
  83. Franklin, S.P.; Kays, R.W.; Moreno, R.; TerWee, J.A.; Troyer, J.L.; VandeWoude, S. Ocelots on Barro Colorado Island are infected with feline immunodeficiency virus but not other common feline and canine viruses. J. Wildl. Dis. 2008, 44, 760–765. [Google Scholar]
  84. Brennan, G.; Podell, M.D.; Wack, R.; Kraft, S.; Troyer, J.L.; Bielefeldt-Ohmann, H.; VandeWoude, S. Neurologic disease in captive lions (Panthera leo) with low-titer lion lentivirus infection. J. Clin. Microbiol. 2006, 44, 4345–4352. [Google Scholar]
  85. Driciru, M.; Siefert, L.; Prager, K.C.; Dubovi, E.; Sande, R.; Princee, F.; Friday, T.; Munson, L. A serosurvey of viral infections in lions (Panthera leo), from Queen Elizabeth National Park, Uganda. J. Wildl. Dis. 2006, 42, 667–671. [Google Scholar]
  86. Adams, H.; van Vuuren, M.; Kania, S.; Bosman, A.M.; Keet, D.; New, J.; Kennedy, M. Sensitivity and specificity of a nested polymerase chain reaction for detection of lentivirus infection in lions (Panthera leo). J. Zoo Wildl. Med. 2011, 41, 608–615. [Google Scholar]
  87. Packer, C.; Altizer, S.; Appel, M.; Brown, E.; Martenson, J.; O’Brien, S.J.; Roelke-Parker, M.; Hofmann-Lehmann, R.; Lutz, H. Viruses of the Serengeti: Patterns of infection and mortality in African lions. J. Anim. Ecol. 1999, 68, 1161–1178. [Google Scholar]
  88. Roelke, M.E.; Brown, M.A.; Troyer, J.L.; Winterbach, H.; Winterbach, C.; Hemson, G.; Smith, D.; Johnson, R.C.; Pecon-Slattery, J.; Roca, A.L.; et al. Pathological manifestations of feline immunodeficiency virus (FIV) infection in wild African lions. Virology 2009, 390, 1–12. [Google Scholar]
  89. Roelke, M.E.; Pecon-Slattery, J.; Taylor, S.; Citino, S.; Brown, E.; Packer, C.; Vandewoude, S.; O'Brien, S.J. T-lymphocyte profiles in FIV-infected wild lions and pumas reveal CD4 depletion. J. Wildl. Dis. 2006, 42, 234–248. [Google Scholar]
  90. Keele, B.F.; Jones, J.H.; Terio, K.A.; Estes, J.D.; Rudicell, R.S.; Wilson, M.L.; Li, Y.; Learn, G.H.; Beasley, T.M.; Schumacher-Stankey, J.; et al. Increased mortality and AIDS-like immunopathology in wild chimpanzees infected with SIVcpz. Nature 2009, 460, 515–519. [Google Scholar]
  91. Roelke-Parker, M.E.; Munson, L.; Packer, C.; Kock, R.; Cleaveland, S.; Carpenter, M.; O'Brien, S.J.; Pospischil, A.; Hofmann-Lehmann, R.; Lutz, H.; et al. A canine distemper virus epidemic in Serengeti lions (Panthera leo). Nature 1996, 379, 441–445. [Google Scholar]
  92. Brown, E.W.; Yuhki, N.; Packer, C.; O'Brien, S.J. A lion lentivirus related to feline immunodeficiency virus: Epidemiologic and phylogenetic aspects. J. Virol. 1994, 68, 5953–5968. [Google Scholar]
  93. Troyer, J.L.; Pecon-Slattery, J.; Roelke, M.E.; Black, L.; Packer, C.; O'Brien, S.J. Patterns of feline immunodeficiency virus multiple infection and genome divergence in a free-ranging population of African lions. J. Virol. 2004, 78, 3777–3791. [Google Scholar]
  94. Troyer, J.L.; Roelke, M.E.; Jespersen, J.M.; Baggett, N.; Buckley-Beason, V.; Macnulty, D.; Craft, M.; Packer, C.; Pecon-Slattery, J.; O'Brien, S.J. FIV diversity: FIV(Ple) subtype composition may influence disease outcome in African lions. Vet. Immunol. Immunopathol. 2011, 143, 338–346. [Google Scholar]
  95. VandeWoude, S.; Hageman, C.A.; O'Brien, S.J.; Hoover, E.A. Nonpathogenic lion and puma lentiviruses impart resistance to superinfection by virulent feline immunodeficiency virus. J. Acquir. Immune Defic. Syndr. 2002, 29, 1–10. [Google Scholar]
  96. VandeWoude, S.; Hageman, C.L.; Hoover, E.A. Domestic cats infected with lion or puma lentivirus develop anti-feline immunodeficiency virus immune responses. J. Acquir. Immune Defic. Syndr. 2003, 34, 20–31. [Google Scholar]
  97. Terwee, J.A.; Carlson, J.K.; Sprague, W.S.; Sondgeroth, K.S.; Shropshire, S.B.; Troyer, J.L.; VandeWoude, S. Prevention of immunodeficiency virus induced CD4+ T-cell depletion by prior infection with a non-pathogenic virus. Virology 2008, 377, 63–70. [Google Scholar]
  98. Jarrett, W.F.; Crawford, E.M.; Martin, W.B.; Davie, F. A Virus-Like Particle Associated with Leukemia (Lymphosarcoma). Nature 1964, 202, 567–569. [Google Scholar]
  99. Hardy, W.D. The virology, immunology and epidemiology of the feline leukemia virus. In Feline Leukemia Virus; Hardy, W.D., Essex, M., McClelland, A.J., Eds.; Elsevier/North-Holland: New York, NY, USA, 1980; pp. 33–78. [Google Scholar]
  100. Overbaugh, J.; Bangham, C.R. Selection forces and constraints on retroviral sequence variation. Science 2001, 292, 1106–1109. [Google Scholar]
  101. Phipps, A.J.; Chen, H.; Hayes, K.A.; Roy-Burman, P.; Mathes, L.E. Differential pathogenicity of two feline leukemia virus subgroup A molecular clones, pFRA and pF6A. J. Virol. 2000, 74, 5796–5801. [Google Scholar]
  102. Neil, J.C.; Fulton, R.; Rigby, M.; Stewart, M. Feline leukaemia virus: Generation of pathogenic and oncogenic variants. Curr. Top. Microbiol. Immunol. 1991, 171, 67–93. [Google Scholar]
  103. Stewart, M.A.; Warnock, M.; Wheeler, A.; Wilkie, N.; Mullins, J.I.; Onions, D.E.; Neil, J.C. Nucleotide sequences of a feline leukemia virus subgroup A envelope gene and long terminal repeat and evidence for the recombinational origin of subgroup B viruses. J. Virol. 1986, 58, 825–834. [Google Scholar]
  104. Benveniste, R.E.; Sherr, C.J.; Todaro, G.J. Evolution of type C viral genes: Origin of feline leukemia virus. Science 1975, 190, 886–888. [Google Scholar]
  105. Cunningham, M.W.; Brown, M.A.; Shindle, D.B.; Terrell, S.P.; Hayes, K.A.; Ferree, B.C.; McBride, R.T.; Blankenship, E.L.; Jansen, D.; Citino, S.B.; et al. Epizootiology and management of feline leukemia virus in the Florida puma. J. Wildl. Dis. 2008, 44, 537–552. [Google Scholar]
  106. Kennedy-Stoskopf, S. Emerging viral infections in large cats. In Zoo and Wild Animal Medicine; Fowler, M.E., Miller, R.E., Eds.; W.B. Saunders: Philadelphia, PA, USA, 1999; pp. 401–410. [Google Scholar]
  107. Brown, M.A.; Cunningham, M.W.; Roca, A.L.; Troyer, J.L.; Johnson, W.E.; O'Brien, S.J. Genetic characterization of feline leukemia virus from Florida panthers. Emerg. Infect. Dis. 2008, 14, 252–259. [Google Scholar]
  108. Young, S.P.; Goldman, A. The Puma, Mysterious American Cat; Dover Publications: New York, NY, USA, 1946; p. 358. [Google Scholar]
  109. Nowak, R.M.; McBride, R. Status survey of the Florida panther. In World Wildlife Fund Yearbook 1973–1974; Danbury Press: Danbury, CT, USA, 1974; pp. 112–113. [Google Scholar]
  110. Johnson, W.E.; Onorato, D.P.; Roelke, M.E.; Land, E.D.; Cunningham, M.; Belden, R.C.; McBride, R.; Jansen, D.; Lotz, M.; Shindle, D.; et al. Genetic restoration of the Florida panther. Science 2010, 329, 1641–1645. [Google Scholar]
  111. Seal, U.S. A Plan for Genetic Restoration and Management of the Florida Panther (Felis concolor coryi).; White Oak Conservation Center: Yulee, FL, USA, 1994; p. 23. [Google Scholar]
  112. McBride, R. The Documented Panther Population (DPP) and Its Current Distribution from July 1, 2002 to June 30, 2003; Livestock Protection Company: Alpine, TA, USA, 2003; p. 11. [Google Scholar]
  113. Benveniste, R.E.; Todaro, G.J. Segregation of RD-114 AND FeL-V-related sequences in crosses between domestic cat and leopard cat. Nature 1975, 257, 506–508. [Google Scholar]
  114. Chandhasin, C.; Coan, P.N.; Pandrea, I.; Grant, C.K.; Lobelle-Rich, P.A.; Puetter, A.; Levy, L.S. Unique long terminal repeat and surface glycoprotein gene sequences of feline leukemia virus as determinants of disease outcome. J. Virol. 2005, 79, 5278–5287. [Google Scholar]
  115. Chandhasin, C.; Coan, P.N.; Levy, L.S. Subtle mutational changes in the SU protein of a natural feline leukemia virus subgroup A isolate alter disease spectrum. J. Virol. 2005, 79, 1351–1360. [Google Scholar]
  116. Lee, I.T.; Levy, J.K.; Gorman, S.P.; Crawford, P.C.; Slater, M.R. Prevalence of feline leukemia virus infection and serum antibodies against feline immunodeficiency virus in unowned free-roaming cats. J. Am. Vet. Med. Assoc. 2002, 220, 620–622. [Google Scholar]
  117. O'Connor, T.P., Jr.; Tonelli, Q.J.; Scarlett, J.M. Report of the National FeLV/FIV Awareness Project. J. Am. Vet. Med. Assoc. 1991, 199, 1348–1353. [Google Scholar]
  118. Ishida, T.; Washizu, T.; Toriyabe, K.; Motoyoshi, S.; Tomoda, I.; Pedersen, N.C. Feline immunodeficiency virus infection in cats of Japan. J. Am. Vet. Med. Assoc. 1989, 194, 221–225. [Google Scholar]
  119. O'Connor, T.P., Jr.; Tanguay, S.; Steinman, R.; Smith, R.; Barr, M.C.; Yamamoto, J.K.; Pedersen, N.C.; Andersen, P.R.; Tonelli, Q.J. Development and evaluation of immunoassay for detection of antibodies to the feline T-lymphotropic lentivirus (feline immunodeficiency virus). J. Clin. Microbiol. 1989, 27, 474–479. [Google Scholar]
  120. Yamamoto, J.K.; Hansen, H.; Ho, E.W.; Morishita, T.Y.; Okuda, T.; Sawa, T.R.; Nakamura, R.M.; Pedersen, N.C. Epidemiologic and clinical aspects of feline immunodeficiency virus infection in cats from the continental United States and Canada and possible mode of transmission. J. Am. Vet. Med. Assoc. 1989, 194, 213–220. [Google Scholar]
  121. Cohen, N.D.; Carter, C.N.; Thomas, M.A.; Lester, T.L.; Eugster, A.K. Epizootiologic association between feline immunodeficiency virus infection and feline leukemia virus seropositivity. J. Am. Vet. Med. Assoc. 1990, 197, 220–225. [Google Scholar]
Viruses EISSN 1999-4915 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert