Special Issue "Comparative Studies on HIV and FIV in Animals and Humans"

A special issue of Veterinary Sciences (ISSN 2306-7381).

Deadline for manuscript submissions: closed (1 December 2016)

Special Issue Editors

Guest Editor
Prof. Dr. Rick Meeker PhD

Department of Neurology, School of Medicine, University of North Carolina at Chapel Hill, 170 Manning Drive, Chapel Hill, NC 27599, USA
Website | E-Mail
Interests: feline immunodeficiency virus; human immunodeficiency virus; inflammation; neurodegeneration; macrophages; microglia
Guest Editor
Dr. Jonathan Fogle DVM, PhD, DACVIM

Comparative Immunology Research Laboratory, College of Veterinary Medicine, NC State University, 1060 William Moore Drive, Raleigh, NC 27607, USA
Website | E-Mail
Interests: comparative immunology; animal models; regulatory T cells; CD8+ T cells; lymphocyte epigenetics

Special Issue Information

Dear Colleagues,

Animal models are essential components of efforts devoted to the development of treatments for diseases and injury for both human and veterinary medicine. This is clearly demonstrated for feline immunodeficiency virus (FIV), where research has not only led to the development of a vaccine effective against heterologous virus challenge, but also has provided a wealth of information on retroviral biology, immunology and neuro-immune interactions relevant to humans infected with human immunodeficiency virus (HIV). The success of efforts focused on the development of interventions for human diseases depends not only on the unique information provided by animal models but also on successful translation of findings from animal studies to humans. The melding of veterinary and human medicine is essential to the process but often receives too little attention leading to costly, inefficient and often-ineffective development strategies. In this Special Issue, “Comparative Studies on HIV and FIV in Animals and Humans”, original articles and short communications will highlight cutting-edge lentiviral research focusing on translational applications. As a complement to original research, several mini-reviews discussing contributions and limitations of the FIV model to our understanding of retroviral pathogenesis will be included. We are excited about this opportunity to present recent advances using this important translational model.

Rick Meeker, PhD
Jonathan Fogle, DVM, PhD, DACVIM
Guest Editors

Manuscript Submission Information

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Keywords

  • animal models
  • immune deficiency
  • immune activation
  • FIV
  • Retrovirus
  • Inflammation
  • nervous system
  • dementia
  • vaccine
  • immune regulation

Published Papers (6 papers)

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Research

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Open AccessArticle Felis Catus Gammaherpesvirus 1 DNAemia in Whole Blood from Therapeutically Immunosuppressed or Retrovirus-Infected Cats
Vet. Sci. 2017, 4(1), 16; doi:10.3390/vetsci4010016
Received: 17 January 2017 / Revised: 21 February 2017 / Accepted: 10 March 2017 / Published: 14 March 2017
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Abstract
Gammaherpesviruses are major co-pathogens of human immunodeficiency virus (HIV) infection, making the interactions between feline immunodeficiency virus (FIV) and Felis catus gammaherpesvirus 1 (FcaGHV1) pertinent to both human and veterinary medical research. FIV-infected cats are at increased risk of FcaGHV1 DNAemia and consistently
[...] Read more.
Gammaherpesviruses are major co-pathogens of human immunodeficiency virus (HIV) infection, making the interactions between feline immunodeficiency virus (FIV) and Felis catus gammaherpesvirus 1 (FcaGHV1) pertinent to both human and veterinary medical research. FIV-infected cats are at increased risk of FcaGHV1 DNAemia and consistently harbor higher FcaGHV1 loads than FIV-uninfected cats. Whether immune deficiencies unrelated to FIV are associated with similar risks is unknown. Using whole blood FcaGHV1 qPCR, we found no difference in the frequency of DNAemia or DNA load in therapeutically immunosuppressed (P1, n = 18) or feline leukemia virus (FeLV)-infected (P2, n = 57) patients compared with age- and sex-matched controls (C1, n = 58; C2, n = 57). In contrast, FIV/FeLV-co-infected cats (P3, n = 5) were at increased risk of FcaGHV1 DNAemia compared to retrovirus uninfected controls (C3, n = 39; p = 0.0068), and had a higher median FcaGHV1 DNA load, although the latter was not significant. FIV/FeLV-co-infected cats (P3) had a similar frequency of FcaGHV1 DNAemia reported compared to FIV-infected controls (C4). In conclusion, we found no evidence that cats with therapeutic immunosuppression or FeLV infection were at greater risk of FcaGHV1 DNAemia or had higher FcaGHV1 DNA load in whole blood. The risk of DNAemia in FIV/FeLV-co-infected cats was similar to that documented previously in cats infected with FIV alone. Full article
(This article belongs to the Special Issue Comparative Studies on HIV and FIV in Animals and Humans)
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Open AccessArticle Micro-RNA 10a Is Increased in Feline T Regulatory Cells and Increases Foxp3 Protein Expression Following In Vitro Transfection
Vet. Sci. 2017, 4(1), 12; doi:10.3390/vetsci4010012
Received: 4 November 2016 / Revised: 25 January 2017 / Accepted: 17 February 2017 / Published: 21 February 2017
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Abstract
CD4+CD25+Foxp3+ T regulatory (Treg) cells are activated during the course of lentiviral infection and exhibit heightened suppressor function when compared to Treg cells from uninfected controls. Foxp3 is essential to Treg cell function and multiple studies have documented
[...] Read more.
CD4+CD25+Foxp3+ T regulatory (Treg) cells are activated during the course of lentiviral infection and exhibit heightened suppressor function when compared to Treg cells from uninfected controls. Foxp3 is essential to Treg cell function and multiple studies have documented that lentivirus-activated Treg cells exhibit heightened Foxp3 expression when compared to Treg cells from uninfected controls. Our hypothesis was that lentivirus-induced micro-RNAs (miRNAs) contribute to heightened Treg cell suppressor function by stabilizing Foxp3 expression. We demonstrated that CD4+CD25+ T cells from both feline immunodeficiency virus infected (FIV+) cats and uninfected control cats exhibit increased miRNA 10a and 21 levels compared to autologous CD4+CD25 T cells but there was no difference in the levels of these miRNAs when Treg cells from FIV+ cats were compared to Treg cells from uninfected controls. Further, there was no increase in Foxp3 mRNA following transfection of miRNA 10a or 21 into a feline cell line. However, transfection with miRNA 10a resulted in increased Foxp3 protein expression. Full article
(This article belongs to the Special Issue Comparative Studies on HIV and FIV in Animals and Humans)
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Open AccessArticle Sequence Instability in the Proviral Long Terminal Repeat and gag Regions from Peripheral Blood and Tissue-Derived Leukocytes of FIV-Infected Cats during the Late Asymptomatic Phase
Vet. Sci. 2016, 3(2), 10; doi:10.3390/vetsci3020010
Received: 17 March 2016 / Revised: 23 May 2016 / Accepted: 2 June 2016 / Published: 6 June 2016
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Abstract
Feline immunodeficiency virus (FIV) infection results in viral persistence, a prolonged asymptomatic phase, and progressive immunopathology. During the asymptomatic phase, a cohort of experimentally FIV-infected cats exhibits features of viral latency in blood suggestive of inactive viral replication. We sought to investigate viral
[...] Read more.
Feline immunodeficiency virus (FIV) infection results in viral persistence, a prolonged asymptomatic phase, and progressive immunopathology. During the asymptomatic phase, a cohort of experimentally FIV-infected cats exhibits features of viral latency in blood suggestive of inactive viral replication. We sought to investigate viral replication activity and genomic stability of the FIV proviral long terminal repeat (LTR) and the 5′ aspect of gag over time. FIV-infected cats during the asymptomatic phase demonstrated undetectable plasma FIV gag RNA transcripts and intermittent to undetectable blood-derived cell-associated FIV gag RNA. The LTR sequence demonstrated instability in blood-derived cells over time, in spite of low to undetectable viral replication. Sequence variation in the LTR was identified in CD4+ and CD21+ leukocytes from blood and surgically removed lymph nodes. Three single nucleotide polymorphisms (SNPs) in the LTR were commonly identified. Promoter functionality of a common LTR SNP and rare U3 mutation were examined by reporter gene assays and demonstrated either no change or increased basal FIV promoter function, respectively. In conclusion, this cohort of asymptomatic FIV-infected cats demonstrated instability of the LTR and 5’ gag sequences during the study period, in spite of undetectable plasma and rare to undetectable viral gag RNA, which suggests that blood may not accurately represent viral activity in asymptomatic FIV-infected cats. Full article
(This article belongs to the Special Issue Comparative Studies on HIV and FIV in Animals and Humans)
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Review

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Open AccessReview Feline Immunodeficiency Virus Neuropathogenesis: A Model for HIV-Induced CNS Inflammation and Neurodegeneration
Vet. Sci. 2017, 4(1), 14; doi:10.3390/vetsci4010014
Received: 12 January 2017 / Revised: 22 February 2017 / Accepted: 1 March 2017 / Published: 6 March 2017
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Abstract
Feline Immunodeficiency virus (FIV), similar to its human analog human immunodeficiency virus (HIV), enters the central nervous system (CNS) soon after infection and establishes a protected viral reservoir. The ensuing inflammation and damage give rise to varying degrees of cognitive decline collectively known
[...] Read more.
Feline Immunodeficiency virus (FIV), similar to its human analog human immunodeficiency virus (HIV), enters the central nervous system (CNS) soon after infection and establishes a protected viral reservoir. The ensuing inflammation and damage give rise to varying degrees of cognitive decline collectively known as HIV-associated neurocognitive disorders (HAND). Because of the similarities to HIV infection and disease, FIV has provided a useful model for both in vitro and in vivo studies of CNS infection, inflammation and pathology. This mini review summarizes insights gained from studies of early infection, immune cell trafficking, inflammation and the mechanisms of neuropathogenesis. Advances in our understanding of these processes have contributed to the development of therapeutic interventions designed to protect neurons and regulate inflammatory activity. Full article
(This article belongs to the Special Issue Comparative Studies on HIV and FIV in Animals and Humans)
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Open AccessReview The Comparative Value of Feline Virology Research: Can Findings from the Feline Lentiviral Vaccine Be Translated to Humans?
Vet. Sci. 2017, 4(1), 7; doi:10.3390/vetsci4010007
Received: 13 December 2016 / Revised: 17 January 2017 / Accepted: 24 January 2017 / Published: 28 January 2017
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Abstract
Feline immunodeficiency virus (FIV) is a lentivirus of domestic cats that shares several similarities with its human counterpart, human immunodeficiency virus (HIV). Their analogies include genomic organization, lymphocyte tropism, viral persistence and induction of immunodeficiency. FIV is the only lentivirus for which a
[...] Read more.
Feline immunodeficiency virus (FIV) is a lentivirus of domestic cats that shares several similarities with its human counterpart, human immunodeficiency virus (HIV). Their analogies include genomic organization, lymphocyte tropism, viral persistence and induction of immunodeficiency. FIV is the only lentivirus for which a commercial vaccine is registered for prevention in either human or veterinary medicine. This provides a unique opportunity to investigate the mechanisms of protection induced by lentivirus vaccines at the population level and might contribute to the development of efficacious HIV vaccines. As well as having comparative value for vaccine studies, FIV research has shed some light on the relationship between lentiviral tropism and pathogenesis. Recent studies in our laboratory demonstrated that the interaction between FIV and its primary receptor changes as disease progresses, reminiscent of the receptor switch observed as disease progresses in HIV infected individuals. Here we summarise findings illustrating that, in addition to its veterinary significance, FIV has comparative value, providing a useful model to explore lentivirus–host interactions and to examine potential immune correlates of protection against HIV infection. Full article
(This article belongs to the Special Issue Comparative Studies on HIV and FIV in Animals and Humans)
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Open AccessReview The Use of Recombinant Feline Interferon Omega Therapy as an Immune-Modulator in Cats Naturally Infected with Feline Immunodeficiency Virus: New Perspectives
Vet. Sci. 2016, 3(4), 32; doi:10.3390/vetsci3040032
Received: 28 July 2016 / Revised: 18 October 2016 / Accepted: 25 October 2016 / Published: 27 October 2016
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Abstract
Type I interferons (IFNs) are well-known cytokines that, among their main functions, are key components of the host immune response against viral infections. Due to its immune modulation properties, they are commonly used in the therapeutic approach of various retroviral infections, namely human
[...] Read more.
Type I interferons (IFNs) are well-known cytokines that, among their main functions, are key components of the host immune response against viral infections. Due to its immune modulation properties, they are commonly used in the therapeutic approach of various retroviral infections, namely human immunodeficiency virus (HIV) and feline immunodeficiency virus (FIV). In HIV infection, it has been shown that IFN therapy limits early viral replication, particularly useful on post-exposure prophylaxis. In veterinary medicine, recombinant feline interferon omega (rFeIFN-ω) was the first interferon licensed for use in cats. Several studies have recently shown that this compound seems to stimulate the innate immunity, decreasing clinical signs and co-infections in naturally FIV-infected cats. More than summarizing the main conclusions about rFeIFN-ω in cats, this review emphasizes the immune-modulation properties of IFN therapy, opening new perspectives for its use in retroviral infections. Either in FIV-infected cats or in HIV individuals, type I IFNs seem to induce an innate immune-modulation and should not be overlooked as a therapeutic option in retroviral infections. Full article
(This article belongs to the Special Issue Comparative Studies on HIV and FIV in Animals and Humans)

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