Special Issue "Small Ruminant Lentiviruses"

Guest Editor
Prof. Dr. Esperanza Gómez-Lucía
Grupo Retrovirus Animales, Dpto. Sanidad Animal, Facultad de Veterinaria – Universidad Complutense Madrid, 28040 Madrid, Spain
Website: http://www.ucm.es/centros/webs/gi5035/
E-Mail: duato@vet.ucm.es
Phone: +34 91 394 3718

Guest Editor
Prof. Dr. Brian G. Murphy
Department of Pathology, Microbiology & Immunology, School of Veterinary Medicine, University of California, Davis, 4206 Vet Med 3A, Davis, CA 95616, USA
Website: http://faculty.vetmed.ucdavis.edu/faculty/bmurphy/
E-Mail: bmurphy@ucdavis.edu
Phone: +1 530 752 9011

Guest Editor
Prof. Dr. Ana Domenech
Grupo Retrovirus Animales, Dpto. Sanidad Animal, Facultad de Veterinaria – Universidad Complutense Madrid, 28040 Madrid, Spain
Website: http://www.ucm.es/centros/webs/gi5035/
E-Mail: domenech@vet.ucm.es
Phone: +34 91 394 4087

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Type of Paper: Review
Title: Small Ruminant Lentiviruses (SRLVs): What do we Know and What we Should Know?
Authors: Juliano Cesar Minardi, Dinesh Kumar Singh, Ali Lamara and Yahia Chebloune *
Affiliation: Corresponding Author: Laboratory Virus Pathogenesis and Vaccination, University Joseph Fourier, Grenoble, France. Tel +33476637123; Fax +33476637497 E-Mail: ychebloune@lyon.inra.fr
Abstract: Zoonotic transmission events of simian immunodeficiency virus (SIV) from non-human primates to humans have generated the acquired immunodeficiency syndrome (AIDS), one of the most devastating infectious disease of the last century with more than 30 million people died and about 40.3 million people currently infected worldwide. Human immunodeficiency virus (HIV-1 and HIV-2) the two major viruses that cause AIDS, are retroviruses of the lentivirus genus. The genus includes arthritis-encephalitis virus (CAEV) and maedi-visna virus (MVV) a heterogeneous group of viruses named small ruminant lentiviruses (SRLVs), affecting goat and sheep and responsible for chronic multisytemic inflammatory disease in their host species. Lentivirus genome integrates into the host DNA, causing persistent infection and due to their error-prone reverse transcriptase; display a remarkable diversity presenting a high mutation and recombination rate during viral replication.  Direct evidence of mixed infections under field conditions with these two closely related SRLVs was found, as suggested by detection of some subtypes in both sheep and goats. The evidence of a genetic continuum with caprine and ovine field isolates from various geographical areas that did not simply clustered according to the animal species they were isolated from, demonstrates the absence of an efficient species barrier preventing cross-species transmission. In double infected animals persistent infections with both CAEV and MVV have been describe and viral chimeras generated by recombination between these variants have been detected. The present situation not only complicates animal trade between countries but favors the risk that high pathogenic variants may emerge as already observed in the past. Indeed in the early 1930’s a devastating outbreak of MVV in Iceland resulted in the death of over 100.000 sheep and the slaughtering of more than half million animals before the disease was eradicated. More recently, outbreaks with virulent strains were observed in Spain. SRLVs affecting wildlife have already been identified, demonstrating the existence of emergent viruses adapted to new hosts. Although controversial discussions that still persist about the direction of cross-species infection, SRLVs infecting sheep and goats follow a genomic evolution similar to that observed in HIV or in other lentiviruses. These divergent viral forms capable of crossing species barrier to cause productive infections outside small ruminants are an invaluable model system to investigate questions of host-tropism virus, evolution and lentiviral transmission. Viruses adapted to wildlife ruminants may acquire novel biopathological properties which may endanger not only the new host species but also domestic ruminants and humans. Lentivirus genetic diversity and host factors leading to establishment of naturally occurring virulent versus avirulent infections, and emergence of new strains challenge every aspect of SRLV control measures in order to provide efficient tools to prevent the transmission of diseases between wild ungulates and livestock. The description of phylogenetic analysis of SRLVs wildlife adapted and interspecies viral polymorphisms and characterization of their properties may lead to new approaches to disease prevention and strategies for an effective vaccine development.

Type of Paper: Review
Title: Impact of Small Ruminant Lentivirus for the understanding of primate lentivirus HIV and SIV
Author: Catherine Legras-Lachuer
Affiliation: Université Claude Bernard Lyon, France; Tel.: +33 (0)4 37 28 76 15, Fax +33 (0)6 63 43 24 04; E-Mail: catherine.lachuer@univ-lyon1.fr
Abstract: The Caprine arthritis-encephalitis virus (CAEV) and Maedi visna virus (MVV) are the small ruminant lentiviruses that infect goats and sheep. SRLV belongs to lentivirus genus such as the primate lentiviruses HIV and SIV. Like the other lentiviruses, they cause inflammatory disease provoking chronic lesions in several different organs but not immunodeficiency in their hosts. In an effort to understand the HIV and SIV infections and diseases, many studies have been carried on the SLRV and used these viruses as models. Here, we outline these studies including an overview of SLRV vectors, and models and discuss the current knowledge about SLRV infections.

Type of Paper: Review
Title: Small Ruminant Lentivirus: Variation Genetic, Tropism and Diagnostic
Authors: Hugo Ramírez ^1,*, Ramsés Reina ², Beatriz Amorena ², Damián de Andrés ³ and Humberto A. Martínez ¹
Affiliations: ¹ Laboratory of Virology, Genetics and Molecular Biology. FES-Cuautitlán, UNAM. C-4 Veterinary, Cuautitlán Izcalli, State of Mexico. Mexico. E-Mail: humberr55@gmail.com; ² Institute of Agrobiotechnology, CSIC-UPNA-Government of Navarra. Ctra. Mutilva Baja s/n, 31192, Navarra, Spain. ramses.reina@unavarra.es (R.R); bamorena@unavarra.es (B.A); ³ Chair of Hunting and Fishing Resources, University of Córdoba, Ctra Nacional IV-a Km 396, Córdoba 14071, Spain. E-Mail: ancad@unavarra.es; *  Author to whom correspondence should be addressed; E-Mail: ramiralh@unam.mx; Tel.: +52-55-56231920; Fax: +52-55-58705671.
Abstract: Small Ruminant Lentiviruses (SRLV) include Caprine Arthritis Encephalitis (CAEV) and Maedi Visna (MVV) or ovine progressive pneumonia (OPPV) viruses and cause a multisistemic chronic disease clinically characterized by progressive wasting (visna) and difficulty in breathing (maedi), encephalitis, arthritis and mastitis, affecting considerably the production and animal welfare. SRLV infections are present almost everywhere in the world with the exception of Iceland due to the stamping out policy carried out in the 70’s. The existence of a large genetic/antigenic variability in the SRLV has resulted in the identification of 5 genotypes (A - E) so far. Each genotype differs from the other in 25% to 37% of their nucleotide sequences. Among structural proteins, env is displayed on the surface of the virion, is responsible of binding to the host’s cell and therefore shows the most variable regions within the genome. Although reports describing new genetic SRLV sequences around the world are increasing, there is still little information on the viral genetic variability circulating in different geographic regions. In the current absence of vaccines and treatments, the success in controlling SRLV spread, depends not only on the early detection and elimination of infected animals in the flock but also on the use of appropriate diagnostic tests. However, the high genetic heterogeneity, variable antibody levels and low viral loads harden the interpretation of data obtained by currently available diagnostic techniques. SRLV have a marked in vivo tropism towards the monocyte / macrophage and dendritic cells lineage. Conserved amino acid sequences in specific positions of a viral protein have been described as signature patterns which can be related to the viral entry into the host’s cell and therefore in viral tropism. This is a brief overview of the current state of knowledge of the genetic variability, the tropism and its implications in the development of alternative diagnostic assays.

Type of Paper: Review
Title: Immunization against Small Ruminant Lentiviruses
Authors: Ramsés Reina, Damián de Andrés, Beatriz Amorena
Affiliation: Institute of Agrobiotechnology (CSIC-UPNA-Government of Navarra), Car. Mutilva 31192 Mutilva Baja (Navarra) Spain
Abstract: Small ruminant lentiviruses (SRLV) are distributed around the world causing a multisystemic disease in sheep and goats, which leads to production losses in detriment of animal welfare. In the absence of treatments, control is commonly based on serological diagnosis and culling of the seropositive animals and/or their progeny. However, detection of antibodies is largely affected by SRLV-intrinsic antigenic heterogeneity, limiting the efficiency of serological diagnosis.  
Novel strategies of immunization against SRLV have been explored as prophylactic measures in an effort to control SRLV spread and also to provide a useful model for HIV vaccines. These strategies involve inactivated whole virus, subunit vaccines, DNA encoding for viral proteins in the presence or absence of DNA encoding immunological adjuvants and live naturally or artificially attenuated viruses. In this review, we revisit comprehensively the immunization strategies, analyzing individually this double edged tool, as it may contribute to either control or enhance virus replication and disease.

Type of Paper: Review
Title: A Genetic Continuum of Lentiviral Species in Sheep and Goats
Authors: Leroux Caroline * and Mornex Jean-François
Affiliation: Joined Research Unit "Retrovirus and Comparative Pathology" UMR754 INRA Université Lyon 1, Team leader "Retrovirus, Evolution and Cancer", University Lyon 1, 50 Avenue Tony Garnier, 69007 Lyon, France; Tel. +33 4 37 28 76 20, Fax +33 4 37 28 76 05; E-Mail: caroline.leroux@univ-lyon1.fr
Abstract: Lentiviruses from distinct animal species have in common their genomic organization, the induction of slowly progressive diseases over months or years, the large spectrum of induced symptoms and concerned organs, the frequent inapparent infection without any detectable clinical signs and their ability to persist into their hosts. Based on limited number of complete sequences, lentiviruses infecting sheep and goats have been initially described as two distinct genetic groups evolving independently in sheep or goats. Since our original work in 1995, cumulative evidences from caprine and ovine field isolates clearly evidenced the circulation into the domestic small ruminant of a genetic continuum of SRLV (Small Ruminant Lentivirus) with viruses that did not simply clustered according to the animal species they were isolated from. This review will point out the need for a revision of their classification among the Lentivirus genus.

Type of Paper: Review
Title: Enhanced Management of Small Ruminant Lentiviruses Through Genetic Marker-Assisted Selective Breeding
Authors: Stephen N. White ^1,2 and Donald P. Knowles ^1,2
Affiliations: ¹ Animal Disease Research Unit, Agricultural Research Service, U.S. Department of Agriculture, Pullman, WA, USA; E-Mails: Stephen.White@ars.usda.gov (S.W.); Don.Knowles@ars.usda.gov (D.K.)
² Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA, USA; E-Mails: swhite@vetmed.wsu.edu (S.W.); dknowles@vetmed.wsu.edu (D.K.)
Abstract: Small ruminant lentiviruses include members that infect sheep (ovine lentivirus [OvLV]; also known as ovine progressive pneumonia virus/maedi-visna virus) and goats (caprine arthritis encephalitis virus [CAEV]).  Breed differences in seroprevalence and proviral concentration of OvLV had suggested a strong genetic component to susceptibility and control of OvLV infection in sheep.  A genetic marker test for susceptibility to OvLV has been developed recently based on the TMEM154 gene with validation data in many sheep flocks.  While no single genotype has been shown to have complete resistance to OvLV, consistent association in thousands of sheep from multiple breeds and management conditions highlight a new strategy for intervention by selective breeding.  This genetic marker-assisted selection (MAS) has the potential to be a useful addition to existing viral control measures.  Further, the discovery of multiple additional genomic regions associated with susceptibility to or control of OvLV suggests that additional genetic marker tests may be developed to extend the reach of MAS in the future.  This review will cover both the strengths and limitations of existing data from host genetics as an intervention and then outline additional questions for future research in both sheep and goats.

Title: Evolution of Specific Antibodies and Proviral DNA in Milk of Small Ruminants Infected by Small Ruminant Lentivirus
Authors: Nuria Barquero*, Esperanza Gomez-Lucia, Alvaro Arjona, Cristina Toural, Alfonso las Heras, José F. Fernández-Garayzabal, Ana Domenech
Affiliation: Dpto. Sanidad Animal. Facultad Veterinaria. Universidad Complutense. 28040 Madrid. Spain; (N.B) E-mail: nuria.barquero@vet.ucm.es
Abstract: The diagnosis of Small Ruminant Lentivirus (SRLV) is based on clinical signs, pathological lesions and laboratorial testing. However no "gold standard diagnostic test" has been developed up to the present. The aim of this study was to evaluate the presence of specific antibodies by ELISA and of SRLV proviral DNA by a PCR of the highly conserved pol region throughout time. A six-month study was conducted with the milk of 28 ewes and 31 goats intensively reared. The percentage of animals with antibodies against SRLV increased throughout the study period. Seroprevalence in sheep was 28% at the beginning of the study and by the end it had increased up to 52.4%. In goats, initial seroprevalence of 5.6% increased to 16%. The percentage of PCR positive ewes was stable throughout the study period but markedly decreased in June. Of the positive sheep, 21.43% were PCR-positive before antibodies could be detected. Contrarily, in 14.28% of the sheep, antibodies were detected prior to the proviral DNA. On the other hand, the PCR results in goats did not follow any pattern and oscillated between 35.29% and 55.6% depending on the month.

Title: Retroviral Infections in Sheep and Goats: Small Ruminant Lentiviruses and Host Interaction
Authors: Amaia Larruskain and Begoña M. Jugo
Affiliation: Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Science and Technology, University of the Basque Country UPV/EHU, Spain
Abstract: Small ruminant lentiviruses (SRLV) are members of the Retrovirus family comprising closely related Maedi-Visna Virus (MVV) and Caprine arthritis-encephalitis Virus (CAEV), which infect sheep and goats. Both retroviruses infect cells of the monocyte/macrophage lineage and cause lifelong infections.  Infection by MVV and CAEV can lead to Maedi-Visna (MV) and Caprine Arthritis-Encephalitis (CAE) respectively, chronic progressive inflammatory diseases primarily affecting the lungs, nervous system, joints and mammary glands. MV and CAE are distributed worldwide and develop over a period of months or years, always leading to the death of the host, with the consequent economic and welfare implications. Currently, the control of MV and CAE relies on the control of transmission and culling of infected animals. However, there is evidence that host genetics play an important role in determining Susceptibility/Resistance to SRLV infection and disease progression, but little work has been performed in small ruminants. More research is necessary to understand the host-SRLV interaction.