Biology and Pathogenesis of Lentiviruses

Narayan, Opendra; Clements, Janice E.

doi:10.1099/0022-1317-70-7-1617

Cited by 246 publications

(155 citation statements)

References 111 publications

(124 reference statements)

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“…The VISNA-infected sheep used here to map the CTL epitopes in POL had no clinical signs of VISNA infection during these experiments or at postmortem, suggesting they were controlling virus replication. It is in the late stages of VISNA disease that increased virus load and antigen are seen (Brodie et al, 1992;McNeilly et al, 2007;Narayan & Clements, 1989). With immunodeficiency viruses, control of virus load has been linked to the quality and strength of the antiviral CTL response (Heeney & Plotkin, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…interstitial pneumonitis, meningoencephalomyelitis, mastitis and arthritis (Narayan & Clements, 1989). VISNA is a member of the subfamily Lentivirinae, which includes human, simian, feline and bovine immunodeficiency viruses (HIV, SIV, FIV and BIV, respectively), equine infectious anaemia virus (EIAV) and the closely related caprine arthritis encephalitis virus (CAEV).…”

Section: Introductionmentioning

confidence: 99%

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Mapping and characterization of visna/maedi virus cytotoxic T-lymphocyte epitopes

Barbezange

McConnell

et al. 2008

Journal of General Virology

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CD8 + cytotoxic T-lymphocyte (CTL) responses have been shown to be important in the control of human and simian immunodeficiency virus infections. Infection of sheep with visna/maedi virus (VISNA), a related lentivirus, induces specific CD8 + CTL in vivo, but the specific viral proteins recognized are not known. To determine which VISNA antigens were recognized by sheep CTL, we used recombinant vaccinia viruses expressing the different genes of VISNA: in six sheep (Finnish Landrace¾Dorset crosses, Friesland and Lleyn breeds) all VISNA proteins were recognized except TAT. Two sheep, shown to share major histocompatibility complex (MHC) class I alleles, recognized POL and were used to map the epitope. The pol gene is 3267 bp long encoding 1088 aa. By using recombinant vaccinia viruses a central portion (nt 1609-2176, aa 537-725) was found to contain the CTL epitope and this was mapped with synthetic peptides to a 25 aa region (aa 612-636). When smaller peptides were used, a cluster of epitopes was detected: at least three epitopes were present, at positions 612-623: DSRYAFEFMIRN; 620-631: MIRNWDEEVIKN; and 625-635: EEVIKNPIQAR. A DNA-prime-modified vaccinia virus Ankara (MVA)-boost strategy was employed to immunize four sheep shown to share MHC class I allele(s) with the sheep above. Specific CTL activity developed in all the immunized sheep within 3 weeks of the final MVA boost although half the sheep showed evidence of specific reactivity after the DNA-prime immunizations. This is the first report, to our knowledge, of induction of CTL by a DNA-prime-boost method in VISNA infection. INTRODUCTIONVisna/maedi virus (VISNA) establishes a life-long infection of sheep, leading to progressive inflammatory disease in multiple organs, e.g. interstitial pneumonitis, meningoencephalomyelitis, mastitis and arthritis (Narayan & Clements, 1989). VISNA is a member of the subfamily Lentivirinae, which includes human, simian, feline and bovine immunodeficiency viruses (HIV, SIV, FIV and BIV, respectively), equine infectious anaemia virus (EIAV) and the closely related caprine arthritis encephalitis virus (CAEV). Unlike HIV and other immunodeficiency viruses, VISNA infects cells of the monocyte/macrophage lineage and dendritic cells but not T lymphocytes (Gendelman et al., 1985(Gendelman et al., , 1986Gorrell et al., 1992;Ryan et al., 2000). Due to the tropism for mononuclear phagocytes, lymphoid tissues are considered to be important targets for the replication of VISNA (Blacklaws et al., 1995a; Pétursson et al., 1991). This restriction in tropism makes VISNA a unique model for understanding immunity to and pathogenesis of lentiviruses in the absence of T-cell infection in the infected host.Cytotoxic T-lymphocytes (CTL) play an important role in immune control of both acute and chronic viral infections and are key immunological mediators of viral clearance (Harty et al., 2000;Wong & Pamer, 2003). In lentiviral infections, control of replication of HIV and SIV has been linked strongly to robust specific CD8 + CTL although CD4 +...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mapping and characterization of visna/maedi virus cytotoxic T-lymphocyte epitopes

Barbezange

McConnell

et al. 2008

Journal of General Virology

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“…Since then, several other members of this genus of the family Retroviridae have been identified, including caprine arthritis encephalitis virus (CAEV), equine infectious anemia virus (EIAV) and human, simian, feline and bovine immunodeficiency viruses (HIV, SIV, FIV and BIV respectively). VMV has long been considered the prototype lentivirus ( Carey andDalziel, 1993 andClements, 1989) and has been widely employed to study many aspects of lentiviral infections, such as the molecular mechanisms underlying viral tropism ( Agnarsdóttir et al, 2000, Barros et al, 2005, Chebloune et al, 1996and Óskarsson et al, 2007, persistence and pathogenesis ( Torsteinsdottir et al, 2007), routes of viral transmission ( Blacklaws et al, 2004) and strategies to eradicate or prevent the infection ). The British VMV strain EV1 was isolated from a sheep displaying symptoms of arthritis and pneumonia and its complete genome was cloned and sequenced ( Sargan et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

Development and comparison of strain specific gag and pol real-time PCR assays for the detection of Visna/maedi virus

Carrozza

Mazzei

Bandecchi

et al. 2010

Journal of Virological Methods

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The aim of this study was the development of gag and pol dual labelled probe real-time PCR and RT PCR assays to quantify the proviral load and the transcripts of the British Visna/maedi virus EV1 strain. Primers and probes were chosen based on the consensus sequences of gag and pol clones representative of EV1 genetic variants. Both PCRs had a detection limit of 3 copies of target gene, with a linearity over 6 orders of magnitude. The performances of the two PCRs in vivo were evaluated and compared on a panel of DNAs extracted from blood of sheep infected experimentally with EV1. The pol assay detected in most cases lower numbers of viral molecules than gag assay, yielding some false negative results. The gag real-time RT PCR had a detection limit of 100 RNA molecules with a linearity over 5 orders of magnitude. This did not result in a lower performance of the RT PCR compared to the PCR in cells permissive for virus replication, which contain higher numbers of viral transcripts than proviral genomes. The real-time assays developed in this study, particularly the gag assay, provide a sensitive tool which can be used to quantify the viral load in experimental infections

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“…It causes pneumonia (Maedi), encephalitis (Visna), arthritis and/or mastitis in sheep (Van derMolen and Houwers 1987;Houwers et al 1988;Narayan and Clements 1989). The infection is mainly transmitted by the respiratory route and by colostrum.…”

mentioning

confidence: 99%

Detection of Visna Maedi virus in mesenteric lymph nodes and in other lymphoid tissues of sheep three years after respiratory infection

Preziuso¹,

Magi²,

Mari³

et al. 2013

Vet. Med. - Czech

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Visna/Maedi virus (VMV), a small ruminant lentivirus responsible for lymphoproliferative pneumonia, encephalitis, arthritis and/or mastitis in sheep, has been detected in different non-lymphoid organs. However, only a few investigations have been carried out in lymphoid tissues. In this study, some lymphoid tissues and lymph node draining or non-draining VMV target organs from five sheep infected experimentally by the respiratory route three years previously were investigated. Archival samples of spleen, red bone marrow, caudal mediastinal lymph nodes, mammary lymph nodes, popliteal lymph nodes and mesenteric lymph nodes were tested by PCR for the presence of proviral DNA. Popliteal and mesenteric lymph node samples were tested also by immunohistochemical staining of the viral capsid antigen p28. The proviral DNA was detected by PCR in all the lymphoid tissue samples from the infected sheep. The viral antigen was stained in mononuclear cells in popliteal and mesenteric lymph nodes of the infected sheep. Although the lymph nodes draining the classical target organs seem to be more infected than the others, both the viral capsid antigen and the proviral DNA were present also in lymph nodes draining non-target organs, such as the mesenteric lymph nodes. These findings show the presence of VMV in different lymphoid tissues in the late stages of infection and suggest a potential role of these tissues as a site for viral reservoir and replication, even three years after infection.

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Biology and Pathogenesis of Lentiviruses

Cited by 246 publications

References 111 publications

Mapping and characterization of visna/maedi virus cytotoxic T-lymphocyte epitopes

Mapping and characterization of visna/maedi virus cytotoxic T-lymphocyte epitopes

Development and comparison of strain specific gag and pol real-time PCR assays for the detection of Visna/maedi virus

Detection of Visna Maedi virus in mesenteric lymph nodes and in other lymphoid tissues of sheep three years after respiratory infection

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