FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / J Virol / The S2 gene of equine infectious anemia virus is a highly co...
Journal of virology1999; 74(1); 573-579; doi: 10.1128/jvi.74.1.573-579.2000

The S2 gene of equine infectious anemia virus is a highly conserved determinant of viral replication and virulence properties in experimentally infected ponies.

Abstract: Equine infectious anemia virus (EIAV) is genetically one of the simplest lentiviruses in that the viral genome encodes only three accessory genes, tat, rev, and S2. Although serological analyses demonstrate the expression of the S2 protein in persistently infected horses, the role of this viral gene remains undefined. We recently reported that the S2 gene is not essential for EIAV replication in primary equine macrophages, as EIAV mutants lacking the S2 gene replicate to levels similar to those of the parental virus (F. Li, B. A. Puffer, and R. C. Montelaro, J. Virol. 72:8344-8348, 1998). We now describe in vivo studies that examine the evolution and role of the S2 gene in ponies experimentally infected with EIAV. The results of these studies reveal for the first time that the S2 gene is highly conserved during persistent infection and that deletion of the S2 gene reduces viral virulence and virus replication levels compared to those of the parental virus containing a functional S2 gene. These data indicate that the EIAV S2 gene is in fact an important determinant of viral replication and pathogenic properties in vivo, despite the evident lack of S2 influence on viral replication levels in vitro. Thus, these observations suggest in vivo functions of EIAV S2 that are not adequately reflected in simple infections of cultured cells, including natural target macrophages.
Get Full Text
Publication Date: 1999-12-10 PubMed ID: 10590152PubMed Central: PMC111574DOI: 10.1128/jvi.74.1.573-579.2000Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Research Support
  • Non-U.S. Gov't
  • Research Support
  • U.S. Gov't
  • P.H.S.

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article discusses how the S2 gene in equine infectious anemia virus (EIAV) significantly contributes to the virus’s replication and virulence properties in horses, despite in vitro studies suggesting otherwise.

Background of the Research

  • EIAV, a type of lentivirus, has a remarkably simple genetic structure, encoding only three accessory genes: tat, rev, and S2.
  • Even though the S2 protein is found in horses persistently infected with EIAV, the function of the S2 gene is unknown.
  • A previous study by the same researchers reported that the S2 gene is not necessary for EIAV replication in primary equine macrophages. This conclusion was based on observing EIAV mutants without the S2 gene replicating to similar levels as the original virus (in vitro).

Objective and Methodology of the Study

  • The objective of the current study was to examine the role and evolution of the S2 gene in ponies that were experimentally infected with EIAV (in vivo).
  • The researchers examined the behavior of the virus in the infected ponies, comparing the virus’s behavior when the S2 gene was present versus when it was deleted.

Key Findings of the Study

  • The results found that the S2 gene was highly conserved throughout persistent infection, suggesting a significant function within the viral lifespan.
  • When the S2 gene was deleted from the virus, its virulence and replication levels decreased compared to the parent virus with a functional S2 gene.

Conclusions Drawn from the Research

  • This empirical study demonstrated that the EIAV S2 gene is an important determinant of viral replication and traits that contribute to disease in live subjects (in vivo).
  • However, these in vivo functions of the EIAV S2 gene are not adequately reflected in controlled lab studies (in vitro), specifically in simple infections of naturally targeted macrophages. This highlights the importance of performing studies in more complex living systems when studying viral pathogenesis.

Cite This Article

APA
Li F, Leroux C, Craigo JK, Cook SJ, Issel CJ, Montelaro RC. (1999). The S2 gene of equine infectious anemia virus is a highly conserved determinant of viral replication and virulence properties in experimentally infected ponies. J Virol, 74(1), 573-579. https://doi.org/10.1128/jvi.74.1.573-579.2000

Publication

Journal of virology
ISSN: 0022-538X
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 74
Issue: 1
Pages: 573-579

Researcher Affiliations

Li, F
  • Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
Leroux, C
    Craigo, J K
      Cook, S J
        Issel, C J
          Montelaro, R C

            MeSH Terms

            • Amino Acid Sequence
            • Amino Acid Substitution
            • Animals
            • Cells, Cultured
            • Conserved Sequence
            • Genes, Viral
            • Horses
            • Infectious Anemia Virus, Equine / genetics
            • Infectious Anemia Virus, Equine / pathogenicity
            • Infectious Anemia Virus, Equine / physiology
            • Molecular Sequence Data
            • Sequence Homology, Amino Acid
            • Viral Proteins / chemistry
            • Viral Proteins / genetics
            • Virulence / genetics
            • Virus Replication / genetics

            Grant Funding

            • R01 CA049296 / NCI NIH HHS
            • R01CA49296 / NCI NIH HHS

            References

            This article includes 22 references
            1. Cook RF, Leroux C, Cook SJ, Berger SL, Lichtenstein DL, Ghabrial NN, Montelaro RC, Issel CJ. Development and characterization of an in vivo pathogenic molecular clone of equine infectious anemia virus.. J Virol 1998 Feb;72(2):1383-93.
              pmc: PMC124617pubmed: 9445039doi: 10.1128/jvi.72.2.1383-1393.1998google scholar: lookup
            2. Cullen BR. HIV-1 auxiliary proteins: making connections in a dying cell.. Cell 1998 May 29;93(5):685-92.
              pubmed: 9630214doi: 10.1016/s0092-8674(00)81431-2google scholar: lookup
            3. Ten Haaft P, Verstrepen B, Uberla K, Rosenwirth B, Heeney J. A pathogenic threshold of virus load defined in simian immunodeficiency virus- or simian-human immunodeficiency virus-infected macaques.. J Virol 1998 Dec;72(12):10281-5.
              pmc: PMC110614pubmed: 9811776doi: 10.1128/jvi.72.12.10281-10285.1998google scholar: lookup
            4. Hirsch VM, Sharkey ME, Brown CR, Brichacek B, Goldstein S, Wakefield J, Byrum R, Elkins WR, Hahn BH, Lifson JD, Stevenson M. Vpx is required for dissemination and pathogenesis of SIV(SM) PBj: evidence of macrophage-dependent viral amplification.. Nat Med 1998 Dec;4(12):1401-8.
              pubmed: 9846578doi: 10.1038/3992google scholar: lookup
            5. Kawakami T, Sherman L, Dahlberg J, Gazit A, Yaniv A, Tronick SR, Aaronson SA. Nucleotide sequence analysis of equine infectious anemia virus proviral DNA.. Virology 1987 Jun;158(2):300-12.
              pubmed: 3035786doi: 10.1016/0042-6822(87)90202-9google scholar: lookup
            6. Kestler HW 3rd, Ringler DJ, Mori K, Panicali DL, Sehgal PK, Daniel MD, Desrosiers RC. Importance of the nef gene for maintenance of high virus loads and for development of AIDS.. Cell 1991 May 17;65(4):651-62.
              pubmed: 2032289doi: 10.1016/0092-8674(91)90097-igoogle scholar: lookup
            7. Lang SM, Weeger M, Stahl-Hennig C, Coulibaly C, Hunsmann G, Müller J, Müller-Hermelink H, Fuchs D, Wachter H, Daniel MM. Importance of vpr for infection of rhesus monkeys with simian immunodeficiency virus.. J Virol 1993 Feb;67(2):902-12.
              pmc: PMC237444pubmed: 8380472doi: 10.1128/jvi.67.2.902-912.1993google scholar: lookup
            8. Leroux C, Issel CJ, Montelaro RC. Novel and dynamic evolution of equine infectious anemia virus genomic quasispecies associated with sequential disease cycles in an experimentally infected pony.. J Virol 1997 Dec;71(12):9627-39.
              pmc: PMC230271pubmed: 9371627doi: 10.1128/jvi.71.12.9627-9639.1997google scholar: lookup
            9. Li F, Puffer BA, Montelaro RC. The S2 gene of equine infectious anemia virus is dispensable for viral replication in vitro.. J Virol 1998 Oct;72(10):8344-8.
              pmc: PMC110207pubmed: 9733881doi: 10.1128/jvi.72.10.8344-8348.1998google scholar: lookup
            10. Lichtenstein DL, Rushlow KE, Cook RF, Raabe ML, Swardson CJ, Kociba GJ, Issel CJ, Montelaro RC. Replication in vitro and in vivo of an equine infectious anemia virus mutant deficient in dUTPase activity.. J Virol 1995 May;69(5):2881-8.
              pmc: PMC188985pubmed: 7707512doi: 10.1128/jvi.69.5.2881-2888.1995google scholar: lookup
            11. Lifson JD, Nowak MA, Goldstein S, Rossio JL, Kinter A, Vasquez G, Wiltrout TA, Brown C, Schneider D, Wahl L, Lloyd AL, Williams J, Elkins WR, Fauci AS, Hirsch VM. The extent of early viral replication is a critical determinant of the natural history of simian immunodeficiency virus infection.. J Virol 1997 Dec;71(12):9508-14.
              pmc: PMC230257pubmed: 9371613doi: 10.1128/jvi.71.12.9508-9514.1997google scholar: lookup
            12. Maury W. Monocyte maturation controls expression of equine infectious anemia virus.. J Virol 1994 Oct;68(10):6270-9.
              pmc: PMC237047pubmed: 8083967doi: 10.1128/jvi.68.10.6270-6279.1994google scholar: lookup
            13. McGuire TC, Lacy PA, O'Rourke KI. cDNA sequence of the env gene of a pathogenic equine infectious anemia lentivirus variant.. Nucleic Acids Res 1990 Jan 11;18(1):196.
              pmc: PMC330234pubmed: 2155398doi: 10.1093/nar/18.1.196google scholar: lookup
            14. Mellors JW, Rinaldo CR Jr, Gupta P, White RM, Todd JA, Kingsley LA. Prognosis in HIV-1 infection predicted by the quantity of virus in plasma.. Science 1996 May 24;272(5265):1167-70.
              pubmed: 8638160doi: 10.1126/science.272.5265.1167google scholar: lookup
            15. Miller K, Storts D R. An improved single buffer, two enzyme system for RT-PCR. J NIH Res 1996;8:48.
            16. Montelaro R C, Ball J M, Rushlow K E. Equine retroviruses. In: Levy J A, editor. The Retroviridae. Vol. 2. New York, N.Y: Plenum Press; 1993. pp. 257–360.
            17. Raabe ML, Issel CJ, Cook SJ, Cook RF, Woodson B, Montelaro RC. Immunization with a recombinant envelope protein (rgp90) of EIAV produces a spectrum of vaccine efficacy ranging from lack of clinical disease to severe enhancement.. Virology 1998 May 25;245(1):151-62.
              pubmed: 9614876doi: 10.1006/viro.1998.9142google scholar: lookup
            18. Raabe MR, Issel CJ, Montelaro RC. Equine monocyte-derived macrophage cultures and their applications for infectivity and neutralization studies of equine infectious anemia virus.. J Virol Methods 1998 Mar;71(1):87-104.
              pubmed: 9628225doi: 10.1016/s0166-0934(97)00204-8google scholar: lookup
            19. Rushlow K, Olsen K, Stiegler G, Payne SL, Montelaro RC, Issel CJ. Lentivirus genomic organization: the complete nucleotide sequence of the env gene region of equine infectious anemia virus.. Virology 1986 Dec;155(2):309-21.
              pubmed: 2431539doi: 10.1016/0042-6822(86)90195-9google scholar: lookup
            20. Schiltz RL, Shih DS, Rasty S, Montelaro RC, Rushlow KE. Equine infectious anemia virus gene expression: characterization of the RNA splicing pattern and the protein products encoded by open reading frames S1 and S2.. J Virol 1992 Jun;66(6):3455-65.
              pmc: PMC241126pubmed: 1316461doi: 10.1128/jvi.66.6.3455-3465.1992google scholar: lookup
            21. Sellon DC, Walker KM, Russell KE, Perry ST, Covington P, Fuller FJ. Equine infectious anemia virus replication is upregulated during differentiation of blood monocytes from acutely infected horses.. J Virol 1996 Jan;70(1):590-4.
              pmc: PMC189850pubmed: 8523576doi: 10.1128/jvi.70.1.590-594.1996google scholar: lookup
            22. Trono D. HIV accessory proteins: leading roles for the supporting cast.. Cell 1995 Jul 28;82(2):189-92.
              pubmed: 7628010doi: 10.1016/0092-8674(95)90306-2google scholar: lookup

            Citations

            This article has been cited 19 times.
            1. Munis AM. Gene Therapy Applications of Non-Human Lentiviral Vectors.. Viruses 2020 Sep 29;12(10).
              doi: 10.3390/v12101106pubmed: 33003635google scholar: lookup
            2. Ahmad I, Li S, Li R, Chai Q, Zhang L, Wang B, Yu C, Zheng YH. The retroviral accessory proteins S2, Nef, and glycoMA use similar mechanisms for antagonizing the host restriction factor SERINC5.. J Biol Chem 2019 Apr 26;294(17):7013-7024.
              doi: 10.1074/jbc.RA119.007662pubmed: 30862674google scholar: lookup
            3. Gonzalez-Enriquez GV, Escoto-Delgadillo M, Vazquez-Valls E, Torres-Mendoza BM. SERINC as a Restriction Factor to Inhibit Viral Infectivity and the Interaction with HIV.. J Immunol Res 2017;2017:1548905.
              doi: 10.1155/2017/1548905pubmed: 29359168google scholar: lookup
            4. Chande A, Cuccurullo EC, Rosa A, Ziglio S, Carpenter S, Pizzato M. S2 from equine infectious anemia virus is an infectivity factor which counteracts the retroviral inhibitors SERINC5 and SERINC3.. Proc Natl Acad Sci U S A 2016 Nov 15;113(46):13197-13202.
              doi: 10.1073/pnas.1612044113pubmed: 27803322google scholar: lookup
            5. Wang XF, Wang S, Liu Q, Lin YZ, Du C, Tang YD, Na L, Wang X, Zhou JH. A unique evolution of the s2 gene of equine infectious anemia virus in hosts correlated with particular infection statuses.. Viruses 2014 Nov 10;6(11):4265-79.
              doi: 10.3390/v6114265pubmed: 25390683google scholar: lookup
            6. Yin X, Hu Z, Gu Q, Wu X, Zheng YH, Wei P, Wang X. Equine tetherin blocks retrovirus release and its activity is antagonized by equine infectious anemia virus envelope protein.. J Virol 2014 Jan;88(2):1259-70.
              doi: 10.1128/JVI.03148-13pubmed: 24227834google scholar: lookup
            7. Craigo JK, Ezzelarab C, Cook SJ, Chong L, Horohov D, Issel CJ, Montelaro RC. Envelope determinants of equine lentiviral vaccine protection.. PLoS One 2013;8(6):e66093.
              doi: 10.1371/journal.pone.0066093pubmed: 23785473google scholar: lookup
            8. Farley DC, Bannister R, Leroux-Carlucci MA, Evans NE, Miskin JE, Mitrophanous KA. Development of an equine-tropic replication-competent lentivirus assay for equine infectious anemia virus-based lentiviral vectors.. Hum Gene Ther Methods 2012 Oct;23(5):309-23.
              doi: 10.1089/hgtb.2012.102pubmed: 23121195google scholar: lookup
            9. Craigo JK, Ezzelarab C, Montelaro RC. Development of a high throughput, semi-automated, infectious center cell-based ELISA for equine infectious anemia virus.. J Virol Methods 2012 Nov;185(2):221-7.
              doi: 10.1016/j.jviromet.2012.07.007pubmed: 22820072google scholar: lookup
            10. Craigo JK, Barnes S, Cook SJ, Issel CJ, Montelaro RC. Divergence, not diversity of an attenuated equine lentivirus vaccine strain correlates with protection from disease.. Vaccine 2010 Nov 29;28(51):8095-104.
              doi: 10.1016/j.vaccine.2010.10.003pubmed: 20955830google scholar: lookup
            11. Qi X, Wang X, Wang S, Lin Y, Jiang C, Ma J, Zhao L, Lv X, Shen R, Wang F, Kong X, Su Z, Zhou J. Genomic analysis of an effective lentiviral vaccine-attenuated equine infectious anemia virus vaccine EIAV FDDV13.. Virus Genes 2010 Aug;41(1):86-98.
              doi: 10.1007/s11262-010-0491-6pubmed: 20526660google scholar: lookup
            12. Covaleda L, Gno BT, Fuller FJ, Payne SL. Identification of cellular proteins interacting with equine infectious anemia virus S2 protein.. Virus Res 2010 Aug;151(2):235-9.
              doi: 10.1016/j.virusres.2010.04.007pubmed: 20417672google scholar: lookup
            13. Covaleda L, Fuller FJ, Payne SL. EIAV S2 enhances pro-inflammatory cytokine and chemokine response in infected macrophages.. Virology 2010 Feb 5;397(1):217-23.
              doi: 10.1016/j.virol.2009.11.005pubmed: 19945727google scholar: lookup
            14. Zielonka J, Bravo IG, Marino D, Conrad E, Perković M, Battenberg M, Cichutek K, Münk C. Restriction of equine infectious anemia virus by equine APOBEC3 cytidine deaminases.. J Virol 2009 Aug;83(15):7547-59.
              doi: 10.1128/JVI.00015-09pubmed: 19458006google scholar: lookup
            15. Craigo JK, Li F, Steckbeck JD, Durkin S, Howe L, Cook SJ, Issel C, Montelaro RC. Discerning an effective balance between equine infectious anemia virus attenuation and vaccine efficacy.. J Virol 2005 Mar;79(5):2666-77.
              doi: 10.1128/JVI.79.5.2666-2677.2005pubmed: 15708986google scholar: lookup
            16. Jin S, Issel CJ, Montelaro RC. Serological method using recombinant S2 protein to differentiate equine infectious anemia virus (EIAV)-infected and EIAV-vaccinated horses.. Clin Diagn Lab Immunol 2004 Nov;11(6):1120-9.
              doi: 10.1128/CDLI.11.6.1120-1129.2004pubmed: 15539516google scholar: lookup
            17. Li F, Craigo JK, Howe L, Steckbeck JD, Cook S, Issel C, Montelaro RC. A live attenuated equine infectious anemia virus proviral vaccine with a modified S2 gene provides protection from detectable infection by intravenous virulent virus challenge of experimentally inoculated horses.. J Virol 2003 Jul;77(13):7244-53.
              doi: 10.1128/jvi.77.13.7244-7253.2003pubmed: 12805423google scholar: lookup
            18. Maury W, Wright PJ, Bradley S. Characterization of a cytolytic strain of equine infectious anemia virus.. J Virol 2003 Feb;77(4):2385-99.
              doi: 10.1128/jvi.77.4.2385-2399.2003pubmed: 12551976google scholar: lookup
            19. Hammond SA, Li F, McKeon BM Sr, Cook SJ, Issel CJ, Montelaro RC. Immune responses and viral replication in long-term inapparent carrier ponies inoculated with equine infectious anemia virus.. J Virol 2000 Jul;74(13):5968-81.
              doi: 10.1128/jvi.74.13.5968-5981.2000pubmed: 10846078google scholar: lookup
            Subscribe to our newsletter
            Join 99,344 horse owners like you who receive our email updates on horse health and nutrition.