1887

Abstract

We have shown previously that a type-specific neutralization domain is located within a 39 aa sequence in the fourth variable domain of gp135 in visna/maedi virus. We now show that neutralizing antibodies detected early in infection are directed to this epitope, suggesting an immunodominant nature of this domain. Ten antigenic variants were previously analysed for mutations in this region, and all but one were found to be mutated. To assess the importance of these mutations in replication and neutralization, we reconstructed several of the mutations in an infectious molecular clone and tested the resulting viruses for neutralization phenotype and replication. Mutation of a conserved cysteine was shown to alter the neutralization epitope, whilst the replication kinetics in macrophages were unchanged. Mutations modulating potential glycosylation sites were found in seven of the ten antigenic variants. A frequently occurring mutation, removing a potential glycosylation site, had no effect on its own on the neutralization phenotype of the virus. However, adding an extra potential glycosylation site in the region resulted in antigenic escape. The results indicate that the conserved cysteine plays a role in the structure of the epitope and that glycosylation may shield the principal neutralization site.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.83410-0
2008-03-01
2020-01-23
Loading full text...

Full text loading...

/deliver/fulltext/jgv/89/3/716.html?itemId=/content/journal/jgv/10.1099/vir.0.83410-0&mimeType=html&fmt=ahah

References

  1. Andresdottir, V., Tang, X., Agnarsdottir, G., Andresson, O. S., Georgsson, G., Skraban, R., Torsteinsdottir, S., Rafnar, B., Benediktsdottir, E. & other authors ( 1998; ). Biological and genetic differences between lung- and brain-derived isolates of maedi-visna virus. Virus Genes 16, 281–293.[CrossRef]
    [Google Scholar]
  2. Andresdottir, V., Skraban, R., Matthiasdottir, S., Lutley, R., Agnarsdottir, G. & Thorsteinsdottir, H. ( 2002; ). Selection of antigenic variants in maedi-visna virus infection. J Gen Virol 83, 2543–2551.
    [Google Scholar]
  3. Andresson, O. S., Elser, J. E., Tobin, G. J., Greenwood, J. D., Gonda, M. A., Georgsson, G., Andresdottir, V., Benediktsdottir, E., Carlsdottir, H. M. & other authors ( 1993; ). Nucleotide sequence and biological properties of a pathogenic proviral molecular clone of neurovirulent visna virus. Virology 193, 89–105.[CrossRef]
    [Google Scholar]
  4. Back, N. K., Smit, L., De Jong, J. J., Keulen, W., Schutten, M., Goudsmit, J. & Tersmette, M. ( 1994; ). An N-glycan within the human immunodeficiency virus type 1 gp120 V3 loop affects virus neutralization. Virology 199, 431–438.[CrossRef]
    [Google Scholar]
  5. Cheevers, W. P., Knowles, D. P., Jr & Norton, L. K. ( 1991; ). Neutralization-resistant antigenic variants of caprine arthritis-encephalitis lentivirus associated with progressive arthritis. J Infect Dis 164, 679–685.[CrossRef]
    [Google Scholar]
  6. Cheevers, W. P., McGuire, T. C., Norton, L. K., Cordery-Cotter, R. & Knowles, D. P. ( 1993; ). Failure of neutralizing antibody to regulate CAE lentivirus expression in vivo. Virology 196, 835–839.[CrossRef]
    [Google Scholar]
  7. Cheng-Mayer, C., Brown, A., Harouse, J., Luciw, P. A. & Mayer, A. J. ( 1999; ). Selection for neutralization resistance of the simian/human immunodeficiency virus SHIVSF33A variant in vivo by virtue of sequence changes in the extracellular envelope glycoprotein that modify N-linked glycosylation. J Virol 73, 5294–5300.
    [Google Scholar]
  8. Frost, S. D., Wrin, T., Smith, D. M., Kosakovsky Pond, S. L., Liu, Y., Paxinos, E., Chappey, C., Galovich, J., Beauchaine, J. & other authors ( 2005; ). Neutralizing antibody responses drive the evolution of human immunodeficiency virus type 1 envelope during recent HIV infection. Proc Natl Acad Sci U S A 102, 18514–18519.[CrossRef]
    [Google Scholar]
  9. Gallaher, W. R., Ball, J. M., Garry, R. F., Martin-Amedee, A. M. & Montelaro, R. C. ( 1995; ). A general model for the surface glycoproteins of HIV and other retroviruses. AIDS Res Hum Retroviruses 11, 191–202.[CrossRef]
    [Google Scholar]
  10. Gjerset, B., Jonassen, C. M. & Rimstad, E. ( 2007; ). Natural transmission and comparative analysis of small ruminant lentiviruses in the Norwegian sheep and goat populations. Virus Res 125, 153–161.[CrossRef]
    [Google Scholar]
  11. Gorrell, M. D., Brandon, M. R., Sheffer, D., Adams, R. J. & Narayan, O. ( 1992; ). Ovine lentivirus is macrophagetropic and does not replicate productively in T lymphocytes. J Virol 66, 2679–2688.
    [Google Scholar]
  12. Gudnadottir, M. ( 1974; ). Visna-maedi in sheep. Prog Med Virol 18, 336–349.
    [Google Scholar]
  13. Hartley, O., Klasse, P. J., Sattentau, Q. J. & Moore, J. P. ( 2005; ). V3: HIV's switch-hitter. AIDS Res Hum Retroviruses 21, 171–189.[CrossRef]
    [Google Scholar]
  14. Hotzel, I. & Cheevers, W. P. ( 2001; ). Conservation of human immunodeficiency virus type 1 gp120 inner-domain sequences in lentivirus and type A and B retrovirus envelope surface glycoproteins. J Virol 75, 2014–2018.[CrossRef]
    [Google Scholar]
  15. Hotzel, I. & Cheevers, W. P. ( 2003; ). Caprine arthritis-encephalitis virus envelope surface glycoprotein regions interacting with the transmembrane glycoprotein: structural and functional parallels with human immunodeficiency virus type 1 gp120. J Virol 77, 11578–11587.[CrossRef]
    [Google Scholar]
  16. Hotzel, I. & Cheevers, W. P. ( 2005; ). Mutations increasing exposure of a receptor binding site epitope in the soluble and oligomeric forms of the caprine arthritis-encephalitis lentivirus envelope glycoprotein. Virology 339, 261–272.[CrossRef]
    [Google Scholar]
  17. Huang, C. C., Tang, M., Zhang, M. Y., Majeed, S., Montabana, E., Stanfield, R. L., Dimitrov, D. S., Korber, B., Sodroski, J. & other authors ( 2005; ). Structure of a V3-containing HIV-1 gp120 core. Science 310, 1025–1028.[CrossRef]
    [Google Scholar]
  18. Huso, D. L., Narayan, O. & Hart, G. W. ( 1988; ). Sialic acids on the surface of caprine arthritis-encephalitis virus define the biological properties of the virus. J Virol 62, 1974–1980.
    [Google Scholar]
  19. Javaherian, K., Langlois, A. J., McDanal, C., Ross, K. L., Eckler, L. I., Jellis, C. L., Profy, A. T., Rusche, J. R., Bolognesi, D. P. & other authors ( 1989; ). Principal neutralizing domain of the human immunodeficiency virus type 1 envelope protein. Proc Natl Acad Sci U S A 86, 6768–6772.[CrossRef]
    [Google Scholar]
  20. Kinsey, N. E., Anderson, M. G., Unangst, T. J., Joag, S. V., Narayan, O., Zink, M. C. & Clements, J. E. ( 1996; ). Antigenic variation of SIV: mutations in V4 alter the neutralization profile. Virology 221, 14–21.[CrossRef]
    [Google Scholar]
  21. Kwong, P. D., Doyle, M. L., Casper, D. J., Cicala, C., Leavitt, S. A., Majeed, S., Steenbeke, T. D., Venturi, M., Chaiken, I. & other authors ( 2002; ). HIV-1 evades antibody-mediated neutralization through conformational masking of receptor-binding sites. Nature 420, 678–682.[CrossRef]
    [Google Scholar]
  22. Li, Y., Luo, L., Rasool, N. & Kang, C. Y. ( 1993; ). Glycosylation is necessary for the correct folding of human immunodeficiency virus gp120 in CD4 binding. J Virol 67, 584–588.
    [Google Scholar]
  23. Lutley, R., Petursson, G., Palsson, P. A., Georgsson, G., Klein, J. & Nathanson, N. ( 1983; ). Antigenic drift in visna: virus variation during long-term infection of Icelandic sheep. J Gen Virol 64, 1433–1440.[CrossRef]
    [Google Scholar]
  24. Moog, C., Fleury, H. J., Pellegrin, I., Kirn, A. & Aubertin, A. M. ( 1997; ). Autologous and heterologous neutralizing antibody responses following initial seroconversion in human immunodeficiency virus type 1-infected individuals. J Virol 71, 3734–3741.
    [Google Scholar]
  25. Mwaengo, D. M., Grant, R. F., DeMartini, J. C. & Carlson, J. O. ( 1997; ). Envelope glycoprotein nucleotide sequence and genetic characterization of North American ovine lentiviruses. Virology 238, 135–144.[CrossRef]
    [Google Scholar]
  26. Nara, P. L., Smit, L., Dunlop, N., Hatch, W., Merges, M., Waters, D., Kelliher, J., Gallo, R. C., Fischinger, P. J. & Goudsmit, J. ( 1990; ). Emergence of viruses resistant to neutralization by V3-specific antibodies in experimental human immunodeficiency virus type 1 IIIB infection of chimpanzees. J Virol 64, 3779–3791.
    [Google Scholar]
  27. Narayan, O., Griffin, D. E. & Chase, J. ( 1977; ). Antigenic shift of visna virus in persistently infected sheep. Science 197, 376–378.[CrossRef]
    [Google Scholar]
  28. Narayan, O., Griffin, D. E. & Clements, J. E. ( 1978; ). Virus mutation during ‘slow infection’: temporal development and characterization of mutants of visna virus recovered from sheep. J Gen Virol 41, 343–352.[CrossRef]
    [Google Scholar]
  29. Narayan, O., Clements, J. E., Griffin, D. E. & Wolinsky, J. S. ( 1981; ). Neutralizing antibody spectrum determines the antigenic profiles of emerging mutants of visna virus. Infect Immun 32, 1045–1050.
    [Google Scholar]
  30. Narayan, O., Sheffer, D., Griffin, D. E., Clements, J. & Hess, J. ( 1984; ). Lack of neutralizing antibodies to caprine arthritis-encephalitis lentivirus in persistently infected goats can be overcome by immunization with inactivated Mycobacterium tuberculosis. J Virol 49, 349–355.
    [Google Scholar]
  31. Reitter, J. N., Means, R. E. & Desrosiers, R. C. ( 1998; ). A role for carbohydrates in immune evasion in AIDS. Nat Med 4, 679–684.[CrossRef]
    [Google Scholar]
  32. Rudensey, L. M., Kimata, J. T., Long, E. M., Chackerian, B. & Overbaugh, J. ( 1998; ). Changes in the extracellular envelope glycoprotein of variants that evolve during the course of simian immunodeficiency virus SIVMne infection affect neutralizing antibody recognition, syncytium formation, and macrophage tropism but not replication, cytopathicity, or CCR-5 coreceptor recognition. J Virol 72, 209–217.
    [Google Scholar]
  33. Sargan, D. R., Bennet, I. D., Cousens, C., Roy, D. J., Blacklaws, B. A., Dalziel, R. G., Watt, N. J. & McConnell, I. ( 1991; ). Nucleotide sequence of EV1, a British isolate of maedi-visna virus. J Gen Virol 72, 1893–1903.[CrossRef]
    [Google Scholar]
  34. Sigurdsson, B. ( 1954; ). Observations on three slow infections of sheep (I). Br Vet J 110, 255–270.
    [Google Scholar]
  35. Skraban, R., Matthiasdottir, S., Torsteinsdottir, S., Agnarsdottir, G., Gudmundsson, B., Georgsson, G., Meloen, R. H., Andresson, O. S., Staskus, K. A. & other authors ( 1999; ). Naturally occurring mutations within 39 amino acids in the envelope glycoprotein of maedi-visna virus alter the neutralization phenotype. J Virol 73, 8064–8072.
    [Google Scholar]
  36. Tschachler, E., Buchow, H., Gallo, R. C. & Reitz, M. S., Jr ( 1990; ). Functional contribution of cysteine residues to the human immunodeficiency virus type 1 envelope. J Virol 64, 2250–2259.
    [Google Scholar]
  37. Valas, S., Benoit, C., Guionaud, C., Perrin, G. & Mamoun, R. Z. ( 1997; ). North American and French caprine arthritis-encephalitis viruses emerge from ovine maedi-visna viruses. Virology 237, 307–318.[CrossRef]
    [Google Scholar]
  38. Valas, S., Benoit, C., Baudry, C., Perrin, G. & Mamoun, R. Z. ( 2000; ). Variability and immunogenicity of caprine arthritis-encephalitis virus surface glycoprotein. J Virol 74, 6178–6185.[CrossRef]
    [Google Scholar]
  39. Wei, X., Decker, J. M., Wang, S., Hui, H., Kappes, J. C., Wu, X., Salazar-Gonzalez, J. F., Salazar, M. G., Kilby, J. M. & other authors ( 2003; ). Antibody neutralization and escape by HIV-1. Nature 422, 307–312.[CrossRef]
    [Google Scholar]
  40. Wyatt, R. & Sodroski, J. ( 1998; ). The HIV-1 envelope glycoproteins: fusogens, antigens, and immunogens. Science 280, 1884–1888.[CrossRef]
    [Google Scholar]
  41. Wyatt, R., Kwong, P. D., Desjardins, E., Sweet, R. W., Robinson, J., Hendrickson, W. A. & Sodroski, J. G. ( 1998; ). The antigenic structure of the HIV gp120 envelope glycoprotein. Nature 393, 705–711.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.83410-0
Loading
/content/journal/jgv/10.1099/vir.0.83410-0
Loading

Data & Media loading...

Most cited articles

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error