1887

Journal of General Virology

Volume 91, Issue 1

Neutralization of feline immunodeficiency virus by antibodies targeting the V5 loop of Env Open Access

Abstract

Neutralizing antibodies (NAbs) play a vital role in vaccine-induced protection against infection with feline immunodeficiency virus (FIV). However, little is known about the appropriate presentation of neutralization epitopes in order to induce NAbs effectively; the majority of the antibodies that are induced are directed against non-neutralizing epitopes. Here, we demonstrate that a subtype B strain of FIV, designated NG4, escapes autologous NAbs, but may be rendered neutralization-sensitive following the insertion of two amino acids, KT, at positions 556–557 in the fifth hypervariable (V5) loop of the envelope glycoprotein. Consistent with the contribution of this motif to virus neutralization, an additional three subtype B strains retaining both residues at the same position were also neutralized by the NG4 serum, and serum from an unrelated cat (TOT1) targeted the same sequence in V5. Moreover, when the V5 loop of subtype B isolate KNG2, an isolate that was moderately resistant to neutralization by NG4 serum, was mutated to incorporate the KT motif, the virus was rendered sensitive to neutralization. These data suggest that, even in a polyclonal serum derived from FIV-infected cats following natural infection, the primary determinant of virus-neutralizing activity may be represented by a single, dominant epitope in V5.

  • Received:
  • Accepted:
  • Published Online:
© SGM
Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.015404-0
2010-01-01
2021-10-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/91/1/242.html?itemId=/content/journal/jgv/10.1099/vir.0.015404-0&mimeType=html&fmt=ahah

References

  1. Ackley, C. D., Yamamoto, J. K., Levy, N., Pedersen, N. C. & Cooper, M. D.(1990). Immunologic abnormalities in pathogen-free cats experimentally infected with feline immunodeficiency virus. J Virol 64, 5652–5655. [Google Scholar]
  2. Bachmann, M. H., Mathiason-Dubard, C., Learn, G. H., Rodrigo, A. G., Sodora, D. L., Mazzetti, P., Hoover, E. A. & Mullins, J. I.(1997). Genetic diversity of feline immunodeficiency virus: dual infection, recombination, and distinct evolutionary rates among envelope sequence clades. J Virol 71, 4241–4253. [Google Scholar]
  3. Bendinelli, M., Pistello, M., Lombardi, S., Poli, A., Garzelli, C., Matteucci, D., Ceccherini-Nelli, L., Malvaldi, G. & Tozzini, F.(1995). Feline immunodeficiency virus: an interesting model for AIDS studies and an important cat pathogen. Clin Microbiol Rev 8, 87–112. [Google Scholar]
  4. Bernstein, H. B., Tucker, S. P., Hunter, E., Schutzbach, J. S. & Compans, R. W.(1994). Human immunodeficiency virus type 1 envelope glycoprotein is modified by O-linked oligosaccharides. J Virol 68, 463–468. [Google Scholar]
  5. Binley, J. M., Wrin, T., Korber, B., Zwick, M. B., Wang, M., Chappey, C., Stiegler, G., Kunert, R., Zolla-Pazner, S. & other authors(2004). Comprehensive cross-clade neutralization analysis of a panel of anti-human immunodeficiency virus type 1 monoclonal antibodies. J Virol 78, 13232–13252.[CrossRef] [Google Scholar]
  6. Chiarantini, L., Matteucci, D., Pistello, M., Mancini, U., Mazzetti, P., Massi, C., Giannecchini, S., Lonetti, I., Magnani, M. & Bendinelli, M.(1998). AIDS vaccination studies using an ex vivo feline immunodeficiency virus model: homologous erythrocytes as a delivery system for preferential immunization with putative protective antigens. Clin Diagn Lab Immunol 5, 235–241. [Google Scholar]
  7. Connor, R. I., Chen, B. K., Choe, S. & Landau, N. R.(1995). Vpr is required for efficient replication of human immunodeficiency virus type-1 in mononuclear phagocytes. Virology 206, 935–944.[CrossRef] [Google Scholar]
  8. Dhillon, A. K., Donners, H., Pantophlet, R., Johnson, W. E., Decker, J. M., Shaw, G. M., Lee, F. H., Richman, D. D., Doms, R. W. & other authors(2007). Dissecting the neutralizing antibody specificities of broadly neutralizing sera from human immunodeficiency virus type 1-infected donors. J Virol 81, 6548–6562.[CrossRef] [Google Scholar]
  9. Elder, J. H., Dean, G. A., Hoover, E. A., Hoxie, J. A., Malim, M. H., Mathes, L., Neil, J. C., North, T. W., Sparger, E. & other authors(1998). Lessons from the cat: feline immunodeficiency virus as a tool to develop intervention strategies against human immunodeficiency virus type 1. AIDS Res Hum Retroviruses 14, 797–801.[CrossRef] [Google Scholar]
  10. English, R. V., Johnson, C. M., Gebhard, D. H. & Tompkins, M. B.(1993). In vivo lymphocyte tropism of feline immunodeficiency virus. J Virol 67, 5175–5186. [Google Scholar]
  11. Felsenstein, J.(1989).phylip – phylogeny inference package (version 3.2). Cladistics 5, 164–166. [Google Scholar]
  12. 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]
  13. Giannecchini, S., Matteucci, D., Ferrari, A., Pistello, M. & Bendinelli, M.(2001). Feline immunodeficiency virus-infected cat sera associated with the development of broad neutralization resistance in vivo drive similar reversions in vitro. J Virol 75, 8868–8873.[CrossRef] [Google Scholar]
  14. Hall, T. A.(1999). BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symp Ser 41, 95–98. [Google Scholar]
  15. Hosie, M. J. & Beatty, J. A.(2007). Vaccine protection against feline immunodeficiency virus: setting the challenge. Aust Vet J 85, 5–12.[CrossRef] [Google Scholar]
  16. Huang, X., Barchi, J. J., Jr, Lung, F. D., Roller, P. P., Nara, P. L., Muschik, J. & Garrity, R. R.(1997). Glycosylation affects both the three-dimensional structure and antibody binding properties of the HIV-1IIIB GP120 peptide RP135. Biochemistry 36, 10846–10856.[CrossRef] [Google Scholar]
  17. Johnson, C. M., Torres, B. A., Koyama, H. & Yamamoto, J. K.(1994). Tenth anniversary perspectives on AIDS. FIV as a model for AIDS vaccination. AIDS Res Hum Retroviruses 10, 225–228.[CrossRef] [Google Scholar]
  18. Labrijn, A. F., Poignard, P., Raja, A., Zwick, M. B., Delgado, K., Franti, M., Binley, J., Vivona, V., Grundner, C. & other authors(2003). Access of antibody molecules to the conserved coreceptor binding site on glycoprotein gp120 is sterically restricted on primary human immunodeficiency virus type 1. J Virol 77, 10557–10565.[CrossRef] [Google Scholar]
  19. Larkin, M. A., Blackshields, G., Brown, N. P., Chenna, R., McGettigan, P. A., McWilliam, H., Valentin, F., Wallace, I. M., Wilm, A. & other authors(2007).clustalw and clustal_x version 2.0. Bioinformatics 23, 2947–2948.[CrossRef] [Google Scholar]
  20. Lombardi, S., Garzelli, C., La Rosa, C., Zaccaro, L., Specter, S., Malvaldi, G., Tozzini, F., Esposito, F. & Bendinelli, M.(1993). Identification of a linear neutralization site within the third variable region of the feline immunodeficiency virus envelope. J Virol 67, 4742–4749. [Google Scholar]
  21. Miller, R. J., Cairns, J. S., Bridges, S. & Sarver, N.(2000). Human immunodeficiency virus and AIDS: insights from animal lentiviruses. J Virol 74, 7187–7195.[CrossRef] [Google Scholar]
  22. Okada, S., Pu, R., Young, E., Stoffs, W. V. & Yamamoto, J. K.(1994). Superinfection of cats with feline immunodeficiency virus subtypes A and B. AIDS Res Hum Retroviruses 10, 1739–1746.[CrossRef] [Google Scholar]
  23. Osborne, R., Rigby, M., Siebelink, K., Neil, J. C. & Jarrett, O.(1994). Virus neutralization reveals antigenic variation among feline immunodeficiency virus isolates. J Gen Virol 75, 3641–3645.[CrossRef] [Google Scholar]
  24. Pedersen, N. C., Ho, E. W., Brown, M. L. & Yamamoto, J. K.(1987). Isolation of a T-lymphotropic virus from domestic cats with an immunodeficiency syndrome. Science 235, 790–793.[CrossRef] [Google Scholar]
  25. Pistello, M., Cammarota, G., Nicoletti, E., Matteucci, D., Curcio, M., Del Mauro, D. & Bendinelli, M.(1997). Analysis of the genetic diversity and phylogenetic relationship of Italian isolates of feline immunodeficiency virus indicates a high prevalence and heterogeneity of subtype B. J Gen Virol 78, 2247–2257. [Google Scholar]
  26. Pistello, M., Matteucci, D., Giannecchini, S., Bonci, F., Sichi, O., Presciuttini, S. & Bendinelli, M.(2003). Evolution of two amino acid positions governing broad neutralization resistance in a strain of feline immunodeficiency virus over 7 years of persistence in cats. Clin Diagn Lab Immunol 10, 1109–1116. [Google Scholar]
  27. Richman, D. D., Wrin, T., Little, S. J. & Petropoulos, C. J.(2003). Rapid evolution of the neutralizing antibody response to HIV type 1 infection. Proc Natl Acad Sci U S A 100, 4144–4149.[CrossRef] [Google Scholar]
  28. Siebelink, K. H., Bosch, M. L., Rimmelzwaan, G. F., Meloen, R. H. & Osterhaus, A. D.(1995). Two different mutations in the envelope protein of feline immunodeficiency virus allow the virus to escape from neutralization by feline serum antibodies. Vet Immunol Immunopathol 46, 51–59.[CrossRef] [Google Scholar]
  29. Steinrigl, A. & Klein, D.(2003). Phylogenetic analysis of feline immunodeficiency virus in Central Europe: a prerequisite for vaccination and molecular diagnostics. J Gen Virol 84, 1301–1307.[CrossRef] [Google Scholar]
  30. Tamura, K., Dudley, J., Nei, M. & Kumar, S.(2007).mega4: molecular evolutionary genetics analysis (mega) software version 4.0. Mol Biol Evol 24, 1596–1599.[CrossRef] [Google Scholar]
  31. 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]
  32. Willett, B. J., McMonagle, E. L., Ridha, S. & Hosie, M. J.(2006). Differential utilization of CD134 as a functional receptor by diverse strains of feline immunodeficiency virus (FIV). J Virol 80, 3386–3394.[CrossRef] [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.015404-0
Loading
Neutralization of feline immunodeficiency virus by antibodies targeting the V5 loop of Env
J. Gen. Virol. 91, 242 (2010); https://doi.org/10.1099/vir.0.015404-0
/content/journal/jgv/10.1099/vir.0.015404-0
/content/journal/jgv/10.1099/vir.0.015404-0
Loading

Data & Media loading...

Supplements

vol. , part 1, pp. 242–249

Oligonucleotides used for site-directed mutagenesis of V5.

GenBank accession numbers for reference sequences and new sequences obtained in this study.

[ Single PDF file] (78 KB)

PDF

Most cited this month Most Cited RSS feed

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