Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1997 Jun;71(6):4241–4253. doi: 10.1128/jvi.71.6.4241-4253.1997

Genetic diversity of feline immunodeficiency virus: dual infection, recombination, and distinct evolutionary rates among envelope sequence clades.

M H Bachmann 1, C Mathiason-Dubard 1, G H Learn 1, A G Rodrigo 1, D L Sodora 1, P Mazzetti 1, E A Hoover 1, J I Mullins 1
PMCID: PMC191639  PMID: 9151811

Abstract

For the rapid genetic analysis of feline immunodeficiency virus (FIV), we developed a heteroduplex mobility assay (HMA) that utilizes a PCR-amplified fragment of the FIV envelope gene spanning the third and fourth variable regions of the envelope surface protein coding sequence. Viral sequences were successfully amplified from blood specimens from 98 naturally infected cats from Australia, Canada, Germany, Italy, South Africa, and the United States. Eighty were clearly assignable to the A or B envelope sequence subtypes. Three belonged to subtype C, one was dually infected with viruses harboring the A and B env subtypes, and several were categorized as outliers to any of the established subtypes or as probable intersubtype recombinants. Some geographic clustering was evident, with subtypes A and B found in greater frequency in the western and eastern regions of the United States, respectively. Subtypes A, B, and C were found on more than one continent, and countries with more than two samples analyzed contained at least two subtypes. The broadest representation of subtypes was found in Munich, Germany, where three subtypes and one virus that was not classifiable by HMA were found. Thirteen samples were selected for DNA sequence determination over the same region of env used for HMA. Analysis of all available FIV env sequences from this and previous studies revealed the existence of recombinant viruses generated from subtype A/B, B/D, and A/C envelope gene sequences. Subtype A env sequences were less diverse than subtype B sequences, although both groups had well-supported clusters. Furthermore, the mutational pattern giving rise to diversification in the two subtypes differed, with the subtype A viruses showing half as many synonymous site mutations compared to subtype B yet showing similar levels of nonsynonymous site changes. These results are consistent with the hypothesis that FIV-B is an older virus group and is possibly more host adapted than FIV-A.

Full Text

The Full Text of this article is available as a PDF (1.1 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bendinelli M., Pistello M., Lombardi S., Poli A., Garzelli C., Matteucci D., Ceccherini-Nelli L., Malvaldi G., Tozzini F. Feline immunodeficiency virus: an interesting model for AIDS studies and an important cat pathogen. Clin Microbiol Rev. 1995 Jan;8(1):87–112. doi: 10.1128/cmr.8.1.87. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brown E. W., Yuhki N., Packer C., O'Brien S. J. A lion lentivirus related to feline immunodeficiency virus: epidemiologic and phylogenetic aspects. J Virol. 1994 Sep;68(9):5953–5968. doi: 10.1128/jvi.68.9.5953-5968.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brown W. C., Bissey L., Logan K. S., Pedersen N. C., Elder J. H., Collisson E. W. Feline immunodeficiency virus infects both CD4+ and CD8+ T lymphocytes. J Virol. 1991 Jun;65(6):3359–3364. doi: 10.1128/jvi.65.6.3359-3364.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brunner D., Pedersen N. C. Infection of peritoneal macrophages in vitro and in vivo with feline immunodeficiency virus. J Virol. 1989 Dec;63(12):5483–5488. doi: 10.1128/jvi.63.12.5483-5488.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. De Wolf F., Hogervorst E., Goudsmit J., Fenyö E. M., Rübsamen-Waigmann H., Holmes H., Galvao-Castro B., Karita E., Wasi C., Sempala S. D. Syncytium-inducing and non-syncytium-inducing capacity of human immunodeficiency virus type 1 subtypes other than B: phenotypic and genotypic characteristics. WHO Network for HIV Isolation and Characterization. AIDS Res Hum Retroviruses. 1994 Nov;10(11):1387–1400. doi: 10.1089/aid.1994.10.1387. [DOI] [PubMed] [Google Scholar]
  6. Delwart E. L., Herring B., Rodrigo A. G., Mullins J. I. Genetic subtyping of human immunodeficiency virus using a heteroduplex mobility assay. PCR Methods Appl. 1995 Apr;4(5):S202–S216. doi: 10.1101/gr.4.5.s202. [DOI] [PubMed] [Google Scholar]
  7. Delwart E. L., Sheppard H. W., Walker B. D., Goudsmit J., Mullins J. I. Human immunodeficiency virus type 1 evolution in vivo tracked by DNA heteroduplex mobility assays. J Virol. 1994 Oct;68(10):6672–6683. doi: 10.1128/jvi.68.10.6672-6683.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Delwart E. L., Shpaer E. G., Louwagie J., McCutchan F. E., Grez M., Rübsamen-Waigmann H., Mullins J. I. Genetic relationships determined by a DNA heteroduplex mobility assay: analysis of HIV-1 env genes. Science. 1993 Nov 19;262(5137):1257–1261. doi: 10.1126/science.8235655. [DOI] [PubMed] [Google Scholar]
  9. Diehl L. J., Mathiason-Dubard C. K., O'Neil L. L., Obert L. A., Hoover E. A. Induction of accelerated feline immunodeficiency virus disease by acute-phase virus passage. J Virol. 1995 Oct;69(10):6149–6157. doi: 10.1128/jvi.69.10.6149-6157.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dow S. W., Poss M. L., Hoover E. A. Feline immunodeficiency virus: a neurotropic lentivirus. J Acquir Immune Defic Syndr. 1990;3(7):658–668. [PubMed] [Google Scholar]
  11. English R. V., Nelson P., Johnson C. M., Nasisse M., Tompkins W. A., Tompkins M. B. Development of clinical disease in cats experimentally infected with feline immunodeficiency virus. J Infect Dis. 1994 Sep;170(3):543–552. doi: 10.1093/infdis/170.3.543. [DOI] [PubMed] [Google Scholar]
  12. Fitch W. M., Margoliash E. Construction of phylogenetic trees. Science. 1967 Jan 20;155(3760):279–284. doi: 10.1126/science.155.3760.279. [DOI] [PubMed] [Google Scholar]
  13. Fuchs A., Binzel L., Lonsdorfer M. Epidemiologie der FeLV- und FIV-Infektion in der Bundesrepublik Deutschland. Tierarztl Prax. 1994 Jun;22(3):273–277. [PubMed] [Google Scholar]
  14. Gao F., Yue L., Robertson D. L., Hill S. C., Hui H., Biggar R. J., Neequaye A. E., Whelan T. M., Ho D. D., Shaw G. M. Genetic diversity of human immunodeficiency virus type 2: evidence for distinct sequence subtypes with differences in virus biology. J Virol. 1994 Nov;68(11):7433–7447. doi: 10.1128/jvi.68.11.7433-7447.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ho D. D., Neumann A. U., Perelson A. S., Chen W., Leonard J. M., Markowitz M. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature. 1995 Jan 12;373(6510):123–126. doi: 10.1038/373123a0. [DOI] [PubMed] [Google Scholar]
  16. Ho D. D. Viral counts count in HIV infection. Science. 1996 May 24;272(5265):1124–1125. doi: 10.1126/science.272.5265.1124. [DOI] [PubMed] [Google Scholar]
  17. Hosie M. J., Osborne R., Yamamoto J. K., Neil J. C., Jarrett O. Protection against homologous but not heterologous challenge induced by inactivated feline immunodeficiency virus vaccines. J Virol. 1995 Feb;69(2):1253–1255. doi: 10.1128/jvi.69.2.1253-1255.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hosie M. J., Robertson C., Jarrett O. Prevalence of feline leukaemia virus and antibodies to feline immunodeficiency virus in cats in the United Kingdom. Vet Rec. 1989 Sep 9;125(11):293–297. doi: 10.1136/vr.125.11.293. [DOI] [PubMed] [Google Scholar]
  19. Ishida T., Washizu T., Toriyabe K., Motoyoshi S., Tomoda I., Pedersen N. C. Feline immunodeficiency virus infection in cats of Japan. J Am Vet Med Assoc. 1989 Jan 15;194(2):221–225. [PubMed] [Google Scholar]
  20. Kakinuma S., Motokawa K., Hohdatsu T., Yamamoto J. K., Koyama H., Hashimoto H. Nucleotide sequence of feline immunodeficiency virus: classification of Japanese isolates into two subtypes which are distinct from non-Japanese subtypes. J Virol. 1995 Jun;69(6):3639–3646. doi: 10.1128/jvi.69.6.3639-3646.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Katz R. A., Skalka A. M. Generation of diversity in retroviruses. Annu Rev Genet. 1990;24:409–445. doi: 10.1146/annurev.ge.24.120190.002205. [DOI] [PubMed] [Google Scholar]
  22. Kiyomasu T., Miyazawa T., Furuya T., Shibata R., Sakai H., Sakuragi J., Fukasawa M., Maki N., Hasegawa A., Mikami T. Identification of feline immunodeficiency virus rev gene activity. J Virol. 1991 Aug;65(8):4539–4542. doi: 10.1128/jvi.65.8.4539-4542.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kumar S., Tamura K., Nei M. MEGA: Molecular Evolutionary Genetics Analysis software for microcomputers. Comput Appl Biosci. 1994 Apr;10(2):189–191. doi: 10.1093/bioinformatics/10.2.189. [DOI] [PubMed] [Google Scholar]
  24. Langley R. J., Hirsch V. M., O'Brien S. J., Adger-Johnson D., Goeken R. M., Olmsted R. A. Nucleotide sequence analysis of puma lentivirus (PLV-14): genomic organization and relationship to other lentiviruses. Virology. 1994 Aug 1;202(2):853–864. doi: 10.1006/viro.1994.1407. [DOI] [PubMed] [Google Scholar]
  25. Meyerhans A., Vartanian J. P., Wain-Hobson S. DNA recombination during PCR. Nucleic Acids Res. 1990 Apr 11;18(7):1687–1691. doi: 10.1093/nar/18.7.1687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Miyazawa T., Fukasawa M., Hasegawa A., Maki N., Ikuta K., Takahashi E., Hayami M., Mikami T. Molecular cloning of a novel isolate of feline immunodeficiency virus biologically and genetically different from the original U.S. isolate. J Virol. 1991 Mar;65(3):1572–1577. doi: 10.1128/jvi.65.3.1572-1577.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Morikawa S., Lutz H., Aubert A., Bishop D. H. Identification of conserved and variable regions in the envelope glycoprotein sequences of two feline immunodeficiency viruses isolated in Zurich, Switzerland. Virus Res. 1991 Sep;21(1):53–63. doi: 10.1016/0168-1702(91)90071-3. [DOI] [PubMed] [Google Scholar]
  28. Norimine J., Miyazawa T., Kawaguchi Y., Tomonaga K., Shin Y. S., Toyosaki T., Kohmoto M., Niikura M., Tohya Y., Mikami T. Feline CD4 molecules expressed on feline non-lymphoid cell lines are not enough for productive infection of highly lymphotropic feline immunodeficiency virus isolates. Arch Virol. 1993;130(1-2):171–178. doi: 10.1007/BF01319005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Okada S., Pu R., Young E., Stoffs W. V., Yamamoto J. K. Superinfection of cats with feline immunodeficiency virus subtypes A and B. AIDS Res Hum Retroviruses. 1994 Dec;10(12):1739–1746. doi: 10.1089/aid.1994.10.1739. [DOI] [PubMed] [Google Scholar]
  30. Olmsted R. A., Hirsch V. M., Purcell R. H., Johnson P. R. Nucleotide sequence analysis of feline immunodeficiency virus: genome organization and relationship to other lentiviruses. Proc Natl Acad Sci U S A. 1989 Oct;86(20):8088–8092. doi: 10.1073/pnas.86.20.8088. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Olmsted R. A., Langley R., Roelke M. E., Goeken R. M., Adger-Johnson D., Goff J. P., Albert J. P., Packer C., Laurenson M. K., Caro T. M. Worldwide prevalence of lentivirus infection in wild feline species: epidemiologic and phylogenetic aspects. J Virol. 1992 Oct;66(10):6008–6018. doi: 10.1128/jvi.66.10.6008-6018.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Pancino G., Fossati I., Chappey C., Castelot S., Hurtrel B., Moraillon A., Klatzmann D., Sonigo P. Structure and variations of feline immunodeficiency virus envelope glycoproteins. Virology. 1993 Feb;192(2):659–662. doi: 10.1006/viro.1993.1083. [DOI] [PubMed] [Google Scholar]
  33. Pedersen N. C., Ho E. W., Brown M. L., Yamamoto J. K. Isolation of a T-lymphotropic virus from domestic cats with an immunodeficiency-like syndrome. Science. 1987 Feb 13;235(4790):790–793. doi: 10.1126/science.3643650. [DOI] [PubMed] [Google Scholar]
  34. Pedersen N. C., Yamamoto J. K., Ishida T., Hansen H. Feline immunodeficiency virus infection. Vet Immunol Immunopathol. 1989 May;21(1):111–129. doi: 10.1016/0165-2427(89)90134-7. [DOI] [PubMed] [Google Scholar]
  35. Phillips T. R., Talbott R. L., Lamont C., Muir S., Lovelace K., Elder J. H. Comparison of two host cell range variants of feline immunodeficiency virus. J Virol. 1990 Oct;64(10):4605–4613. doi: 10.1128/jvi.64.10.4605-4613.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Rigby M. A., Holmes E. C., Pistello M., Mackay A., Brown A. J., Neil J. C. Evolution of structural proteins of feline immunodeficiency virus: molecular epidemiology and evidence of selection for change. J Gen Virol. 1993 Mar;74(Pt 3):425–436. doi: 10.1099/0022-1317-74-3-425. [DOI] [PubMed] [Google Scholar]
  37. Robertson D. L., Hahn B. H., Sharp P. M. Recombination in AIDS viruses. J Mol Evol. 1995 Mar;40(3):249–259. doi: 10.1007/BF00163230. [DOI] [PubMed] [Google Scholar]
  38. Robertson D. L., Sharp P. M., McCutchan F. E., Hahn B. H. Recombination in HIV-1. Nature. 1995 Mar 9;374(6518):124–126. doi: 10.1038/374124b0. [DOI] [PubMed] [Google Scholar]
  39. Sabino E. C., Shpaer E. G., Morgado M. G., Korber B. T., Diaz R. S., Bongertz V., Cavalcante S., Galvão-Castro B., Mullins J. I., Mayer A. Identification of human immunodeficiency virus type 1 envelope genes recombinant between subtypes B and F in two epidemiologically linked individuals from Brazil. J Virol. 1994 Oct;68(10):6340–6346. doi: 10.1128/jvi.68.10.6340-6346.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Saitou N., Nei M. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol. 1987 Jul;4(4):406–425. doi: 10.1093/oxfordjournals.molbev.a040454. [DOI] [PubMed] [Google Scholar]
  41. Shpaer E. G., Mullins J. I. Rates of amino acid change in the envelope protein correlate with pathogenicity of primate lentiviruses. J Mol Evol. 1993 Jul;37(1):57–65. doi: 10.1007/BF00170462. [DOI] [PubMed] [Google Scholar]
  42. Siebelink K. H., Chu I. H., Rimmelzwaan G. F., Weijer K., Osterhaus A. D., Bosch M. L. Isolation and partial characterization of infectious molecular clones of feline immunodeficiency virus obtained directly from bone marrow DNA of a naturally infected cat. J Virol. 1992 Feb;66(2):1091–1097. doi: 10.1128/jvi.66.2.1091-1097.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Siepel A. C., Halpern A. L., Macken C., Korber B. T. A computer program designed to screen rapidly for HIV type 1 intersubtype recombinant sequences. AIDS Res Hum Retroviruses. 1995 Nov;11(11):1413–1416. doi: 10.1089/aid.1995.11.1413. [DOI] [PubMed] [Google Scholar]
  44. Smith S. W., Overbeek R., Woese C. R., Gilbert W., Gillevet P. M. The genetic data environment an expandable GUI for multiple sequence analysis. Comput Appl Biosci. 1994 Dec;10(6):671–675. doi: 10.1093/bioinformatics/10.6.671. [DOI] [PubMed] [Google Scholar]
  45. Smith T. F., Srinivasan A., Schochetman G., Marcus M., Myers G. The phylogenetic history of immunodeficiency viruses. Nature. 1988 Jun 9;333(6173):573–575. doi: 10.1038/333573a0. [DOI] [PubMed] [Google Scholar]
  46. Sodora D. L., Courcelle J., Brojatsch J., Berson A., Wang Y. C., Dow S. W., Hoover E. A., Mullins J. I. Analysis of a feline immunodeficiency virus provirus reveals patterns of gene sequence conservation distinct from human immunodeficiency virus type 1. AIDS Res Hum Retroviruses. 1995 Apr;11(4):531–533. doi: 10.1089/aid.1995.11.531. [DOI] [PubMed] [Google Scholar]
  47. Sodora D. L., Shpaer E. G., Kitchell B. E., Dow S. W., Hoover E. A., Mullins J. I. Identification of three feline immunodeficiency virus (FIV) env gene subtypes and comparison of the FIV and human immunodeficiency virus type 1 evolutionary patterns. J Virol. 1994 Apr;68(4):2230–2238. doi: 10.1128/jvi.68.4.2230-2238.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Talbott R. L., Sparger E. E., Lovelace K. M., Fitch W. M., Pedersen N. C., Luciw P. A., Elder J. H. Nucleotide sequence and genomic organization of feline immunodeficiency virus. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5743–5747. doi: 10.1073/pnas.86.15.5743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Temin H. M. Sex and recombination in retroviruses. Trends Genet. 1991 Mar;7(3):71–74. doi: 10.1016/0168-9525(91)90272-R. [DOI] [PubMed] [Google Scholar]
  50. Thompson J. D., Higgins D. G., Gibson T. J. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994 Nov 11;22(22):4673–4680. doi: 10.1093/nar/22.22.4673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Verschoor E. J., Hulskotte E. G., Ederveen J., Koolen M. J., Horzinek M. C., Rottier P. J. Post-translational processing of the feline immunodeficiency virus envelope precursor protein. Virology. 1993 Mar;193(1):433–438. doi: 10.1006/viro.1993.1140. [DOI] [PubMed] [Google Scholar]
  52. Wei X., Ghosh S. K., Taylor M. E., Johnson V. A., Emini E. A., Deutsch P., Lifson J. D., Bonhoeffer S., Nowak M. A., Hahn B. H. Viral dynamics in human immunodeficiency virus type 1 infection. Nature. 1995 Jan 12;373(6510):117–122. doi: 10.1038/373117a0. [DOI] [PubMed] [Google Scholar]
  53. Willett B. J., Hosie M. J., Neil J. C., Turner J. D., Hoxie J. A. Common mechanism of infection by lentiviruses. Nature. 1997 Feb 13;385(6617):587–587. doi: 10.1038/385587a0. [DOI] [PubMed] [Google Scholar]
  54. Yamamoto J. K., Hansen H., Ho E. W., Morishita T. Y., Okuda T., Sawa T. R., Nakamura R. M., Pedersen N. C. Epidemiologic and clinical aspects of feline immunodeficiency virus infection in cats from the continental United States and Canada and possible mode of transmission. J Am Vet Med Assoc. 1989 Jan 15;194(2):213–220. [PubMed] [Google Scholar]
  55. Yamamoto J. K., Hohdatsu T., Olmsted R. A., Pu R., Louie H., Zochlinski H. A., Acevedo V., Johnson H. M., Soulds G. A., Gardner M. B. Experimental vaccine protection against homologous and heterologous strains of feline immunodeficiency virus. J Virol. 1993 Jan;67(1):601–605. doi: 10.1128/jvi.67.1.601-605.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Yang J. S., English R. V., Ritchey J. W., Davidson M. G., Wasmoen T., Levy J. K., Gebhard D. H., Tompkins M. B., Tompkins W. A. Molecularly cloned feline immunodeficiency virus NCSU1 JSY3 induces immunodeficiency in specific-pathogen-free cats. J Virol. 1996 May;70(5):3011–3017. doi: 10.1128/jvi.70.5.3011-3017.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES