Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1996 Dec;70(12):8518–8526. doi: 10.1128/jvi.70.12.8518-8526.1996

Roles of the auxiliary genes and AP-1 binding site in the long terminal repeat of feline immunodeficiency virus in the early stage of infection in cats.

Y Inoshima 1, M Kohmoto 1, Y Ikeda 1, H Yamada 1, Y Kawaguchi 1, K Tomonaga 1, T Miyazawa 1, C Kai 1, T Umemura 1, T Mikami 1
PMCID: PMC190943  PMID: 8970975

Abstract

To examine the roles of auxiliary genes and the AP-1 binding site in the long terminal repeat of feline immunodeficiency virus (FIV) in vivo, three mutant viruses, which are defective in the vif gene ([delta]vif), ORF-A gene (deltaORF-A), and AP-1 binding site (deltaAP-1), and wild-type virus as a positive control were separately inoculated into three specific-pathogen-free cats. These cats were assessed by measuring the number of proviral DNA copies in peripheral blood mononuclear cells (PBMCs), the CD4/CD8 ratio and antibody responses to FIV for 16 weeks and then examining histological changes at necropsy. Although viral DNAs were detected in PBMCs from all 12 cats to various degrees until 16 weeks postinoculation, no virus was recovered from PBMCs of cats infected with (delta)vif virus during the observation period. However, a very weak antibody response was induced in one cat infected with the (delta)vif virus. In contrast, despite the successful recovery of virus from both groups of cats infected with deltaORF-A and deltaAP-1 virus, antibody responses and decrease in the CD4/CD8 ratio in the groups were milder than those in cats infected with wild-type virus. Furthermore, the numbers of proviral DNA copies in PBMCs from the two groups were not able to reach the level in cats infected with wild-type virus during the observation period. From these results, we conclude that these mutant viruses are still infectious for cats but failed in efficient viral replication and suggest that these auxiliary genes and enhancer element are important or essential to full viral replication kinetics and presumably to full pathogenicity during the early stage of infection in vivo.

Full Text

The Full Text of this article is available as a PDF (551.7 KB).

Selected References

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

  1. Beebe A. M., Dua N., Faith T. G., Moore P. F., Pedersen N. C., Dandekar S. Primary stage of feline immunodeficiency virus infection: viral dissemination and cellular targets. J Virol. 1994 May;68(5):3080–3091. doi: 10.1128/jvi.68.5.3080-3091.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Chatis P. A., Holland C. A., Hartley J. W., Rowe W. P., Hopkins N. Role for the 3' end of the genome in determining disease specificity of Friend and Moloney murine leukemia viruses. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4408–4411. doi: 10.1073/pnas.80.14.4408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Clements J. E., Payne S. L. Molecular basis of the pathobiology of lentiviruses. Virus Res. 1994 May;32(2):97–109. doi: 10.1016/0168-1702(94)90037-x. [DOI] [PubMed] [Google Scholar]
  5. Courchamp F., Pontier D. Feline immunodeficiency virus: an epidemiological review. C R Acad Sci III. 1994 Dec;317(12):1123–1134. [PubMed] [Google Scholar]
  6. DesGroseillers L., Rassart E., Jolicoeur P. Thymotropism of murine leukemia virus is conferred by its long terminal repeat. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4203–4207. doi: 10.1073/pnas.80.14.4203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Elder J. H., Phillips T. R. Feline immunodeficiency virus as a model for development of molecular approaches to intervention strategies against lentivirus infections. Adv Virus Res. 1995;45:225–247. doi: 10.1016/s0065-3527(08)60062-7. [DOI] [PubMed] [Google Scholar]
  9. Elder J. H., Phillips T. R. Molecular properties of feline immunodeficiency virus (FIV). Infect Agents Dis. 1993 Dec;2(6):361–374. [PubMed] [Google Scholar]
  10. English R. V., Johnson C. M., Gebhard D. H., Tompkins M. B. In vivo lymphocyte tropism of feline immunodeficiency virus. J Virol. 1993 Sep;67(9):5175–5186. doi: 10.1128/jvi.67.9.5175-5186.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Furuya T., Hasegawa A., Saitoh M., Miyazawa T., Tohya Y., Hayami M., Takahashi E., Miki K., Mikami T. Expression of feline immunodeficiency virus gag gene in Escherichia coli. Arch Virol. 1992;122(3-4):383–390. doi: 10.1007/BF01317200. [DOI] [PubMed] [Google Scholar]
  12. Gabuzda D. H., Hess J. L., Small J. A., Clements J. E. Regulation of the visna virus long terminal repeat in macrophages involves cellular factors that bind sequences containing AP-1 sites. Mol Cell Biol. 1989 Jun;9(6):2728–2733. doi: 10.1128/mcb.9.6.2728. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gibbs J. S., Lackner A. A., Lang S. M., Simon M. A., Sehgal P. K., Daniel M. D., Desrosiers R. C. Progression to AIDS in the absence of a gene for vpr or vpx. J Virol. 1995 Apr;69(4):2378–2383. doi: 10.1128/jvi.69.4.2378-2383.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Harmache A., Vitu C., Russo P., Bouyac M., Hieblot C., Peveri P., Vigne R., Suzan M. The caprine arthritis encephalitis virus tat gene is dispensable for efficient viral replication in vitro and in vivo. J Virol. 1995 Sep;69(9):5445–5454. doi: 10.1128/jvi.69.9.5445-5454.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Heath S. L., Tew J. G., Tew J. G., Szakal A. K., Burton G. F. Follicular dendritic cells and human immunodeficiency virus infectivity. Nature. 1995 Oct 26;377(6551):740–744. doi: 10.1038/377740a0. [DOI] [PubMed] [Google Scholar]
  16. Hess J. L., Pyper J. M., Clements J. E. Nucleotide sequence and transcriptional activity of the caprine arthritis-encephalitis virus long terminal repeat. J Virol. 1986 Nov;60(2):385–393. doi: 10.1128/jvi.60.2.385-393.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hoch J., Lang S. M., Weeger M., Stahl-Hennig C., Coulibaly C., Dittmer U., Hunsmann G., Fuchs D., Müller J., Sopper S. vpr deletion mutant of simian immunodeficiency virus induces AIDS in rhesus monkeys. J Virol. 1995 Aug;69(8):4807–4813. doi: 10.1128/jvi.69.8.4807-4813.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Huang L. M., Joshi A., Willey R., Orenstein J., Jeang K. T. Human immunodeficiency viruses regulated by alternative trans-activators: genetic evidence for a novel non-transcriptional function of Tat in virion infectivity. EMBO J. 1994 Jun 15;13(12):2886–2896. doi: 10.1002/j.1460-2075.1994.tb06583.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Inoshima Y., Tomonaga K., Ikeda Y., Miyazawa T., Mikami T. Quantification of feline immunodeficiency virus (FIV) proviral DNA in peripheral blood mononuclear cells of cats infected with Japanese strains of FIV. J Vet Med Sci. 1995 Jun;57(3):487–492. doi: 10.1292/jvms.57.487. [DOI] [PubMed] [Google Scholar]
  20. Karczewski M. K., Strebel K. Cytoskeleton association and virion incorporation of the human immunodeficiency virus type 1 Vif protein. J Virol. 1996 Jan;70(1):494–507. doi: 10.1128/jvi.70.1.494-507.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kawaguchi Y., Miyazawa T., Tohya Y., Takahashi E., Mikami T. Quantification of feline immunodeficiency virus in a newly established feline T-lymphoblastoid cell line (MYA-1 cells). Arch Virol. 1990;111(3-4):269–273. doi: 10.1007/BF01311061. [DOI] [PubMed] [Google Scholar]
  22. Kawaguchi Y., Norimine J., Miyazawa T., Kai C., Mikami T. Sequences within the feline immunodeficiency virus long terminal repeat that regulate gene expression and respond to activation by feline herpesvirus type 1. Virology. 1992 Sep;190(1):465–468. doi: 10.1016/0042-6822(92)91235-m. [DOI] [PubMed] [Google Scholar]
  23. Kestler H. W., 3rd, Ringler D. J., Mori K., Panicali D. L., Sehgal P. K., Daniel M. D., Desrosiers R. C. Importance of the nef gene for maintenance of high virus loads and for development of AIDS. Cell. 1991 May 17;65(4):651–662. doi: 10.1016/0092-8674(91)90097-i. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Lang S. M., Weeger M., Stahl-Hennig C., Coulibaly C., Hunsmann G., Müller J., Müller-Hermelink H., Fuchs D., Wachter H., Daniel M. M. Importance of vpr for infection of rhesus monkeys with simian immunodeficiency virus. J Virol. 1993 Feb;67(2):902–912. doi: 10.1128/jvi.67.2.902-912.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lenz J., Celander D., Crowther R. L., Patarca R., Perkins D. W., Haseltine W. A. Determination of the leukaemogenicity of a murine retrovirus by sequences within the long terminal repeat. 1984 Mar 29-Apr 4Nature. 308(5958):467–470. doi: 10.1038/308467a0. [DOI] [PubMed] [Google Scholar]
  27. Luznik L., Kraus G., Guatelli J., Richman D., Wong-Staal F. Tat-independent replication of human immunodeficiency viruses. J Clin Invest. 1995 Jan;95(1):328–332. doi: 10.1172/JCI117660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Maki N., Miyazawa T., Fukasawa M., Hasegawa A., Hayami M., Miki K., Mikami T. Molecular characterization and heterogeneity of feline immunodeficiency virus isolates. Arch Virol. 1992;123(1-2):29–45. doi: 10.1007/BF01317136. [DOI] [PubMed] [Google Scholar]
  29. Michael N. L., Chang G., d'Arcy L. A., Ehrenberg P. K., Mariani R., Busch M. P., Birx D. L., Schwartz D. H. Defective accessory genes in a human immunodeficiency virus type 1-infected long-term survivor lacking recoverable virus. J Virol. 1995 Jul;69(7):4228–4236. doi: 10.1128/jvi.69.7.4228-4236.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Miyazawa T., Furuya T., Itagaki S., Tohya Y., Takahashi E., Mikami T. Establishment of a feline T-lymphoblastoid cell line highly sensitive for replication of feline immunodeficiency virus. Arch Virol. 1989;108(1-2):131–135. doi: 10.1007/BF01313750. [DOI] [PubMed] [Google Scholar]
  31. Miyazawa T., Inoshima Y., Kohmoto M., Ikeda Y., Mikami T. Growth properties of a feline immunodeficiency virus mutant which lacks an AP-1 binding site in primary peripheral blood mononuclear cells. J Vet Med Sci. 1994 Oct;56(5):869–872. doi: 10.1292/jvms.56.869. [DOI] [PubMed] [Google Scholar]
  32. Miyazawa T., Kohmoto M., Kawaguchi Y., Tomonaga K., Toyosaki T., Ikuta K., Adachi A., Mikami T. The AP-1 binding site in the feline immunodeficiency virus long terminal repeat is not required for virus replication in feline T lymphocytes. J Gen Virol. 1993 Aug;74(Pt 8):1573–1580. doi: 10.1099/0022-1317-74-8-1573. [DOI] [PubMed] [Google Scholar]
  33. Miyazawa T., Tomonaga K., Kawaguchi Y., Mikami T. The genome of feline immunodeficiency virus. Arch Virol. 1994;134(3-4):221–234. doi: 10.1007/BF01310563. [DOI] [PubMed] [Google Scholar]
  34. Narayan O., Clements J. E. Biology and pathogenesis of lentiviruses. J Gen Virol. 1989 Jul;70(Pt 7):1617–1639. doi: 10.1099/0022-1317-70-7-1617. [DOI] [PubMed] [Google Scholar]
  35. Oberste M. S., Gonda M. A. Conservation of amino-acid sequence motifs in lentivirus Vif proteins. Virus Genes. 1992 Jan;6(1):95–102. doi: 10.1007/BF01703760. [DOI] [PubMed] [Google Scholar]
  36. 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]
  37. 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]
  38. Reddy T. R., Kraus G., Yamada O., Looney D. J., Suhasini M., Wong-Staal F. Comparative analyses of human immunodeficiency virus type 1 (HIV-1) and HIV-2 Vif mutants. J Virol. 1995 Jun;69(6):3549–3553. doi: 10.1128/jvi.69.6.3549-3553.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Shacklett B. L., Luciw P. A. Analysis of the vif gene of feline immunodeficiency virus. Virology. 1994 Nov 1;204(2):860–867. doi: 10.1006/viro.1994.1609. [DOI] [PubMed] [Google Scholar]
  40. Shih D. S., Carruth L. M., Anderson M., Clements J. E. Involvement of FOS and JUN in the activation of visna virus gene expression in macrophages through an AP-1 site in the viral LTR. Virology. 1992 Sep;190(1):84–91. doi: 10.1016/0042-6822(92)91194-y. [DOI] [PubMed] [Google Scholar]
  41. Simon J. H., Southerling T. E., Peterson J. C., Meyer B. E., Malim M. H. Complementation of vif-defective human immunodeficiency virus type 1 by primate, but not nonprimate, lentivirus vif genes. J Virol. 1995 Jul;69(7):4166–4172. doi: 10.1128/jvi.69.7.4166-4172.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Sparger E. E., Beebe A. M., Dua N., Himathongkam S., Elder J. H., Torten M., Higgins J. Infection of cats with molecularly cloned and biological isolates of the feline immunodeficiency virus. Virology. 1994 Dec;205(2):546–553. doi: 10.1006/viro.1994.1677. [DOI] [PubMed] [Google Scholar]
  43. Sparger E. E., Shacklett B. L., Renshaw-Gegg L., Barry P. A., Pedersen N. C., Elder J. H., Luciw P. A. Regulation of gene expression directed by the long terminal repeat of the feline immunodeficiency virus. Virology. 1992 Mar;187(1):165–177. doi: 10.1016/0042-6822(92)90305-9. [DOI] [PubMed] [Google Scholar]
  44. Thompson F. J., Elder J., Neil J. C. Cis- and trans-regulation of feline immunodeficiency virus: identification of functional binding sites in the long terminal repeat. J Gen Virol. 1994 Mar;75(Pt 3):545–554. doi: 10.1099/0022-1317-75-3-545. [DOI] [PubMed] [Google Scholar]
  45. Tomonaga K., Mikami T. Molecular biology of the feline immunodeficiency virus auxiliary genes. J Gen Virol. 1996 Aug;77(Pt 8):1611–1621. doi: 10.1099/0022-1317-77-8-1611. [DOI] [PubMed] [Google Scholar]
  46. Tomonaga K., Miyazawa T., Sakuragi J., Mori T., Adachi A., Mikami T. The feline immunodeficiency virus ORF-A gene facilitates efficient viral replication in established T-cell lines and peripheral blood lymphocytes. J Virol. 1993 Oct;67(10):5889–5895. doi: 10.1128/jvi.67.10.5889-5895.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Tomonaga K., Norimine J., Shin Y. S., Fukasawa M., Miyazawa T., Adachi A., Toyosaki T., Kawaguchi Y., Kai C., Mikami T. Identification of a feline immunodeficiency virus gene which is essential for cell-free virus infectivity. J Virol. 1992 Oct;66(10):6181–6185. doi: 10.1128/jvi.66.10.6181-6185.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Toyosaki T., Miyazawa T., Furuya T., Tomonaga K., Shin Y. S., Okita M., Kawaguchi Y., Kai C., Mori S., Mikami T. Localization of the viral antigen of feline immunodeficiency virus in the lymph nodes of cats at the early stage of infection. Arch Virol. 1993;131(3-4):335–347. doi: 10.1007/BF01378636. [DOI] [PubMed] [Google Scholar]
  49. Waters A. K., De Parseval A. P., Lerner D. L., Neil J. C., Thompson F. J., Elder J. H. Influence of ORF2 on host cell tropism of feline immunodeficiency virus. Virology. 1996 Jan 1;215(1):10–16. doi: 10.1006/viro.1996.0002. [DOI] [PubMed] [Google Scholar]

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

RESOURCES