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. 1995 Aug;69(8):4752–4757. doi: 10.1128/jvi.69.8.4752-4757.1995

A single mutation within the V3 envelope neutralization domain of feline immunodeficiency virus determines its tropism for CRFK cells.

E J Verschoor 1, L A Boven 1, H Blaak 1, A L van Vliet 1, M C Horzinek 1, A de Ronde 1
PMCID: PMC189284  PMID: 7609041

Abstract

Feline immunodeficiency virus (FIV) isolates differ in the ability to replicate in Crandell feline kidney (CRFK) cells. The difference in tropism between two variants of the Dutch isolate FIV-UT113 was studied by using molecular clones which contained the envelope genes of the variants in a background of the FIV-14 Petaluma sequence. Virus produced from clone pPET-113Th replicated in thymocytes, whereas virus from pPET-113Cr propagated in both thymocytes and CRFK cells, thereby reflecting the phenotypes of the parental variants. Exchange of envelope gene fragments showed that a 464-bp surface protein (SU)-encoding fragment encompassing the third variable region (V3) determines CRFK cell tropism. Sequence analysis of the exchanged fragments demonstrated two amino acid changes that led to an increase of the overall charge of the V3 domain: a G-->R transition at position 397 and a E-->K change at position 407. Mutational analysis of these residues revealed that the E-->K shift was responsible for the change in tropism, while the G-->R mutation improved the replication kinetics in CRFK cells. Mapping of a tropism determinant for FIV to a region which is also a major neutralization domain is reminiscent of human immunodeficiency virus type 1, in which a similar colocation was found.

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Selected References

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  1. Baldinotti F., Matteucci D., Mazzetti P., Giannelli C., Bandecchi P., Tozzini F., Bendinelli M. Serum neutralization of feline immunodeficiency virus is markedly dependent on passage history of the virus and host system. J Virol. 1994 Jul;68(7):4572–4579. doi: 10.1128/jvi.68.7.4572-4579.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Banapour B., Marthas M. L., Ramos R. A., Lohman B. L., Unger R. E., Gardner M. B., Pedersen N. C., Luciw P. A. Identification of viral determinants of macrophage tropism for simian immunodeficiency virus SIVmac. J Virol. 1991 Nov;65(11):5798–5805. doi: 10.1128/jvi.65.11.5798-5805.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  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. Crandell R. A., Fabricant C. G., Nelson-Rees W. A. Development, characterization, and viral susceptibility of a feline (Felis catus) renal cell line (CRFK). In Vitro. 1973 Nov-Dec;9(3):176–185. doi: 10.1007/BF02618435. [DOI] [PubMed] [Google Scholar]
  6. De Jong J. J., De Ronde A., Keulen W., Tersmette M., Goudsmit J. Minimal requirements for the human immunodeficiency virus type 1 V3 domain to support the syncytium-inducing phenotype: analysis by single amino acid substitution. J Virol. 1992 Nov;66(11):6777–6780. doi: 10.1128/jvi.66.11.6777-6780.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dow S. W., Dreitz M. J., Hoover E. A. Feline immunodeficiency virus neurotropism: evidence that astrocytes and microglia are the primary target cells. Vet Immunol Immunopathol. 1992 Dec;35(1-2):23–35. doi: 10.1016/0165-2427(92)90118-a. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Dragic T., Alizon M. Different requirements for membrane fusion mediated by the envelopes of human immunodeficiency virus types 1 and 2. J Virol. 1993 Apr;67(4):2355–2359. doi: 10.1128/jvi.67.4.2355-2359.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Egberink H. F., Ederveen J., Montelaro R. C., Pedersen N. C., Horzinek M. C., Koolen M. J. Intracellular proteins of feline immunodeficiency virus and their antigenic relationship with equine infectious anaemia virus proteins. J Gen Virol. 1990 Mar;71(Pt 3):739–743. doi: 10.1099/0022-1317-71-3-739. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Harrington R. D., Geballe A. P. Cofactor requirement for human immunodeficiency virus type 1 entry into a CD4-expressing human cell line. J Virol. 1993 Oct;67(10):5939–5947. doi: 10.1128/jvi.67.10.5939-5947.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hosie M. J., Willett B. J., Dunsford T. H., Jarrett O., Neil J. C. A monoclonal antibody which blocks infection with feline immunodeficiency virus identifies a possible non-CD4 receptor. J Virol. 1993 Mar;67(3):1667–1671. doi: 10.1128/jvi.67.3.1667-1671.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Javaherian K., Langlois A. J., Schmidt S., Kaufmann M., Cates N., Langedijk J. P., Meloen R. H., Desrosiers R. C., Burns D. P., Bolognesi D. P. The principal neutralization determinant of simian immunodeficiency virus differs from that of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1418–1422. doi: 10.1073/pnas.89.4.1418. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kohmoto M., Miyazawa T., Tomonaga K., Kawaguchi Y., Mori T., Tohya Y., Kai C., Mikami T. Comparison of biological properties of feline immunodeficiency virus isolates using recombinant chimeric viruses. J Gen Virol. 1994 Aug;75(Pt 8):1935–1942. doi: 10.1099/0022-1317-75-8-1935. [DOI] [PubMed] [Google Scholar]
  16. Kusumi K., Conway B., Cunningham S., Berson A., Evans C., Iversen A. K., Colvin D., Gallo M. V., Coutre S., Shpaer E. G. Human immunodeficiency virus type 1 envelope gene structure and diversity in vivo and after cocultivation in vitro. J Virol. 1992 Feb;66(2):875–885. doi: 10.1128/jvi.66.2.875-885.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lairmore M. D., Akita G. Y., Russell H. I., DeMartini J. C. Replication and cytopathic effects of ovine lentivirus strains in alveolar macrophages correlate with in vivo pathogenicity. J Virol. 1987 Dec;61(12):4038–4042. doi: 10.1128/jvi.61.12.4038-4042.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Levy J. A. Pathogenesis of human immunodeficiency virus infection. Microbiol Rev. 1993 Mar;57(1):183–289. doi: 10.1128/mr.57.1.183-289.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lombardi S., Garzelli C., La Rosa C., Zaccaro L., Specter S., Malvaldi G., Tozzini F., Esposito F., Bendinelli M. Identification of a linear neutralization site within the third variable region of the feline immunodeficiency virus envelope. J Virol. 1993 Aug;67(8):4742–4749. doi: 10.1128/jvi.67.8.4742-4749.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Olmsted R. A., Barnes A. K., Yamamoto J. K., Hirsch V. M., Purcell R. H., Johnson P. R. Molecular cloning of feline immunodeficiency virus. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2448–2452. doi: 10.1073/pnas.86.7.2448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. 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]
  23. Phillips T. R., Lamont C., Konings D. A., Shacklett B. L., Hamson C. A., Luciw P. A., Elder J. H. Identification of the Rev transactivation and Rev-responsive elements of feline immunodeficiency virus. J Virol. 1992 Sep;66(9):5464–5471. doi: 10.1128/jvi.66.9.5464-5471.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. 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]
  25. Schuitemaker H., Koot M., Kootstra N. A., Dercksen M. W., de Goede R. E., van Steenwijk R. P., Lange J. M., Schattenkerk J. K., Miedema F., Tersmette M. Biological phenotype of human immunodeficiency virus type 1 clones at different stages of infection: progression of disease is associated with a shift from monocytotropic to T-cell-tropic virus population. J Virol. 1992 Mar;66(3):1354–1360. doi: 10.1128/jvi.66.3.1354-1360.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Shioda T., Levy J. A., Cheng-Mayer C. Small amino acid changes in the V3 hypervariable region of gp120 can affect the T-cell-line and macrophage tropism of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9434–9438. doi: 10.1073/pnas.89.20.9434. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Shioda T., Oka S., Ida S., Nokihara K., Toriyoshi H., Mori S., Takebe Y., Kimura S., Shimada K., Nagai Y. A naturally occurring single basic amino acid substitution in the V3 region of the human immunodeficiency virus type 1 env protein alters the cellular host range and antigenic structure of the virus. J Virol. 1994 Dec;68(12):7689–7696. doi: 10.1128/jvi.68.12.7689-7696.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. 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]
  29. Tersmette M., Gruters R. A., de Wolf F., de Goede R. E., Lange J. M., Schellekens P. T., Goudsmit J., Huisman H. G., Miedema F. Evidence for a role of virulent human immunodeficiency virus (HIV) variants in the pathogenesis of acquired immunodeficiency syndrome: studies on sequential HIV isolates. J Virol. 1989 May;63(5):2118–2125. doi: 10.1128/jvi.63.5.2118-2125.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. 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]
  31. Willett B. J., Hosie M. J., Jarrett O., Neil J. C. Identification of a putative cellular receptor for feline immunodeficiency virus as the feline homologue of CD9. Immunology. 1994 Feb;81(2):228–233. [PMC free article] [PubMed] [Google Scholar]
  32. de Jong J. J., Goudsmit J., Keulen W., Klaver B., Krone W., Tersmette M., de Ronde A. Human immunodeficiency virus type 1 clones chimeric for the envelope V3 domain differ in syncytium formation and replication capacity. J Virol. 1992 Feb;66(2):757–765. doi: 10.1128/jvi.66.2.757-765.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. de Ronde A., Stam J. G., Boers P., Langedijk H., Meloen R., Hesselink W., Keldermans L. C., van Vliet A., Verschoor E. J., Horzinek M. C. Antibody response in cats to the envelope proteins of feline immunodeficiency virus: identification of an immunodominant neutralization domain. Virology. 1994 Jan;198(1):257–264. doi: 10.1006/viro.1994.1028. [DOI] [PubMed] [Google Scholar]

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