This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gemeniano, M. C. Articles by Sparger, E. E. Search for Related Content PubMed PubMed Citation Articles by Gemeniano, M. C. Articles by Sparger, E. E.

Feline Immunodeficiency Virus Orf-A Is Required for Virus Particle Formation and Virus Infectivity

Department of Medicine and Epidemiology, School of Veterinary Medicine,¹ Department of Medical Pathology, School of Medicine, University of California, Davis, California 95616²

Received 30 January 2003/ Accepted 15 May 2003

The orf-A (orf-2) gene of feline immunodeficiency virus (FIV) is a small open reading frame predicted to encode a 77-amino-acid protein that contains putative domains similar to those of the ungulate lentiviral Tat protein. Orf-A is reported to be critical for efficient viral replication in vitro and in vivo. A series of FIV-pPPR-derived proviruses with in-frame deletions and point mutations within orf-A were constructed and tested for replication in feline lymphoid cells. Orf-A mutant proviruses were also tested for viral gene and protein expression, viral particle formation, and virion infectivity. Deletions within orf-A severely restricted FIV replication in feline peripheral blood mononuclear cells (PBMC) and interleukin-2-dependent T-cell lines. In addition, substitutions of alanines for leucines in the putative leucine-rich domain, for cysteines in the putative cysteine-rich domain, and for a tryptophan at position 43 in Orf-A restricted the replication of FIV mutants. Deletions and point mutations in orf-A imposed a small effect or no effect on FIV long-terminal-repeat-driven viral gene expression and had no effect on viral protein expression. However, release of cell-free, virion-associated viral RNA in supernatants from cells transfected with orf-A mutant proviruses was severely restricted but was rescued by cotransfection with a wild-type Orf-A expression vector. In addition, virions derived from orf-A mutant proviruses expressed reduced infectivity for feline PBMC. Our findings suggest that Orf-A functions involve multiple steps of the FIV life cycle including both virion formation and infectivity. Furthermore, these observations suggest that Orf-A represents an FIV-encoded analog more similar to the accessory gene vpr, vpu, or nef than to the regulatory gene tat encoded by the primate lentiviruses.

This article has been cited by other articles:

• James, L., Sargueil, B. (2008). RNA secondary structure of the feline immunodeficiency virus 5'UTR and Gag coding region. Nucleic Acids Res 0: gkn447v1-gkn447 [Abstract] [Full Text]  
• Gupta, S., Leutenegger, C. M., Dean, G. A., Steckbeck, J. D., Cole, K. S., Sparger, E. E. (2007). Vaccination of Cats with Attenuated Feline Immunodeficiency Virus Proviral DNA Vaccine Expressing Gamma Interferon. J. Virol. 81: 465-473 [Abstract] [Full Text]  
• van der Meer, F. J. U. M., Schuurman, N. M. P., Egberink, H. F. (2007). Feline immunodeficiency virus infection is enhanced by feline bone marrow-derived dendritic cells. J. Gen. Virol. 88: 251-258 [Abstract] [Full Text]  
• VandeWoude, S., Apetrei, C. (2006). Going Wild: Lessons from Naturally Occurring T-Lymphotropic Lentiviruses. Clin. Microbiol. Rev. 19: 728-762 [Abstract] [Full Text]  
• Pistello, M., Bonci, F., Flynn, J. N., Mazzetti, P., Isola, P., Zabogli, E., Camerini, V., Matteucci, D., Freer, G., Pelosi, P., Bendinelli, M. (2006). AIDS Vaccination Studies with an Ex Vivo Feline Immunodeficiency Virus Model: Analysis of the Accessory ORF-A Protein and DNA as Protective Immunogens.. J. Virol. 80: 8856-8868 [Abstract] [Full Text]