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Comprehensive Investigation of the Molecular Defect in vif-Deficient Human Immunodeficiency Virus Type 1 Virions

Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104,¹ AIDS Vaccine Program, SAIC Frederick, National Cancer Institute at Frederick, Frederick, Maryland 21702,² Department of Infectious Diseases, Guy's, King's, and St. Thomas' School of Medicine, King's College London, London SE1 9RT, United Kingdom³

Received 18 November 2002/ Accepted 11 February 2003

Replication of human immunodeficiency virus type 1 (HIV-1) in primary blood lymphocytes, certain T-cell lines (nonpermissive cells), and most likely in vivo is highly dependent on the virally encoded Vif protein. Evidence suggests that Vif acts late in the viral life cycle during assembly, budding, and/or maturation to counteract the antiviral activity of the CEM15 protein and possibly other antiviral factors. Because HIV-1 virions produced in the absence of Vif are severely restricted at a postentry, preintegration step of infection, it is presumed that such virions differ from wild-type virions in some way. In the present study, we established a protocol for producing large quantities of vif-deficient HIV-1 (HIV-1/vif) from an acute infection of nonpermissive T cells and performed a thorough examination of the defect in these virions. Aside from the expected lack of Vif, we observed no apparent abnormalities in the packaging, modification, processing, or function of proteins in vif virions. In addition, we found no consistent defect in the ability of vif virions to perform intravirion reverse transcription under a variety of assay conditions, suggesting that the reverse transcription complexes in these particles can behave normally under cell-free conditions. Consistent with this finding, neither the placement of the primer tRNA3Lys nor its ability to promote reverse transcription in an in vitro assay was affected by a lack of Vif. Based on the inability of this comprehensive analysis to uncover molecular defects in vif virions, we speculate that such defects are likely to be subtle and/or rare.

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