Vif is crucial for human immunodeficiency virus type 1 proviral DNA synthesis in infected cells

Abstract

The human immunodeficiency virus type 1 (HIV-1) vif gene encodes a 23-kDa protein of unknown function, also produced by most other known lentiviruses. Vif was found to be essential for the spread of HIV-1 in peripheral blood lymphocytes and in primary macrophages, as well as in some but not all established T-cell lines. Vif was required at the stage of viral particle formation, for cell-to-cell as well as for cell-free transmission of HIV-1. Accordingly, vif-defective viruses could be complemented by the expression of vif in the producer but not in the target cell. vif-defective virions contained wild-type amounts of Gag and Env proteins, reverse transcriptase, integrase, genomic RNA, and partial reverse transcripts. Most importantly, they could enter cells normally, and the vif defect could not be rescued through the use of HIV(MLV [murine leukemia virus]) pseudotypes. Instead, vif-mutant viruses were severely impaired in their ability to complete the synthesis of proviral DNA, once internalized in the target cell. These results suggest that Vif plays a role which is novel for a retroviral protein, in allowing the processing and/or the transport of the internalized HIV core.