VIF IS CRUCIAL FOR HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 PROVIRAL DNA-SYNTHESIS IN INFECTED-CELLS

The human immunodeficiency virus type 1 (HIV-1) vif gene encodes a 23- kDa protein of unknown function, also produced by most other known len tiviruses. Vif was found to be essential for the spread of HIV-1 in pe ripheral blood lymphocytes and in primary macrophages, as well as in s ome but not all established T-cell lines. Vif was required at the stag e of viral particle formation, for cell-to-cell as well as for cell-fr ee transmission of HIV-1. Accordingly, vif-defective viruses could be complemented by the expression of vif in the producer but not in the t arget cell. vif-defective virions contained wild-type amounts of Gag a nd Env proteins, reverse transcriptase, integrase, genomic RNA, and pa rtial reverse transcripts. Most importantly, they could enter cells no rmally, 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 sugg est that Vif plays a role which is novel for a retroviral protein, in allowing the processing and/or the transport of the internalized HIV c ore.