COMPARATIVE ANALYSES OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1) AND HIV-2 VIF MUTANTS

Virion infectivity factor (vif), a gene found in all lentiviruses, plays an essential role in virus replication in certain target cells. We examined the replication competence of the human immunodeficiency virus type 2 (HIV-2) vif mutant in different T-cell lines and primary cells in comparison with that of the HIV-1 vif mutant. Both mutant viruses were unable to replicate in peripheral blood derived mononuclear cells but replicated with wild-type efficiency in certain T-cell lines, such as SupT1 and MOLT-4/8. These results confirm the importance of vif in the infection of relevant target cells and imply that some cellular factor(s) could compensate for vif function. However, HIV-1 and HIV-2 vif mutant viruses also show differential replications in other cell lines, suggesting either different threshold requirements for the same cellular factor(s) or the involvement of different factors to compensate for vif-1 and vif-2 functions. By cross complementation experiments, we showed that vif-1 and vif-2 have similar functions. Our studies further indicate the existence of two kinds of nonpermissive cells: H9 is unable to complement HIV-1(Delta vif) but is susceptible to a one-round infection with HIV-1(Delta vif) produced from permissive cells. In contrast, U937 is nonpermissive for HIV-2(Delta vif) produced from permissive cells but, once infected, is able to complement the Delta vif function. In both types of nonpermissive cells, a step prior to proviral DNA synthesis is affected.