HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 VIF(-) MUTANT PARTICLES FROM RESTRICTIVE CELLS - ROLE OF VIF IN CORRECT PARTICLE ASSEMBLY AND INFECTIVITY

Disruption of the vif gene of human immunodeficiency virus (HIV) type 1 affects virus infectivity to various degrees, depending on the T-cel l line used. We have concentrated our studies on true phenotypic Vif(- ) mutant particles produced from CEMx174 or H9 cells. In a single roun d of infection, Vif(-) virus is approximately 25 (from CEMx174 cells) to 100 (from H9 cells) times less infectious than wild-type virus prod uced from these cells or than the Vif(-) mutant produced from HeLa cel ls. Vif(-) virions recovered from restrictive cells, but not from perm issive cells, are abnormal both in terms of morphology and viral prote in content. Notably, they contain much reduced quantities of envelope proteins and altered quantities of Gag and Pol proteins. Although wild -type and Vif(-) virions from restrictive cells contain similar quanti ties of viral RNA, no viral DNA synthesis was detectable after acute i nfection of target cells with phenotypically Vif(-) virions. To examin e the possible role of Vif(-) in viral entry, attempts were made to re scue the Vif(-) defect in H9 cells by pseudotyping Vif(+) and Vif(-) H IV particles with amphotropic murine leukemia virus envelope. Vif(-) p articles produced in the presence of HIV envelope could not be propaga ted when pseudotyped. In contrast, when only the murine leukemia virus envelope was present, significant propagation of Vif(-) HIV particles could be detected. These results demonstrate that Vif is required for proper assembly of the viral particle and for efficient HIV Env-media ted infection of target cells.