ROLE OF LXXLF VPR-BINDING MOTIF OF P6ᴳᴬᴳ PROTEIN IN HIV-1 REPLICATION

Abstract

Conserved sequence motifs are generally linked to crucial biological functions. Yet, the highly conserved LXXLF motif of HIV-1 p6ᴳᵃᵍ has not been found essential for HIV-1 replication in T lymphocytes. To determine a possible role of LXXLF motif in HIV-1 replication cycle, we evaluated the effect of LXXLF-to-PXXPS mutation on virion production and infectivity. 293T cells transfected with PXXPS plasmid released fewer and less infectious virion particles. Electron microscopy analysis demonstrated mostly immature, tear-drop shaped virion particles being released from the PXXPS- transfected cells. Western blot analysis of LXXLF-mutant virion particles revealed reduced incorporation of envelope protein. Furthermore, the LXXLF-mutant virus failed to replicate in the majority of T cell lines and normal donor PBMC employed, after proviral integration into host cell DNA was established. These data suggest that LXXLF motif may be critically involved in virion assembly process and Env incorporation into maturing virions.