ROLE OF THE C-TERMINUS GAG PROTEIN IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 VIRION ASSEMBLY AND MATURATION

Lentiviral Gag polyproteins have a proline-rich protein, p6, at their C terminus. There are conflicting reports about the function of p6 in virus release. In the present work, mutants that affect p6 of human im munodeficiency virus type 1 (HIV-1) Gag polyprotein were constructed a nd analysed. None of the mutants prevented virus release completely; h owever, detachment of budding particles was less efficient as evidence d by electron microscopy. Virions of the p6 truncation mutant B2TAA ha d a significantly reduced number of Pol proteins (p66, p51 and p34) an d an increased amount of incompletely processed Gag proteins compared with the parental virus. A mutation that altered the cleavage site bet ween p6 and p1 did not significantly affect virus assembly, virus rele ase or protein processing with the exception of cleavage between p6 an d p1. However, virions of this mutant (B2P6C) exhibited irregular-shap ed core structures that were distinct from the con-shaped core structu re seen in the parental virion. B2P6C mutant virus was non-infectious in CD4(+) T cells. These results suggest that mutations in p6 affect e fficient detachment of budding particles from the cell surface. Proper cleavage between p6 and p1 may be critical for the formation of the d istinctive cone-shaped core structure of HIV-1 virions.