Genetic evidence for an interaction between human immunodeficiency virus type 1 matrix and alpha-helix 2 of the gp41 cytoplasmic tail

The incorporation of envelope (Env) glycoproteins into virions is an essent ial step in the retroviral replication cycle. Lentiviruses, including human immunodeficiency virus type 1 (HTV-1), encode Env glycoproteins with unusu ally long cytoplasmic tails, the functions of which have not been fully elu cidated. In this study, we examine the effects on virus replication of a nu mber of mutations in a helical motif (alpha-helix 2) located near the cente r of the HIV-1 gp41 cytoplasmic tail. We find that, in T-cell lines, small deletions in this domain disrupt the incorporation of Env glycoproteins int o virions and markedly impair virus infectivity. Through the analysis of vi ral revertants, we demonstrate that a single amino acid change (34VI) in th e matrix domain of Gag reverses the Env incorporation and infectivity defec t imposed by a small deletion near the C terminus of a-helix 2. These resul ts provide genetic evidence, in the context of infected T cells, for an int eraction between HIV-1 matrix and the gp41 cytoplasmic tail and identify do mains of both proteins involved in this putative interaction.