EFFICIENT HIV-1 REPLICATION CAN OCCUR IN THE ABSENCE OF THE VIRAL MATRIX PROTEIN

Matrix (MA), a major structural protein of retroviruses, is thought to play a critical role in several steps of the HIV-1 replication cycle, including the plasma membrane targeting of Gag, the incorporation of envelope (Env) glycoproteins into nascent particles, and the nuclear i mport of the viral genome in nondividing cells. We now show that the e ntire MA protein is dispensable for the incorporation of HIV-1 Env gly coproteins with a shortened cytoplasmic domain. Furthermore, efficient HIV-1 replication in the absence of up to 90% of MA was observed in a cell line in which the cytoplasmic domain of Env is not required. Add itional compensatory changes in Gag permitted efficient virus replicat ion even if all of MA was replaced by a heterologous membrane targetin g signal. Viruses which lacked the globular domain of MA but retained its N-terminal myristyl anchor exhibited an increased ability to form both extracellular and intracellular virus particles, consistent with a myristyl switch model of Gag membrane targeting. Pseudotyped HIV-1 p articles that lacked the structurally conserved globular head of MA ef ficiently infected macrophages, indicating that MA is dispensable for nuclear import in terminally differentiated cells.