Efficient HIV-1 replication can occur in the absence of the viral matrix protein.

Autor: Reil, Heide, Bukovsky, Anatoly A., Gelderblom, Hans R., Göttlinger, Heinrich G.
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Zdroj: EMBO Journal; 5/1/98, Vol. 17 Issue 9, p2699-2708, 10p
Abstrakt: 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 import of the viral genome in non-dividing cells. We now show that the entire MA protein is dispensable for the incorporation of HIV-1 Env glycoproteins 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. Additional compensatory changes in Gag permitted efficient virus replication even if all of MA was replaced by a heterologous membrane targeting 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 particles that lacked the structurally conserved globular head ofMAefficiently infected macrophages, indicating that MA is dispensable for nuclear import in terminally differentiated cells. [ABSTRACT FROM AUTHOR]
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