Cleavage of p15 protein in vitro by human immunodeficiency virus type 1 protease is RNA dependent.

AUTOR(ES)

Sheng, N

RESUMO

The human immunodeficiency virus (HIV) gag polyprotein is processed by the viral protease to yield the structural proteins of the virus. One of these structural proteins, p15, and its protease cleavage products, p7 and p6, are believed to be responsible for the viral RNA binding which is prerequisite for assembly of infectious virions. To better understand potential interactions between viral RNA, p15, and the HIV protease, we have synthesized p15 in an in vitro system and studied its processing by the viral protease. Using this system, we demonstrate that p15 synthesized in vitro is properly cleaved by the HIV protease in an RNA-dependent reaction. Mutation of cysteine residues in either zinc-binding domain of the p7 portion of p15 does not alter the RNA-dependent cleavage, but mutation of three basic residues located between the zinc-binding domains blocks HIV protease susceptibility. The results support a previously unrecognized role for the interaction of RNA and nucleocapsid-containing gag precursors that may have important consequences for virus assembly.

Documentos Relacionados

• Determinants of the human immunodeficiency virus type 1 p15NC-RNA interaction that affect enhanced cleavage by the viral protease.
• In vitro transcription of human T-cell leukemia virus type 1 is RNA polymerase II dependent.
• Infection of brain microglial cells by human immunodeficiency virus type 1 is CD4 dependent.
• Topoisomerase II cleavage of herpes simplex virus type 1 DNA in vivo is replication dependent.
• The p15 carboxyl-terminal proteolysis product of the human immunodeficiency virus type 1 reverse transcriptase p66 has DNA polymerase activity.