Extended nucleocapsid protein is cleaved from the Gag-Pol precursor of human immunodeficiency virus type 1.

Experimental Pathology Unit and Clinical Virology Unit, The Hebrew University, Hadassah Medical School, PO Box 12272, Jerusalem 91120, Israel.

Human immunodeficiency virus type 1 Gag and Gag-Pol precursors are translated from an mRNA which is indistinguishable from the full-length genomic RNA. The ratio of Gag to Gag-Pol polyproteins is approximately 20:1 and is controlled by a frameshift of the reading frame, which takes place downstream of the p7 nucleocapsid (NC) in the N terminus of the p1 peptide. The viral precursors Gag and Gag-Pol are cleaved by the virus-encoded protease (PR) into the structural proteins, and into p6(Pol), PR, reverse transcriptase and integrase. Due to the frameshift event, the cleavage site at the C terminus of NC coded in the Gag frame (ERQAN-FLGKI) changes either to ERQANFLRED or ERQANFFRED. The results presented in this report demonstrate that the NC released from the Gag-Pol precursor is 8 amino acid residues longer than the NC cleaved from the Gag polyprotein. Our results also show that truncated Gag-Pol precursors bearing cleavage site mutation at the NC/p6(Pol), and/or p6(Pol)/PR junctions, undergo autoprocessing in bacterial and eukaryotic cells, indicating that PR is active when part of the precursor.

PMID: 11172099 [PubMed - indexed for MEDLINE]