A sequence related to the human gonadoliberin precursor near the N-termini of HIV and SIV gag polyproteins

Abstract

A highly conserved sequence near the N-terminus of all human (HIV) and simian (SIV) immunodeficiency virus gag polyproteins appears to be a precursor for a viral mimic of the amidated C-terminus of human gonadoliberin. The gag polyproteins are known to be myristylated; processing of the amidation site would yield myristylated 23-residue peptides whose C-terminal sequences mimic gonadoliberin and presumably behave as ligands for the gonadoliberin receptor. This paper describes the discovery of conserved gonadoliberin-precursor-related sequences in HIV and SIV gag polyproteins and in the p-17 core proteins derived from them. Arguments are presented that the conserved precursor structure requires post-translational processing to a peptide amide derivative which is a ligand for the gonadoliberin receptor. A model has been developed for entry of the viral genomic RNA into host cells through the gonadoliberin receptor and experiments are suggested to confirm or refute the model. This proposed mechanism for entry of HIV genomic RNA into host cells, if it proves to be substantially correct, suggests several new approaches to prevention and treatment of acquired immunodeficiency syndrome (AIDS).