INFLUENCE OF MA INTERNAL SEQUENCES, BUT NOT OF THE MYRISTYLATED N-TERMINUS SEQUENCE, ON THE BUDDING SITE OF HIV-1 GAG PROTEIN

HIV-1 Gag protein intracellular transport and budding was investigated by altering the sequence of the MA domain, which directly bears an es sential N-terminal myristyl adduct and forms the viral matrix after Ga g proteolysis in mature virions. We found that removal of a substantia l MA internal segment did not abolish the assembly and budding of Gag particles, but rather diverted these events to intracellular cisternae . The internally deleted Gag was further modified by substituting eith er of two heterologous myristylated N-termini for the natural one: ami no acids 1-12 from v-Src oncoprotein (for which a membrane-bound intra cellular receptor has been postulated), or amino acids 1-12 from Polio virus polyprotein (for which no membrane-targeting function has been d emonstrated). Both Src-Gag and Polio-Gag chimerae exhibited transport and processing characteristics similar to those of the MA-deleted Gag. These results are discussed with respect to the possible transport pa thway of HIV-1 Gag. (C) 1994 Academic Press, Inc.