Enhanced proteolytic processing of the human immunodeficiency virus type 1 envelope protein in murine Ltk(-) cells.
Proteolytic processing of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) precursor glycoprotein (gp160) to produce the mature gp120 and gp41 proteins is required for virus infection and virus-induced cell fusion. It has also been suggested that cleavage of gp120 at the immunodominant V3 loop region is required for virus-to-cell and cell-to-cell fusion. In this investigation we have studied the proteolytic processing of the HIV-1 Env in cells of various origins (human, monkey, and mouse) infected with a vaccinia virus recombinant expressing the entire gp160 protein (VV-env-1). We have observed that in murine Ltk(-) cells, in addition to the proteolytic cleavage of gp160 at the gp120/gp41 site, there is also extensive intracellular proteolytic processing of gp160 at the V3 loop and at a novel site located at the C terminus of gp41. Similar proteolytic processing of the Env precursor was observed after treatment of extracts of VV-env-1-infected monkey cells with thrombin, a trypsin-like protease that has been shown to cleave the gp120 at the V3 loop. Our findings suggest that murine Ltk(-) cells could be a good model system for structural studies of Env with different HIV isolates and in searches for proteinase inhibitors that could prevent HIV-1 infection of susceptible cells by blocking proteolysis of Env.
Rodriguez
D
D
Centro Nacional de Biotecnología, CSIC, Campus Universidad Autónoma, Madrid, Spain.
Rodriguez
J R
JR
Esteban
M
M
D000818:Animals; D002460:Cell Line; D015686:Gene Products, env / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41 / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D000882:Haplorhini; D006801:Humans; D051379:Mice; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis; D013917:Thrombin / Q000494:pharmacology
D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41; D011498:Protein Precursors; D011994:Recombinant Proteins; D013917:Thrombin