Processing of the structural proteins of human immunodeficiency virus type 1 in the presence of monensin and cerulenin.
The synthesis and processing of structural proteins of human immunodeficiency virus type 1 (HIV-1) were studied in infected cells treated with monensin and cerulenin. In MOLT-3 cells chronically infected with HTLV-IIIB, monensin inhibited the proteolytic cleavage of the env-coded polyprotein gp160 to gp120, leading to the accumulation of the precursor gp160. The formation of syncytia normally observed when CEM cells are cocultivated with HIV-1-infected MOLT-3 cells was significantly inhibited in the presence of monensin. The effect of the ionophore on the culture was reversible, as withdrawal of monensin from the medium restored the ability of the cells to form syncytia with CEM cells and led to the resumption of the processing of gp160 to gp120. Monensin did not affect the synthesis and processing of gag-coded proteins and regulatory proteins. Cerulenin, an inhibitor of de novo fatty acid biosynthesis, inhibited the myristoylation and the proteolytic cleavage of the gag-coded polyprotein Pr53gag to p24 but did not affect the processing of gp160. However, use for monensin and cerulenin as antiviral agents for treatment of HIV-1 infection cannot be foreseen because of the pronounced in vitro toxicity observed.
Pal
R
R
Department of Cell Biology, Bionetics Research, Inc., Rockville, MD 20850.
Gallo
R C
RC
Sarngadharan
M G
MG
D000935:Antifungal Agents / Q000494:pharmacology*; D002460:Cell Line; D002569:Cerulenin / Q000494:pharmacology*; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008715:Methionine / Q000378:metabolism; D008985:Monensin / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational; D014764:Viral Proteins / Q000096:biosynthesis* / Q000235:genetics
D000935:Antifungal Agents; D006023:Glycoproteins; D014764:Viral Proteins; D002569:Cerulenin; D008985:Monensin; D008715:Methionine