Brefeldin A inhibits the processing and secretion of envelope glycoproteins of human immunodeficiency virus type 1.
The processing and secretion of the envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) were studied in chronically infected T cells and in primary macrophages treated with an antiviral antibiotic brefeldin A (BFA). BFA blocks the egress of proteins from the endoplasmic reticulum and has a profound effect on the structure of cis/medial Golgi. In MOLT-3 cells infected with the IIIB strain of HIV-1 (MOLT-3/IIIB), BFA inhibited the intracellular processing of gp160. The secretion of envelope proteins from these cells was significantly inhibited in the presence of BFA. The gag proteins, on the other hand, were processed and secreted normally. BFA also inhibited the proteolytic processing of gp160 in primary macrophages infected with HIV-1. The infectivity of virus pelleted from the medium of MOLT-3/IIIB cells treated with BFA was markedly lower than that obtained from untreated cells. These results demonstrate that the proteolytic processing of gp160 in HIV-1-infected cells takes place after the glycoprotein exists the endoplasmic reticulum and that the transport of glycoprotein to the cell surface is required for assembly of complete HIV-1 particles.
Pal
R
R
Department of Cell Biology, Advanced BioScience Laboratories, Kensington, MD 20895.
Mumbauer
S
S
Hoke
G M
GM
Takatsuki
A
A
Sarngadharan
M G
MG
D000998:Antiviral Agents / Q000494:pharmacology*; D020126:Brefeldin A; D002240:Carbohydrate Sequence; D002458:Cell Fractionation; D002460:Cell Line; D003517:Cyclopentanes / Q000494:pharmacology*; D015686:Gene Products, env / Q000187:drug effects* / Q000378:metabolism; D019302:HIV Envelope Protein gp160; D054303:HIV Reverse Transcriptase; D006679:HIV Seropositivity / Q000382:microbiology; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism / Q000472:pathogenicity; D006801:Humans; D008264:Macrophages / Q000382:microbiology; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D011498:Protein Precursors / Q000187:drug effects* / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism
D000998:Antiviral Agents; D003517:Cyclopentanes; D015686:Gene Products, env; D019302:HIV Envelope Protein gp160; D011498:Protein Precursors; D020126:Brefeldin A; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase