Role of oligosaccharides in the processing and maturation of envelope glycoproteins of human immunodeficiency virus type 1.
The processing and maturation of envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) were studied in infected cells treated with inhibitors of oligosaccharide processing. In MOLT-3 cells chronically infected with HIV-1 (strain HTLV-IIIB), tunicamycin severely inhibited the glycosylation of envelope proteins. Deoxynojirimycin, an inhibitor of glucosidase I in the rough endoplasmic reticulum, inhibited the proteolytic processing of gp160, whereas no such effect was noted with either deoxymannojirimycin or swainsonine, inhibitors of mannosidase I and II, respectively, in the Golgi complex. The processed gp120 and gp41 synthesized in the presence of deoxymannojirimycin were found to contain mannose-rich oligosaccharide cores as evidenced by their susceptibility to endoglycosidase H digestion. The formation of syncytia normally observed when CEM cells are cocultured with HIV-1-infected cells was markedly inhibited in the presence of deoxynojirimycin, but such inhibition was not observed in cells treated with deoxymannojirimycin or swainsonine. The infectivity of virions released from MOLT-3/HTLV-IIIB cells treated with deoxynojirimycin or deoxymannojirimycin was significantly lower than the infectivity of virions released from untreated cells. On the other hand, treatment with swainsonine did not affect the infectivity of the progeny virus. These results suggest that the proteolytic processing of gp160 takes place in infected cells when the glycoprotein has mannose-rich oligosaccharide structures. Trimming of glucose residues and the primary trimming of mannose residues are necessary for the release of infectious virus.
Pal
R
R
Department of Cell Biology, Bionetics Research, Inc., Kensington, MD 20895.
Hoke
G M
GM
Sarngadharan
M G
MG
D017485:1-Deoxynojirimycin; D000470:Alkaloids / Q000494:pharmacology; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D005944:Glucosamine / Q000031:analogs & derivatives / Q000494:pharmacology; D006023:Glycoproteins / Q000378:metabolism*; D065089:Glycoside Hydrolase Inhibitors; D006031:Glycosylation; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism; D015488:HIV Antigens / Q000378:metabolism; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41; D015497:HIV-1 / Q000378:metabolism* / Q000472:pathogenicity; D008358:Mannose / Q000378:metabolism; D008361:Mannosidases / Q000037:antagonists & inhibitors; D009844:Oligosaccharides / Q000378:metabolism*; D012191:Retroviridae Proteins / Q000378:metabolism; D017026:Swainsonine; D014415:Tunicamycin / Q000494:pharmacology; D014759:Viral Envelope Proteins / Q000378:metabolism*; D000520:alpha-Glucosidases
D000470:Alkaloids; D006023:Glycoproteins; D065089:Glycoside Hydrolase Inhibitors; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41; D009844:Oligosaccharides; D012191:Retroviridae Proteins; D014759:Viral Envelope Proteins; D014415:Tunicamycin; D017485:1-Deoxynojirimycin; D008361:Mannosidases; C042059:glucosidase I; D000520:alpha-Glucosidases; D005944:Glucosamine; D008358:Mannose; D017026:Swainsonine