Processing and secretion of envelope glycoproteins of human immunodeficiency virus type 1 in the presence of trimming glucosidase inhibitor deoxynojirimycin.
The processing and secretion of the envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) were studied in chronically infected cells treated with the trimming glucosidase inhibitor deoxynojirimycin (DNM). In Molt3 cells infected with human T-lymphotropic virus type III (HTLV-IIIB), DNM inhibited the intracellular proteolytic processing of gp160 to gp120 and gp41. A clone of the HUT78 cell line called 6D5, when chronically infected with the HIV-1 isolate HTLV-III451 was shown to release both gp160 and gp120 into the culture medium. The secretion of envelope glycoproteins from these infected cells was not inhibited by DNM treatment. The secreted proteins had higher molecular weights than gp160 and gp120 from cultures not treated with DNM, presumably due to the presence of unprocessed carbohydrate residues on the polypeptide chain. These secreted glycoproteins from DNM-treated cells exhibited specific interaction with the CD4 molecule on the surface of target cells. However, the syncytium formation induced by HIV-1-infected cells on CD4+ cells was significantly inhibited in the presence of the glucosidase inhibitor. The minimal cytotoxicity of the DNM coupled with its strong inhibitory effect on the cell-to-cell spread of the virus suggest that it may be potentially useful in antiviral drug therapy of HIV-1 infection.
Pal
R
R
Department of Cell Biology, Bionetics Research Inc., Rockville, Md 20850.
Kalyanaraman
V S
VS
Hoke
G M
GM
Sarngadharan
M G
MG
D017485:1-Deoxynojirimycin; D002459:Cell Fusion; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D005944:Glucosamine / Q000031:analogs & derivatives / Q000494:pharmacology; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012191:Retroviridae Proteins / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000378:metabolism*
D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D012191:Retroviridae Proteins; D014759:Viral Envelope Proteins; D017485:1-Deoxynojirimycin; D005944:Glucosamine