TY - JOUR
T1 - Inhibition of HIV and SIV infectivity by blockade of α-glucosidase activity
AU - Ratner, Lee
AU - Heyden, Nancy Vander
AU - Dedera, Douglas
N1 - Funding Information:
We thank T. Braciale and C. Rice for the gifts of the vaccinia expression clone, wild-type vacclnla virus, and CVl cells, and advice on the experimental methodology, S. Gartner for HIV-1 strain BaL. H. Gendelman for advice on macrophage cultures, M. Hanamoto (Cetus) for M-CSF, R. Brown for elutriated macrophages, A. Cantor for advice on the endoglycosidase H experiments, S. and R. Kornfeld for advice and encouragement In these studies as well as the BW5 147 and PHAR2.’ cell lines, D. Tiemeier and R. Mueller for the gift of N-BuDNJ (SC-48334), R. Desrosiers for the gift of SlVmac antisera, M. Arens for the HIV-l antisera (collected with support from Al25903, Washington University AIDS ClInIcal Trials Unit), and NIAID AIDS Repository for SlVmac186-Infected H9 cells. This work was supported by NIH Grants Al24745 and Al27302, and a Washington Unl-versity Searle/Monsanto Corporation Research Agreement. L.R. is an American Cancer Society Research Professor.
PY - 1991/3
Y1 - 1991/3
N2 - Processing of HIV and SIV envelope oligosaccharides is critical for proper intracellular trafficking and function. An inhibitor of α-glucosidases I and 11, N-butyl deoxynojirimycin (N-BuDNJ), retards HIV-1 and SIVmac spread in lymphocytes and monocytes by diminishing virus infectivity, and also causes a reduction in syncytia formation between infected cells and uninfected lymphocytes. N-BuDNJ retards envelope processing from the precursor form to the mature surface (SU) and transmembrane proteins in HIV-1- and SIVmac-infected cells, as well as in cells infected with vaccinia-HIV-1 envelope recombinant virus. However, no significant reduction is seen in the amount of SU in released virus particles, though the virus particle-associated SU from N-BuDNJ-treated cells has an altered electrophoretic mobility. In contrast, N-BuDNJ had no effect on GAG protein synthesis and processing. These findings demonstrate a critical requirement for oligosaccharide processing by α-glucosidases I and It for HIV-1 and SIVmac envelope processing and fusogenicity.
AB - Processing of HIV and SIV envelope oligosaccharides is critical for proper intracellular trafficking and function. An inhibitor of α-glucosidases I and 11, N-butyl deoxynojirimycin (N-BuDNJ), retards HIV-1 and SIVmac spread in lymphocytes and monocytes by diminishing virus infectivity, and also causes a reduction in syncytia formation between infected cells and uninfected lymphocytes. N-BuDNJ retards envelope processing from the precursor form to the mature surface (SU) and transmembrane proteins in HIV-1- and SIVmac-infected cells, as well as in cells infected with vaccinia-HIV-1 envelope recombinant virus. However, no significant reduction is seen in the amount of SU in released virus particles, though the virus particle-associated SU from N-BuDNJ-treated cells has an altered electrophoretic mobility. In contrast, N-BuDNJ had no effect on GAG protein synthesis and processing. These findings demonstrate a critical requirement for oligosaccharide processing by α-glucosidases I and It for HIV-1 and SIVmac envelope processing and fusogenicity.
UR - https://www.scopus.com/pages/publications/0026064060
U2 - 10.1016/0042-6822(91)90483-R
DO - 10.1016/0042-6822(91)90483-R
M3 - Article
C2 - 1704656
AN - SCOPUS:0026064060
SN - 0042-6822
VL - 181
SP - 180
EP - 192
JO - Virology
JF - Virology
IS - 1
ER -