HIV-1 infection abolishes CD4 biosynthesis but not CD4 mRNA.
In order to improve understanding of how HIV-1 infection down-modulates cell surface membrane expression of CD4, we have measured several parameters of CD4 expression in the human tumor T-cell lines CEM and MOLT-4 at different times after infection. Three independent HIV-1 isolates were used including one that encodes a truncated nef protein and another that appeared to be noncytolytic against CEM. The level of CD4 mRNA, the rate of biosynthesis of CD4 protein, and the percentage of CD4-positive cells were measured. With each viral isolate it was found that infection led to a specific and almost complete inhibition of CD4 protein biosynthesis. This substantially exceeded, at every time point after infection, a concomitant reduction in CD4 mRNA. Hence an inhibition of translation probably accounts for much of the decline in the rate of CD4 biosynthesis. This implicates a novel selective translational inhibition of host gene expression by HIV-1 as a factor in the disappearance of surface membrane CD4 from infected cultures.
Yuille
M A
MA
Department of Microbiology and Immunology, State University of New York Health Science Center, Syracuse 13210.
Hugunin
M
M
John
P
P
Peer
L
L
Sacks
L V
LV
Poiesz
B J
BJ
Tomar
R H
RH
Silverstone
A E
AE
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis* / Q000235:genetics; D015152:Blotting, Northern; D015497:HIV-1; D006801:Humans; D012333:RNA, Messenger / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D012333:RNA, Messenger