The role and fate of the CD4 molecule in lymphocytes and monocytes infected by HIV-1.
Infection by HIV-1 of monocyte cell lines, in contrast to T lymphocytes, did not lead to decreased steady-state levels of CD4 mRNA. Similar results were also obtained using clonal derivatives of infected U-937 cells that produced either competent, highly replicative progeny viruses or defective non-infectious particles. In each case, the infected U-937 cells or clonal derivatives were found to be significantly deficient with regard to surface representation of CD4 protein, in spite of the presence of high levels of CD4 mRNA. However, both HIV-1-infected U-937 cells, as well as clonal derivatives which produced high levels of viral env mRNA and non-infectious viral structures that lacked envelope glycoproteins, contained diminished levels of OKT4-immunoprecipitable CD4 protein, in comparison with uninfected U-937 cells. Thus, expression of viral env mRNA but neither the efficient synthesis or packaging of viral glycoproteins or viral assembly is required for disappearance of cell surface CD4 to occur. Furthermore, viral gp160 co-precipitated with CD4 in both the parental and cloned cell lines. We have also shown that the generation of intracellular complexes of gp160 and CD4 is directly responsible for the disappearance of cell surface CD4 in HIV-1-infected U-937 cells. In this system, expression of gp160 was both necessary and sufficient to result in CD4 receptor down-modulation. Finally, in vitro co-translation studies revealed that the presence or synthesis of viral gp160 led to a failure to efficiently generate CD4 protein.
Wainberg
M A
MA
McGill AIDS Centre, Montreal, Canada.
Geleziunas
R
R
Bour
S
S
D015152:Blotting, Northern; D015704:CD4 Antigens / Q000032:analysis / Q000502:physiology*; D002460:Cell Line; D005434:Flow Cytometry; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000032:analysis; D012194:RNA-Directed DNA Polymerase / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
D015704:CD4 Antigens; D012333:RNA, Messenger; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase