HIV-1 transmission and function of virus-infected monocytes/macrophages.
Monocyte/macrophages (MM) were isolated from HIV-1 seronegative individuals, infected with HIV-1 and examined for their ability to infect autologous T lymphocytes with and without concomitant presentation of exogenous Ag. HIV-1-infected MM presented tetanus toxin (TT) and streptokinase to T cells (as measured by [3H]thymidine incorporation) comparable to presentation by uninfected MM. In these studies, it was observed that HIV-1-infected MM without additional exogenous Ag stimulated autologous T lymphocytes, however, to a lesser degree than with TT and streptokinase. Virus production in T cells appeared to be relative to the degree of stimulation with the highest levels of stimulation and infection observed when T cells were exposed to HIV-1-infected TT-presenting MM. Studies were carried out to examine some of the restricting elements in MM-mediated infection of T lymphocytes with and without TT presentation. Antibodies to CD4, as well as soluble immunopurified gp120, blocked cell-mediated infection indicating that infection of T cells was through the CD4 molecule as has been demonstrated with cell-free virus. In addition, soluble gp120 inhibited Ag presentation by HIV-1-infected and uninfected MM. mAb to MHC class II Ag HLA-DR and -DP blocked T cell infection by HIV-1-infected MM with and without presentation of TT. No effect was observed with mAb to MHC class I Ag. These results indicate that virus transmission to T lymphocytes can be mediated by HIV-1-infected MM and that these cells maintain their function as APC. Activation of T cells appears to be important in the process of T cell infection in this system inasmuch as antibodies that block Ag presentation and thus a T cell proliferative signal inhibit infection.
Mann
D L
DL
Laboratory of Viral Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20895.
Gartner
S
S
Le Sane
F
F
Buchow
H
H
Popovic
M
M
D000938:Antigen-Presenting Cells / Q000276:immunology / Q000382:microbiology; D001667:Binding, Competitive; D015704:CD4 Antigens / Q000502:physiology; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015658:HIV Infections / Q000382:microbiology*; D015497:HIV-1 / Q000254:growth & development; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D008264:Macrophages / Q000382:microbiology*; D009000:Monocytes / Q000382:microbiology*; D012194:RNA-Directed DNA Polymerase / Q000032:analysis; D011991:Receptors, Virus / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D007376:Interleukin-2; D011991:Receptors, Virus; D012194:RNA-Directed DNA Polymerase