Related Experiment Videos
HIV-1 transmission and function of virus-infected monocytes/macrophages
D L Mann1, S Gartner, F Le Sane
1Laboratory of Viral Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20895.
Abstract:
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.
Insights
HIV-infected monocytes/macrophages can transmit the human immunodeficiency virus (HIV-1) to T lymphocytes. This virus transmission is enhanced by antigen presentation and involves the CD4 molecule and MHC class II, highlighting T cell activation
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Monocyte/macrophages (MM) play a crucial role in HIV-1 infection and pathogenesis.
- Understanding the mechanisms of HIV-1 transmission between immune cells is vital for developing therapeutic strategies.
Purpose of the Study:
- To investigate the ability of HIV-1-infected MM to infect autologous T lymphocytes.
- To explore the role of antigen presentation and specific molecular interactions in this cell-mediated infection process.
Main Methods:
- Isolation of monocytes/macrophages (MM) from HIV-1 seronegative and seropositive individuals.
- Co-culture of MM with autologous T lymphocytes, with and without exogenous antigen (tetanus toxin, streptokinase).
- Assessment of T cell proliferation ([3H]thymidine incorporation) and HIV-1 infection.
- Use of blocking antibodies against CD4, gp120, MHC class II (HLA-DR, -DP), and MHC class I antigens.
Main Results:
- HIV-1-infected MM stimulated T lymphocytes, with enhanced stimulation and infection observed during antigen presentation.
- Cell-mediated infection of T cells by HIV-1-infected MM was blocked by antibodies to CD4 and soluble gp120, indicating CD4-mediated entry.
- Soluble gp120 also inhibited antigen presentation by both infected and uninfected MM.
- MHC class II (HLA-DR, -DP) blocking antibodies inhibited T cell infection, while MHC class I antibodies had no effect.
- MM retained their antigen-presenting cell (APC) function even when infected with HIV-1.
Conclusions:
- HIV-1-infected MM can effectively mediate virus transmission to T lymphocytes.
- T cell activation, driven by antigen presentation via MM, is crucial for efficient T cell infection.
- The CD4 molecule and MHC class II antigens are critical for this MM-mediated HIV-1 transmission to T cells.