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The role of mononuclear phagocytes in HTLV-III/LAV infection
Abstract:
Cells with properties characteristic of mononuclear phagocytes were evaluated for infectivity with five different isolates of the AIDS virus, HTLV-III/LAV. Mononuclear phagocytes cultured from brain and lung tissues of AIDS patients harbored the virus. In vitro-infected macrophages from the peripheral blood, bone marrow, or cord blood of healthy donors produced large quantities of virus. Virus production persisted for at least 40 days and was not dependent on host cell proliferation. Giant multinucleated cells were frequently observed in the macrophage cultures and numerous virus particles, often located within vacuole-like structures, were present in infected cells. The different virus isolates were compared for their ability to infect macrophages and T cells. Isolates from lung- and brain-derived macrophages had a significantly higher ability to infect macrophages than T cells. In contrast, the prototype HTLV-III beta showed a 10,000-fold lower ability to infect macrophages than T cells and virus production was one-tenth that in macrophage cultures infected with other isolates, indicating that a particular variant of HTLV-III/LAV may have a preferential tropism for macrophages or T cells. These results suggest that mononuclear phagocytes may serve as primary targets for infection and agents for virus dissemination and that these virus-infected cells may play a role in the pathogenesis of the disease.
Insights
Mononuclear phagocytes, a type of immune cell, can be infected by the AIDS virus (HTLV-III/LAV). These infected cells can produce large amounts of the virus, suggesting a role in disease spread.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Mononuclear phagocytes are critical immune cells involved in pathogen clearance.
- The human immunodeficiency virus (HIV), previously known as HTLV-III/LAV, causes Acquired Immunodeficiency Syndrome (AIDS).
- Understanding HIV tropism and cellular targets is crucial for comprehending AIDS pathogenesis.
Purpose of the Study:
- To investigate the infectivity of mononuclear phagocytes with different isolates of the AIDS virus (HTLV-III/LAV).
- To determine if mononuclear phagocytes from various sources can be infected and support viral replication.
- To compare the tropism of different HTLV-III/LAV isolates for macrophages versus T cells.
Main Methods:
- Culturing mononuclear phagocytes from AIDS patient tissues and healthy donor blood, bone marrow, and cord blood.
- In vitro infection of macrophages with five different HTLV-III/LAV isolates.
- Quantification of viral production and assessment of host cell proliferation.
- Microscopic examination of infected cells for viral particles and cytopathic effects.
- Comparative analysis of viral infectivity for macrophages and T cells.
Main Results:
- Mononuclear phagocytes from AIDS patients' brain and lung tissues harbored the virus.
- Macrophages infected in vitro produced substantial amounts of virus, with persistent production for over 40 days.
- Giant multinucleated cells and intracellular virus particles were observed in infected macrophages.
- HTLV-III/LAV isolates from lung and brain macrophages showed higher infectivity for macrophages than T cells.
- The prototype HTLV-III beta isolate exhibited significantly lower infectivity for macrophages compared to T cells, suggesting viral tropism variation.
Conclusions:
- Mononuclear phagocytes are susceptible to HTLV-III/LAV infection and can serve as a significant source of viral replication.
- Persistent virus production in macrophages, independent of cell proliferation, highlights their role in viral dissemination.
- Differential tropism among HTLV-III/LAV isolates suggests specific variants may target macrophages or T cells, impacting AIDS pathogenesis.