Related Experiment Videos
Endogenous macrophage CSF production is associated with viral replication in HIV-1-infected human monocyte-derived
M F Gruber1, K A Weih, E J Boone
1Division of Cytokine Biology, Food and Drug Administration, Bethesda, MD 20892, USA.
Abstract:
Human monocyte-derived macrophages (MDM) cultured in medium containing macrophage (M) CSF are more susceptible to infection with HIV-1. M-CSF increases the frequency with which MDM become infected, the level of HIV mRNA expressed per infected cell, and the level of proviral DNA expressed per infected culture. Because of these effects of M-CSF on HIV-1 replication and the reported function of this factor as a survival and differentiation factor for human monocytes, we investigated whether HIV-1 could induce endogenous M-CSF production by MDM and the potential role of endogenous M-CSF on HIV-1 infection in these cells. MDM infected with HIV and maintained in the absence of exogenous M-CSF produced this cytokine endogenously at levels 5- to 24-fold higher than uninfected cells. In contrast, the proinflammatory cytokines IL-1, IL-6, and TNF-alpha and the growth factor granulocyte-macrophage CSF were not detected. The kinetics of M-CSF production following infection paralleled the kinetics of virus replication. Furthermore, enhanced production of M-CSF was dependent on viral entry and active replication of HIV-1. Thus, endogenous M-CSF production may contribute to the survival of HIV-infected MDM, enable them to function as a reservoir for HIV, and facilitate the spread of virus in vivo.
Insights
Human immunodeficiency virus type 1 (HIV-1) infection stimulates macrophages to produce macrophage colony-stimulating factor (M-CSF). This endogenous M-CSF may enhance HIV-1 replication and promote virus spread.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Macrophage colony-stimulating factor (M-CSF) promotes human monocyte-derived macrophage (MDM) survival and differentiation.
- M-CSF enhances susceptibility to human immunodeficiency virus type 1 (HIV-1) infection, increasing viral replication markers.
Purpose of the Study:
- To investigate if HIV-1 infection induces endogenous M-CSF production in MDM.
- To determine the role of endogenously produced M-CSF in HIV-1 infection.
Main Methods:
- MDM were infected with HIV-1 and cultured without exogenous M-CSF.
- M-CSF levels in culture supernatants were quantified using enzyme-linked immunosorbent assays.
- Viral replication was assessed by measuring HIV mRNA and proviral DNA levels.
Main Results:
- HIV-1 infected MDM produced significantly higher levels of endogenous M-CSF (5- to 24-fold) compared to uninfected cells.
- Endogenous M-CSF production correlated with viral replication kinetics and was dependent on viral entry and active replication.
- Pro-inflammatory cytokines (IL-1, IL-6, TNF-alpha) and granulocyte-macrophage CSF were not detected.
Conclusions:
- HIV-1 infection induces endogenous M-CSF production by MDM.
- Endogenous M-CSF may contribute to the survival of HIV-1-infected macrophages, facilitating viral reservoirs and in vivo spread.