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Updated: May 17, 2026
Isolation, Transfection, and Culture of Primary Human Monocytes
Published on: December 16, 2019
Differential expression of HIV-1 interfering factors in monocyte-derived macrophages stimulated with polarizing
Viviana Cobos Jiménez1, Thijs Booiman, Steven W de Taeye
1Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, and Center for Infectious Diseases and Immunity Amsterdam-CINIMA at the Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
Abstract:
HIV-1 replication in macrophages can be regulated by cytokines and infection is restricted in macrophages activated by type I interferons and polarizing cytokines. Here, we observed that the expression levels of the cellular factors Trim5α, CypA, APOBEC3G, SAMHD-1, Trim22, tetherin and TREX-1, and the anti-HIV miRNAs miR-28, miR-150, miR-223 and miR-382 was upregulated by IFN-α and IFN-β in macrophages, which may account for the inhibiting effect on viral replication and the antiviral state of these cells. Expression of these factors was also increased by IFN-γ +/- TNF-α, albeit to a lesser extent; yet, HIV-1 replication in these cells was not restricted at the level of proviral synthesis, indicating that these cellular factors only partially contribute to the observed restriction. IL-4, IL-10 or IL-32 polarization did not affect the expression of cellular factors and miRNAs, suggesting only a limited role for these cellular factors in restricting HIV-1 replication in macrophages.
Insights
Type I interferons upregulate antiviral factors in macrophages, inhibiting HIV-1 replication. Other cytokines have a limited effect, suggesting specific pathways are key to controlling HIV-1 infection in these cells.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Macrophages play a critical role in HIV-1 infection and pathogenesis.
- Cytokine-mediated regulation influences HIV-1 replication within macrophages.
- Understanding cellular restriction factors is crucial for developing antiviral strategies.
Purpose of the Study:
- To investigate the impact of various cytokines on the expression of cellular antiviral factors and microRNAs in macrophages.
- To determine the role of these upregulated factors in restricting HIV-1 replication.
- To elucidate the differential effects of Type I interferons versus other polarizing cytokines on macrophage antiviral states.
Main Methods:
- Macrophage cultures were treated with different cytokines, including IFN-α, IFN-β, IFN-γ, TNF-α, IL-4, IL-10, and IL-32.
- Quantitative analysis of cellular restriction factors (Trim5α, CypA, APOBEC3G, SAMHD-1, Trim22, tetherin, TREX-1) and anti-HIV microRNAs (miR-28, miR-150, miR-223, miR-382) was performed.
- HIV-1 replication levels were assessed in treated macrophages.
Main Results:
- Type I interferons (IFN-α and IFN-β) significantly upregulated multiple cellular antiviral factors and anti-HIV microRNAs in macrophages.
- This upregulation by Type I interferons correlated with an inhibiting effect on HIV-1 replication and establishment of an antiviral state.
- IFN-γ +/- TNF-α also increased factor expression but resulted in less restriction of proviral synthesis, indicating partial contribution.
- IL-4, IL-10, and IL-32 polarization showed no significant effect on these cellular factors or HIV-1 replication.
Conclusions:
- Type I interferons are potent inducers of cellular antiviral mechanisms in macrophages, effectively restricting HIV-1 replication.
- While other cytokines like IFN-γ can induce some antiviral factors, their contribution to overall HIV-1 restriction in macrophages is limited.
- Specific cellular factors and miRNAs modulated by Type I interferons are key determinants of the antiviral state in macrophages against HIV-1.
