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Volume 8 Supplement 2

Frontiers of Retrovirology 2011

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HIV-1 infection in polarized primary macrophages


Macrophages are important targets for HIV-1 infection and are involved in mucosal transmission of the virus. Due to their ubiquitous distribution, macrophages play a crucial role in virus spread and can become reservoirs for HIV-1. In vivo, macrophages are exposed to a multiplicity of signals that can polarize them into a classically activated M1 (IFN-γ, LPS and/or TNF-α) or into alternatively activated M2a (IL-4, IL-13) and M2c (IL-10, glucocorticoids) phenotype. Previous studies have shown that the susceptibility of macrophages to HIV-1 infection is regulated by type I interferons (IFN-α, IFN-β) and by the cytokines IL-4 and IL-10, however the mechanism underlying the latter has not been described yet. In this study, the expression levels of HIV-1 restricting cellular factors in the different types of polarized monocyte-derived macrophages (MDM) was analyzed and their role in HIV-1 susceptibility was investigated.


Monocytes were isolated from buffy coats from healthy blood donors using density gradient separation followed by plastic adherence. MDM with a M1, M2a and M2c phenotype were obtained by culturing cells for 5 days in the presence of IFN-γ, IFN-γ/TNF-α, IL-4 and IL-10, respectively. Monocytes were also stimulated with type I interferons and the colony-stimulating factors M-CSF and GM-CSF. Polarization of MDM was confirmed by flow cytometry. MDM susceptibility to infection was analyzed with HIV-1/NL4-3BaL and a VSV-G-pseudotyped luciferase reporter virus. Expression of HIV-1 host restriction factors was measured by RT-qPCR. Viral reverse transcription products were detected, in order to identify at which step inhibition of viral replication occurs.


Macrophages differentiated in the presence of IFN-α, IFN-β, IFN-γ ± TNF-α (M1), IL-4 (M2a) or IL-10 (M2c), differentially expressed characteristic membrane receptors, such as CD14, CD16, CD64, CD80, CD162, CD200R and CD206, confirming the activated/polarized phenotype. Unpolarized and M-CSF/GM-CSF-stimulated MDM were highly susceptible to infection, whereas IFN-α, IFN-β, IFN-γ±TNF-α, IL-4 or IL-10 treatment resulted in a significant inhibition of virus replication. Infection of these populations with a VSV-G-pseudotyped virus indicated that HIV-1 replication was inhibited at a post-entry level. Inhibition of viral replication occurs at an early step in the replication cycle, in MDM stimulated with type I interferons and in M1 and M2a MDM, whereas in M2c macrophages, inhibition occurs after reverse trannscription. Expression of HIV-1 restriction factors like APOBEC3G, Trim5α, CyPA, tetherin, Trim22 and recently identified anti-HIV miRNAs was upregulated in MDM treated with type I IFNs, and to a lesser extend in M1 polarized macrophages.


These results suggest that the host factors analyzed here may contribute to inhibition of HIV-1 replication in MDM by type I interferons. However, these factors are not likely involved in HIV-1 inhibition in M1 or M2 macrophages. Additional studies are necessary to identify other host factors involved in the resistance of polarized macrophages to HIV-1 infection.

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This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Cobos-Jiménez, V., de Taeve, S.W., Booiman, T. et al. HIV-1 infection in polarized primary macrophages. Retrovirology 8 (Suppl 2), P11 (2011).

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