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Review
. 2016 Aug 12;90(17):7596-606.
doi: 10.1128/JVI.00672-16. Print 2016 Sep 1.

Macrophages in Progressive Human Immunodeficiency Virus/Simian Immunodeficiency Virus Infections

Sarah R DiNapoli  1 , Vanessa M Hirsch  2 , Jason M Brenchley  3
Affiliations
Review

Macrophages in Progressive Human Immunodeficiency Virus/Simian Immunodeficiency Virus Infections

Sarah R DiNapoli et al. J Virol. .

Abstract

The cells that are targeted by primate lentiviruses (HIV and simian immunodeficiency virus [SIV]) are of intense interest given the renewed effort to identify potential cures for HIV. These viruses have been reported to infect multiple cell lineages of hematopoietic origin, including all phenotypic and functional CD4 T cell subsets. The two most commonly reported cell types that become infected in vivo are memory CD4 T cells and tissue-resident macrophages. Though viral infection of CD4 T cells is routinely detected in both HIV-infected humans and SIV-infected Asian macaques, significant viral infection of macrophages is only routinely observed in animal models wherein CD4 T cells are almost entirely depleted. Here we review the roles of macrophages in lentiviral disease progression, the evidence that macrophages support viral replication in vivo, the animal models where macrophage-mediated replication of SIV is thought to occur, how the virus can interact with macrophages in vivo, pathologies thought to be attributed to viral replication within macrophages, how viral replication in macrophages might contribute to the asymptomatic phase of HIV/SIV infection, and whether macrophages represent a long-lived reservoir for the virus.

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Figures

FIG 1
FIG 1
Macrophage activation and subsequent contributions to systemic inflammation and disease progression. Macrophages can be activated by pathogens, microbial products, or proinflammatory cytokines. Activated macrophages then contribute to inflammation-associated pathologies, including fibrosis, cardiovascular disease, neurological disease, and bystander cell death in surrounding tissues.
FIG 2
FIG 2
Reported interactions of macrophages with HIV/SIV. (1) Direct infection by cell-free virus via CD4 and CCR5; (2) infection of macrophages via cell-to-cell transmission; (3) viral replication in macrophages; (4) clearance of infected dead or dying CD4 T cells via phagocytosis; (5) compartmentalization of virions in virus-containing compartments; and (6) phagocytosis of antibody-coated virions via Fc receptors (FcR) or complement receptors (CR).
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