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Tissue-resident macrophages can contain replication-competent virus in antiretroviral-naive, SIV-infected Asian macaques
Sarah R. DiNapoli, Alexandra M. Ortiz, Fan Wu, Kenta Matsuda, Homer L. Twigg III, Vanessa M. Hirsch, Kenneth Knox, Jason M. Brenchley
Sarah R. DiNapoli, Alexandra M. Ortiz, Fan Wu, Kenta Matsuda, Homer L. Twigg III, Vanessa M. Hirsch, Kenneth Knox, Jason M. Brenchley
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Research Article AIDS/HIV

Tissue-resident macrophages can contain replication-competent virus in antiretroviral-naive, SIV-infected Asian macaques

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Abstract

SIV DNA can be detected in lymphoid tissue–resident macrophages of chronically SIV-infected Asian macaques. These macrophages also contain evidence of recently phagocytosed SIV-infected CD4+ T cells. Here, we examine whether these macrophages contain replication-competent virus, whether viral DNA can be detected in tissue-resident macrophages from antiretroviral (ARV) therapy–treated animals and humans, and how the viral sequences amplified from macrophages and contemporaneous CD4+ T cells compare. In ARV-naive animals, we find that lymphoid tissue–resident macrophages contain replication-competent virus if they also contain viral DNA in ARV-naive Asian macaques. The genetic sequence of the virus within these macrophages is similar to those within CD4+ T cells from the same anatomic sites. In ARV-treated animals, we find that viral DNA can be amplified from lymphoid tissue–resident macrophages of SIV-infected Asian macaques that were treated with ARVs for at least 5 months, but we could not detect replication-competent virus from macrophages of animals treated with ARVs. Finally, we could not detect viral DNA in alveolar macrophages from HIV-infected individuals who received ARVs for 3 years and had undetectable viral loads. These data demonstrate that macrophages can contain replication-competent virus, but may not represent a significant reservoir for HIV in vivo.

Authors

Sarah R. DiNapoli, Alexandra M. Ortiz, Fan Wu, Kenta Matsuda, Homer L. Twigg III, Vanessa M. Hirsch, Kenneth Knox, Jason M. Brenchley

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Figure 2

Phylogenetic distribution of Env sequences from co-culture and contemporaneous plasma.

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Phylogenetic distribution of Env sequences from co-culture and contempor...
Viral RNA from cell culture media and necropsy plasma was isolated and sequenced for the variable regions 1–4 (V1–V4) of Env. Phylogenies constructed using the neighbor-joining method and Kimura 2-parameter model illustrate the genetic distribution of viruses from cocultures and plasma for each animal: (A) PT99P052, (B) RhDB92, (C) Rh848, and (D) Rh591. Identical sequences are grouped with the number of sequences indicated in parentheses. Sequence source is indicated by color: macrophage coculture (blue), CD4+ T cell coculture (red), and contemporaneous plasma (green). Branch length is indicated per animal. Root SIV Env sequences were obtained from the NCBI Nucleotide database.

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