title: Tissue-resident macrophages can contain replication-competent virus in antiretroviral-naive, SIV-infected Asian macaques.
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.affiliation: Laboratory of Parasitic Diseases.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: DiNapoli
authors.affiliation: Laboratory of Parasitic Diseases.
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Ortiz
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
authors.forename: Fan
authors.initials: F
authors.lastname: Wu
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
authors.forename: Kenta
authors.initials: K
authors.lastname: Matsuda
authors.affiliation: Department of Medicine, Indiana University, Indianapolis, Indiana, USA.
authors.forename: Homer L
authors.initials: HL
authors.lastname: Twigg
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: Hirsch
authors.affiliation: Department of Medicine, University of Arizona, Tucson, Arizona, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Knox
authors.affiliation: Laboratory of Parasitic Diseases.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Brenchley
mesh_terms: D000818:Animals; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology; D004279:DNA, Viral / Q000378:metabolism*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D016180:Lentivirus Infections / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D008221:Lymphoid Tissue / Q000166:cytology; D008251:Macaca; D008253:Macaca mulatta; D008254:Macaca nemestrina; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000502:physiology; D019562:Viral Load; D014779:Virus Replication
chemical_list: D044966:Anti-Retroviral Agents; D004279:DNA, Viral