title: Lymph nodes harbor viral reservoirs that cause rebound of plasma viremia in SIV-infected macaques upon cessation of combined antiretroviral therapy.
abstract: Attempts to find a cure for HIV infection are hindered by the presence of viral reservoirs that resist highly active antiretroviral therapy. To identify the properties of these reservoirs, four SIV239-infected Rhesus macaques were treated with combined antiretroviral therapy (cART) for 1 year. While plasma viral RNA (vRNA) was effectively suppressed, a systemic analysis revealed that vRNA was distributed in the following order: lymphatic tissues>lungs and intestine>other tissues. Histochemistry yielded no cells with viral signals. To increase the chance of detection, two additional SIV-infected animals were treated and analyzed on Day 10 after the cessation of cART. These animals exhibited similar vRNA distribution patterns to the former animals, and immunohistochemistry revealed Nef-positive T lymphocytes predominantly in the follicles of mesenteric lymph nodes (MLNs). These data suggest that lymphatic tissues, including MLNs, contain major cellular reservoirs that cause rebound of plasma viremia upon cessation of therapy.
authors.affiliation: Laboratory of Primate Model, Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Horiike
authors.forename: Shingo
authors.initials: S
authors.lastname: Iwami
authors.forename: Makoto
authors.initials: M
authors.lastname: Kodama
authors.forename: Akihiko
authors.initials: A
authors.lastname: Sato
authors.forename: Yuji
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Mika
authors.initials: M
authors.lastname: Yasui
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ishida
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Miura
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Igarashi
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D004195:Disease Models, Animal; D004197:Disease Reservoirs / Q000821:virology*; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008198:Lymph Nodes / Q000821:virology*; D008253:Macaca mulatta; D012008:Recurrence; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000187:drug effects / Q000502:physiology*; D017735:Virus Latency; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents