Lymph nodes harbor viral reservoirs that cause rebound of plasma viremia in SIV-infected macaques upon cessation of combined antiretroviral therapy

被引：98

作者：

Horiike, Mariko

Iwami, Shingo ^{[2
,3
]}

Kodama, Makoto ^{[4
]}

Sato, Akihiko ^{[4
]}

Watanabe, Yuji

Yasui, Mika

Ishida, Yuki

Kobayashi, Takeshi

Miura, Tomoyuki

Igarashi, Tatsuhiko ^{[1
]}

机构：

[1] Kyoto Univ, Inst Virus Res, Sakyo Ward, Expt Res Ctr Infect Dis,Lab Primate Model, Kyoto 6068507, Japan

[2] Japan Sci & Technol Agcy JST, Precursory Res Embryon Sci & Technol PRESTO, Kawaguchi, Saitama 3320012, Japan

[3] Univ Tokyo, Grad Sch Math Sci, Meguro Ku, Tokyo 1538914, Japan

[4] Shionogi & Co Ltd, Med Res Labs, Osaka 5660022, Japan

来源：

VIROLOGY | 2012年 / 423卷 / 02期

关键词：

SIV; Antiretroviral therapy; HIV-1; HAART; Rebound of plasma viremia; Reservoirs; Animal model; IMMUNODEFICIENCY-VIRUS TYPE-1; T-CELL DEPLETION; FOLLICULAR DENDRITIC CELLS; HIV-1; REPLICATION; PROLONGED SUPPRESSION; RESIDUAL VIREMIA; LATENT RESERVOIR; SURFACE-AREA; SHORT-TERM; DYNAMICS;

D O I：

10.1016/j.virol.2011.11.024

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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 Sly-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. (C) 2011 Elsevier Inc. All rights reserved.

引用

页码：107 / 118

页数：12

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