TY - JOUR
T1 - Lymph nodes harbor viral reservoirs that cause rebound of plasma viremia in SIV-infected macaques upon cessation of combined antiretroviral therapy
AU - Horiike, Mariko
AU - Iwami, Shingo
AU - Kodama, Makoto
AU - Sato, Akihiko
AU - Watanabe, Yuji
AU - Yasui, Mika
AU - Ishida, Yuki
AU - Kobayashi, Takeshi
AU - Miura, Tomoyuki
AU - Igarashi, Tatsuhiko
N1 - Funding Information:
The authors are in debt to Drs. T. Sata and S. Nakamura for technical advice and critique on histochemical staining, Dr. A. Nomoto for continuous support, and member of the Igarashi laboratory for assistance of animal procedures and analyses. This work was supported by Research on HIV/AIDS [ 08062160 to T.I.] from the Ministry of Health, Labor and Welfare of Japan . S.I. was supported by JST PRESTO program.
PY - 2012/2/20
Y1 - 2012/2/20
N2 - 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.
AB - 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.
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U2 - 10.1016/j.virol.2011.11.024
DO - 10.1016/j.virol.2011.11.024
M3 - Article
C2 - 22196013
AN - SCOPUS:84855767273
SN - 0042-6822
VL - 423
SP - 107
EP - 118
JO - Virology
JF - Virology
IS - 2
ER -
