Generation of HIV Latency in Humanized BLT Mice

被引：156

作者：

Denton, Paul W. ^{[1
]}

Olesen, Rikke ^{[1
,4
]}

Choudhary, Shailesh K. ^{[1
]}

Archin, Nancy M. ^{[1
]}

Wahl, Angela ^{[1
]}

Swanson, Michael D. ^{[1
]}

Chateau, Morgan ^{[1
]}

Nochi, Tomonori ^{[1
]}

Krisko, John F. ^{[1
]}

Spagnuolo, Rae Ann ^{[1
]}

Margolis, David M. ^{[1
,2
,3
]}

Garcia, J. Victor ^{[1
]}

机构：

[1] Univ N Carolina, Dept Internal Med, Div Infect Dis, Ctr AIDS Res, Chapel Hill, NC 27599 USA

[2] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC USA

[3] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA

[4] Aarhus Univ Hosp, Dept Infect Dis, Sheiby, Denmark

来源：

JOURNAL OF VIROLOGY | 2012年 / 86卷 / 01期

基金：

美国国家卫生研究院; 日本学术振兴会;

关键词：

ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; VIRAL RESERVOIRS; IMMUNE-ACTIVATION; PLASMA VIREMIA; VALPROIC ACID; T-CELLS; INFECTION; MODEL; TRANSMISSION;

D O I：

10.1128/JVI.06120-11

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Here we demonstrate that a combination of tenofovir, emtricitabine, and raltegravir effectively suppresses peripheral and systemic HIV replication in humanized BLT mice. We also demonstrate that antiretroviral therapy (ART)-treated humanized BLT mice harbor latently infected resting human CD4(+) T cells that can be induced ex vivo to produce HIV. We observed that the levels of infected resting human CD4(+) T cells present in BLT mice are within the range of those observed circulating in patients undergoing suppressive ART. These results demonstrate the potential of humanized BLT mice as an attractive model for testing the in vivo efficacy of novel HIV eradication strategies.

引用

页码：630 / 634

页数：5

共 39 条

[1] Valproic acid without intensified antiviral therapy has limited impact on persistent HIV infection of resting CD4+ T cells
Archin, Nancy M.
Eron, Joseph J.
Palmer, Sarah
Hartmann-Duff, Anne
Martinson, Jeffery A.
Wiegand, Ann
Bandarenko, Nicholas
Schmitz, John L.
Bosch, Ronald J.
Landay, Alan L.
Coffin, John M.
Margolis, David M.
[J]. AIDS, 2008, 22 (10) : 1131 - 1135
[2] Biphasic decay of latently infected CD4+ T cells in acute human immunodeficiency virus type 1 infection
Blankson, JN
Finzi, D
Pierson, TC
Sabundayo, BP
Chadwick, K
Margolick, JB
Quinn, TC
Siliciano, RF
[J]. JOURNAL OF INFECTIOUS DISEASES, 2000, 182 (06) : 1636 - 1642
[3] Induction of Robust Cellular and Humoral Virus-Specific Adaptive Immune Responses in Human Immunodeficiency Virus-Infected Humanized BLT Mice
Brainard, Diana M.
Seung, Edward
Frahm, Nicole
Cariappa, Annaiah
Bailey, Charles C.
Hart, William K.
Shin, Hae-Sook
Brooks, Sarah F.
Knight, Heather L.
Eichbaum, Quentin
Yang, Yong-Guang
Sykes, Megan
Walker, Bruce D.
Freeman, Gordon J.
Pillai, Shiv
Westmoreland, Susan V.
Brander, Christian
Luster, Andrew D.
Tager, Andrew M.
[J]. JOURNAL OF VIROLOGY, 2009, 83 (14) : 7305 - 7321
[4] Curing HIV: Pharmacologic Approaches to Target HIV-1 Latency
Choudhary, Shailesh K.
Margolis, David M.
[J]. ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 51, 2011, 2011, 51 : 397 - 418
[5] Persistence of HIV in gut-associated lymphoid tissue despite long-term antiretroviral therapy
Chun, Tae-Wook
Nickle, David C.
Justement, Jesse S.
Meyers, Jennifer H.
Roby, Gregg
Hallahan, Claire W.
Kottilil, Shyam
Moir, Susan
Mican, Joann M.
Mullins, James I.
Ward, Douglas J.
Kovacs, Joseph A.
Mannon, Peter J.
Fauci, Anthony S.
[J]. JOURNAL OF INFECTIOUS DISEASES, 2008, 197 (05) : 714 - 720
[6] Rebound of plasma viremia following cessation of antiretroviral therapy despite profoundly low levels of HIV reservoir: implications for eradication
Chun, Tae-Wook
Justement, J. Shawn
Murray, Danielle
Hallahan, Claire W.
Maenza, Janine
Collier, Ann C.
Sheth, Prameet M.
Kaul, Rupert
Ostrowski, Mario
Moir, Susan
Kovacs, Colin
Fauci, Anthony S.
[J]. AIDS, 2010, 24 (18) : 2803 - 2808
[7] Quantification of latent tissue reservoirs and total body viral load in HIV-1 Infection
Chun, TW
Carruth, L
Finzi, D
Shen, XF
DiGiuseppe, JA
Taylor, H
Hermankova, M
Chadwick, K
Margolick, J
Quinn, TC
Kuo, YH
Brookmeyer, R
Zeiger, MA
BarditchCrovo, P
Siliciano, RF
[J]. NATURE, 1997, 387 (6629) : 183 - 188
[8] Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy
Chun, TW
Stuyver, L
Mizell, SB
Ehler, LA
Mican, JAM
Baseler, M
Lloyd, AL
Nowak, MA
Fauci, AS
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (24) : 13193 - 13197
[9] Simian immunodeficiency virus macaque models of HIV latency
Deere, Jesse D.
Schinazi, Raymond F.
North, Thomas W.
[J]. CURRENT OPINION IN HIV AND AIDS, 2011, 6 (01) : 57 - 61
[10] One Percent Tenofovir Applied Topically to Humanized BLT Mice and Used According to the CAPRISA 004 Experimental Design Demonstrates Partial Protection from Vaginal HIV Infection, Validating the BLT Model for Evaluation of New Microbicide Candidates
Denton, Paul W.
Othieno, Florence
Martinez-Torres, Francisco
Zou, Wei
Krisko, John F.
Fleming, Elisa
Zein, Sima
Powell, Daniel A.
Wahl, Angela
Kwak, Youn Tae
Welch, Brett D.
Kay, Michael S.
Payne, Deborah A.
Gallay, Philippe
Appella, Ettore
Estes, Jacob D.
Lu, Min
Garcia, J. Victor
[J]. JOURNAL OF VIROLOGY, 2011, 85 (15) : 7582 - 7593

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