Inhibition of HIV-1 Integration in Ex Vivo-Infected CD4 T Cells from Elite Controllers

被引：46

作者：

Buzon, Maria J. ^{[1
,2
]}

Seiss, Katherine ^{[2
]}

Weiss, Robert ^{[3
]}

Brass, Abraham L. ^{[2
]}

Rosenberg, Eric S. ^{[1
]}

Pereyra, Florencia ^{[2
,4
]}

Yu, Xu G. ^{[2
]}

Lichterfeld, Mathias ^{[1
]}

机构：

[1] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA

[2] Ragon Inst, Boston, MA USA

[3] Univ Calif Davis, Div Nephrol, Davis, CA 95616 USA

[4] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA

来源：

JOURNAL OF VIROLOGY | 2011年 / 85卷 / 18期

基金：

美国国家卫生研究院;

关键词：

DETERMINANTS;

D O I：

10.1128/JVI.05327-11

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Elite controllers spontaneously maintain undetectable levels of HIV-1 replication for reasons that remain unclear. Here, we show that in elite controllers, direct ex vivo infection of purified CD4 T cells without prior in vitro activation results in disproportionately low levels of integrated HIV-1 DNA relative to the quantity of reverse transcripts, while the levels of two-long terminal repeat (2-LTR) circles were excessively elevated relative to those of integrated HIV-1 DNA. This indicates that chromosomal HIV-1 integration is inhibited in ex vivo-infected CD4 T cells from elite controllers. This defect in HIV-1 integration was unrelated to p21, a host protein that can restrict early HIV-1 replication steps, and was not visible following infection of in vitro-activated CD4 T cells from elite controllers. These data contribute to increasing evidence that intrinsic inhibition of specific HIV-1 replication steps plays an important role in the ability of elite controllers to maintain undetectable viral loads.

引用

页码：9646 / 9650

页数：5

共 16 条

[1] The CDK Inhibitor p21Cip1/WAF1 Is Induced by FcγR Activation and Restricts the Replication of Human Immunodeficiency Virus Type 1 and Related Primate Lentiviruses in Human Macrophages [J].

Bergamaschi, Anna ;

David, Annie ;

Le Rouzie, Erwann ;

Nisole, Sebastien ;

Barre-Sinoussi, Francoise ;

Pancino, Gianfranco .

JOURNAL OF VIROLOGY, 2009, 83 (23) :12253-12265

[2] The 2010 scientific strategic plan of the Global HIV Vaccine Enterprise [J].

Berkley, Seth ;

Bertram, Kenneth ;

Delfraissy, Jean-Francois ;

Draghia-Akli, Ruxandra ;

Fauci, Anthony ;

Hallenbeck, Cynthia ;

Kagame, Madame Jeannette ;

Kim, Peter ;

Mafubelu, Daisy ;

Makgoba, Malegapuru W. ;

Piot, Peter ;

Walport, Mark ;

Warren, Mitchell ;

Yamada, Tadataka ;

Esparza, Jose ;

Hankins, Catherine ;

Johnston, Margaret I. ;

Levy, Yves ;

Romaris, Manuel ;

Ahmed, Rafi ;

Bernstein, Alan .

NATURE MEDICINE, 2010, 16 (09) :981-989

[3] HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells [J].

Betts, Michael R. ;

Nason, Martha C. ;

West, Sadie M. ;

De Rosa, Stephen C. ;

Migueles, Stephen A. ;

Abraham, Jonathan ;

Lederman, Michael M. ;

Benito, Jose M. ;

Goepfert, Paul A. ;

Connors, Mark ;

Roederer, Mario ;

Koup, Richard A. .

BLOOD, 2006, 107 (12) :4781-4789

[4]

Brass AL, 2008, SCIENCE, V319, P921, DOI 10.1126/science.1152725

[5] A quantitative assay for HIV DNA integration in vivo [J].

Butler, SL ;

Hansen, MST ;

Bushman, FD .

NATURE MEDICINE, 2001, 7 (05) :631-634

[6] HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAART-suppressed subjects [J].

Buzon, Maria J. ;

Massanella, Marta ;

Llibre, Josep M. ;

Esteve, Anna ;

Dahl, Viktor ;

Puertas, Maria C. ;

Gatell, Josep M. ;

Domingo, Pere ;

Paredes, Roger ;

Sharkey, Mark ;

Palmer, Sarah ;

Stevenson, Mario ;

Clotet, Bonaventura ;

Blanco, Julia ;

Martinez-Picado, Javier .

NATURE MEDICINE, 2010, 16 (04) :460-U143

[7] CD4+ T cells from elite controllers resist HIV-1 infection by selective upregulation of p21 [J].

Chen, Huabiao ;

Li, Chun ;

Huang, Jinghe ;

Cung, Thai ;

Seiss, Katherine ;

Beamon, Jill ;

Carrington, Mary F. ;

Porter, Lindsay C. ;

Burke, Patrick S. ;

Yang, Yue ;

Ryan, Bethany J. ;

Liu, Ruiwu ;

Weiss, Robert H. ;

Pereyra, Florencia ;

Cress, William D. ;

Brass, Abraham L. ;

Rosenberg, Eric S. ;

Walker, Bruce D. ;

Yu, Xu G. ;

Lichterfeld, Mathias .

JOURNAL OF CLINICAL INVESTIGATION, 2011, 121 (04) :1549-1560

[8] A whole-genome association study of major determinants for host control of HIV-1 [J].

Fellay, Jacques ;

Shianna, Kevin V. ;

Ge, Dongliang ;

Colombo, Sara ;

Ledergerber, Bruno ;

Weale, Mike ;

Zhang, Kunlin ;

Gumbs, Curtis ;

Castagna, Antonella ;

Cossarizza, Andrea ;

Cozzi-Lepri, Alessandro ;

De Luca, Andrea ;

Easterbrook, Philippa ;

Francioli, Patrick ;

Mallal, Simon ;

Martinez-Picado, Javier ;

Miro, Jose M. ;

Obel, Niels ;

Smith, Jason P. ;

Wyniger, Josiane ;

Descombes, Patrick ;

Antonarakis, Stylianos E. ;

Letvin, Norman L. ;

McMichael, Andrew J. ;

Haynes, Barton F. ;

Telenti, Amalio ;

Goldstein, David B. .

SCIENCE, 2007, 317 (5840) :944-947

[9] Elite Suppressors Harbor Low Levels of Integrated HIV DNA and High Levels of 2-LTR Circular HIV DNA Compared to HIV plus Patients On and Off HAART [J].

Graf, Erin H. ;

Mexas, Angela M. ;

Yu, Jianqing J. ;

Shaheen, Farida ;

Liszewski, Megan K. ;

Di Mascio, Michele ;

Migueles, Stephen A. ;

Connors, Mark ;

O'Doherty, Una .

PLOS PATHOGENS, 2011, 7 (02)

[10] High throughput screening of a small molecule one-bead-one-compound combinatorial library to identify attenuators of p21 as chemotherapy sensitizers [J].

Park, See-Hyoung ;

Wang, Xiaobing ;

Liu, Ruiwu ;

Lam, Kit S. ;

Weiss, Robert H. .

CANCER BIOLOGY & THERAPY, 2008, 7 (12) :2015-2022

← 1 2 →