Multiple Origins of Virus Persistence during Natural Control of HIV Infection

被引：146

作者：

Boritz, Eli A. ^{[1
]}

Darko, Samuel ^{[1
]}

Swaszek, Luke ^{[1
]}

Wolf, Gideon ^{[1
]}

Wells, David ^{[2
]}

Wu, Xiaolin ^{[2
]}

Henry, Amy R. ^{[1
]}

Laboune, Farida ^{[1
]}

Hu, Jianfei ^{[1
]}

Ambrozak, David ^{[3
]}

Hughes, Marybeth S. ^{[4
]}

Hoh, Rebecca ^{[5
]}

Casazza, Joseph P. ^{[3
]}

Vostal, Alexander

Bunis, Daniel ^{[1
]}

Nganou-Makamdop, Krystelle ^{[1
]}

Lee, James S. ^{[1
]}

Migueles, Stephen A. ^{[6
]}

Koup, Richard A. ^{[3
]}

Connors, Mark ^{[6
]}

Moir, Susan ^{[6
]}

Schacker, Timothy ^{[8
]}

Maldarelli, Frank ^{[7
]}

Hughes, Stephen H. ^{[7
]}

Deeks, Steven G. ^{[5
]}

Douek, Daniel C. ^{[1
]}

机构：

[1] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA

[2] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA

[3] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA

[4] NCI, Thorac & Gastrointestinal Oncol Branch, NIH, Bethesda, MD 20892 USA

[5] Univ Calif San Francisco, Dept Med, San Francisco, CA 94110 USA

[6] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA

[7] NCI, HIV Dynam & Replicat Program, NIH, Frederick, MD 21702 USA

[8] Univ Minnesota, Dept Med, Program HIV Med, Minneapolis, MN 55455 USA

来源：

CELL | 2016年 / 166卷 / 04期

关键词：

ACTIVE ANTIRETROVIRAL THERAPY; CD4(+) T-CELLS; ELITE SUPPRESSORS; LATENT RESERVOIR; IN-VIVO; REPLICATION; PROLIFERATION; TYPE-1; LYMPHOCYTES; ACTIVATION;

D O I：

10.1016/j.cell.2016.06.039

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Targeted HIV cure strategies require definition of the mechanisms that maintain the virus. Here, we tracked HIV replication and the persistence of infected CD4 T cells in individuals with natural virologic control by sequencing viruses, T cell receptor genes, HIV integration sites, and cellular transcriptomes. Our results revealed three mechanisms of HIV persistence operating within distinct anatomic and functional compartments. In lymph node, we detected viruses with genetic and transcriptional attributes of active replication in both T follicular helper (T-FH) cells and non-T-FH memory cells. In blood, we detected inducible proviruses of archival origin among highly differentiated, clonally expanded cells. Linking the lymph node and blood was a small population of circulating cells harboring inducible proviruses of recent origin. Thus, HIV replication in lymphoid tissue, clonal expansion of infected cells, and recirculation of recently infected cells act together to maintain the virus in HIV controllers despite effective antiviral immunity.

引用

页码：1004 / 1015

页数：12

共 40 条

[21] Reservoir expansion by T-cell proliferation may be another barrier to curing HIV infection [J].

Kim, Michelle ;

Siliciano, Robert F. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2016, 113 (07) :1692-1694

[22] Evidence for Innate Immune System Activation in HIV Type 1-Infected Elite Controllers [J].

Krishnan, Sonya ;

Wilson, Eleanor M. P. ;

Sheikh, Virginia ;

Rupert, Adam ;

Mendoza, Daniel ;

Yang, Jun ;

Lempicki, Richard ;

Migueles, Stephen A. ;

Sereti, Irini .

JOURNAL OF INFECTIOUS DISEASES, 2014, 209 (06) :931-939

[23] Specific HIV integration sites are linked to clonal expansion and persistence of infected cells [J].

Maldarelli, F. ;

Wu, X. ;

Su, L. ;

Simonetti, F. R. ;

Shao, W. ;

Hill, S. ;

Spindler, J. ;

Ferris, A. L. ;

Mellors, J. W. ;

Kearney, M. F. ;

Coffin, J. M. ;

Hughes, S. H. .

SCIENCE, 2014, 345 (6193) :179-183

[24] HIV-1 Continues To Replicate and Evolve in Patients with Natural Control of HIV Infection [J].

Mens, Helene ;

Kearney, Mary ;

Wiegand, Ann ;

Shao, Wei ;

Schonning, Kristian ;

Gerstoft, Jan ;

Obel, Niels ;

Maldarelli, Frank ;

Mellors, John W. ;

Benfield, Thomas ;

Coffin, John M. .

JOURNAL OF VIROLOGY, 2010, 84 (24) :12971-12981

[25] Success and failure of the cellular immune response against HIV-1 [J].

Migueles, Stephen A. ;

Connors, Mark .

NATURE IMMUNOLOGY, 2015, 16 (06) :563-570

[26] Control of HIV-1 in Elite Suppressors despite Ongoing Replication and Evolution in Plasma Virus [J].

O'Connell, Karen A. ;

Brennan, Timothy P. ;

Bailey, Justin R. ;

Ray, Stuart C. ;

Siliciano, Robert F. ;

Blankson, Joel N. .

JOURNAL OF VIROLOGY, 2010, 84 (14) :7018-7028

[27] Follicular helper T cells serve as the major CD4 T cell compartment for HIV-1 infection, replication, and production [J].

Perreau, Matthieu ;

Savoye, Anne-Laure ;

De Crignis, Elisa ;

Corpataux, Jean-Marc ;

Cubas, Rafael ;

Haddad, Elias K. ;

De Leval, Laurence ;

Graziosi, Cecilia ;

Pantaleo, Giuseppe .

JOURNAL OF EXPERIMENTAL MEDICINE, 2013, 210 (01) :143-156

[28] ALTERNATIVE SPLICING OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 MESSENGER-RNA MODULATES VIRAL PROTEIN EXPRESSION, REPLICATION, AND INFECTIVITY [J].

PURCELL, DFJ ;

MARTIN, MA .

JOURNAL OF VIROLOGY, 1993, 67 (11) :6365-6378

[29] Panobinostat, a histone deacetylase inhibitor, for latent-virus reactivation in HIV-infected patients on suppressive antiretroviral therapy: a phase 1/2, single group, clinical trial [J].

Rasmussen, Thomas A. ;

Tolstrup, Martin ;

Brinkmann, Christel R. ;

Olesen, Rikke ;

Erikstrup, Christian ;

Solomon, Ajantha ;

Winckelmann, Anni ;

Palmer, Sarah ;

Dinarello, Charles ;

Buzon, Maria ;

Lichterfeld, Mathias ;

Lewin, Sharon R. ;

Ostergaard, Lars ;

Sogaard, Ole S. .

LANCET HIV, 2014, 1 (01) :E13-E21

[30] Large number of rebounding/founder HIV variants emerge from multifocal infection in lymphatic tissues after treatment interruption [J].

Rothenberger, Meghan K. ;

Keele, Brandon F. ;

Wietgrefe, Stephen W. ;

Fletcher, Courtney V. ;

Beilman, Gregory J. ;

Chipman, Jeffrey G. ;

Khoruts, Alexander ;

Estes, Jacob D. ;

Anderson, Jodi ;

Callisto, Samuel P. ;

Schmidt, Thomas E. ;

Thorkelson, Ann ;

Reilly, Cavan ;

Perkey, Katherine ;

Reimann, Thomas G. ;

Utay, Netanya S. ;

Makamdop, Krystelle Nganou ;

Stevenson, Mario ;

Douek, Daniel C. ;

Haase, Ashley T. ;

Schacker, Timothy W. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2015, 112 (10) :E1126-E1134

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