Multiple Origins of Virus Persistence during Natural Control of HIV Infection

Eli A. Boritz; Samuel Darko; Luke Swaszek; Gideon Wolf; David Wells; Xiaolin Wu; Amy R. Henry; Farida Laboune; Jianfei Hu; David Ambrozak; Marybeth S. Hughes; Rebecca Hoh; Joseph P. Casazza; Alexander Vostal; Daniel Bunis; Krystelle Nganou-Makamdop; James S. Lee; Stephen A. Migueles; Richard A. Koup; Mark Connors; Susan Moir; Timothy Schacker; Frank Maldarelli; Stephen H. Hughes; Steven G. Deeks; Daniel C. Douek

doi:10.1016/j.cell.2016.06.039

Multiple Origins of Virus Persistence during Natural Control of HIV Infection

Eli A. Boritz, Samuel Darko, Luke Swaszek, Gideon Wolf, David Wells, Xiaolin Wu, Amy R. Henry, Farida Laboune, Jianfei Hu, David Ambrozak, Marybeth S. Hughes, Rebecca Hoh, Joseph P. Casazza, Alexander Vostal, Daniel Bunis, Krystelle Nganou-Makamdop, James S. Lee, Stephen A. Migueles, Richard A. Koup, Mark ConnorsSusan Moir, Timothy Schacker, Frank Maldarelli, Stephen H. Hughes, Steven G. Deeks, Daniel C. Douek

Medicine - Infectious Disease and International Medicine

Research output: Contribution to journal › Article › peer-review

120 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1004-1015
Number of pages	12
Journal	Cell
Volume	166
Issue number	4
DOIs	https://doi.org/10.1016/j.cell.2016.06.039
State	Published - Aug 11 2016

Bibliographical note

Funding Information:
We thank the study participants for their involvement in the study. We thank S. Kosakovsky-Pond for help with phylogenetic analysis and C. Petrovas for helpful discussions. D.C.D. and E.A.B. are funded by the NIH Intramural Research Program. D.C.D. is also funded by the NIAID Division of AIDS and the NIH Office of AIDS Research. Additional funding came from AIDS Vaccine Discovery grant OPP1032325 from the Bill and Melinda Gates Foundation (to R.A.K.), the Delaney AIDS Research Enterprise (AI096109 to S.G.D.), NIAID K24 (AI069994 to S.G.D.), the UCSF/Gladstone Institute of Virology & Immunology CFAR (P30 AI027763 to S.G.D.), and federal funds from the NCI (to F.M. and S.H.H.).

Publisher Copyright:
© 2016

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Publisher link

10.1016/j.cell.2016.06.039

Find It

Find It at U of M Libraries

Cite this

Boritz, E. A., Darko, S., Swaszek, L., Wolf, G., Wells, D., Wu, X., Henry, A. R., Laboune, F., Hu, J., Ambrozak, D., Hughes, M. S., Hoh, R., Casazza, J. P., Vostal, A., Bunis, D., Nganou-Makamdop, K., Lee, J. S., Migueles, S. A., Koup, R. A., ... Douek, D. C. (2016). Multiple Origins of Virus Persistence during Natural Control of HIV Infection. Cell, 166(4), 1004-1015. https://doi.org/10.1016/j.cell.2016.06.039

Boritz, EA, Darko, S, Swaszek, L, Wolf, G, Wells, D, Wu, X, Henry, AR, Laboune, F, Hu, J, Ambrozak, D, Hughes, MS, Hoh, R, Casazza, JP, Vostal, A, Bunis, D, Nganou-Makamdop, K, Lee, JS, Migueles, SA, Koup, RA, Connors, M, Moir, S, Schacker, T, Maldarelli, F, Hughes, SH, Deeks, SG & Douek, DC 2016, 'Multiple Origins of Virus Persistence during Natural Control of HIV Infection', Cell, vol. 166, no. 4, pp. 1004-1015. https://doi.org/10.1016/j.cell.2016.06.039

@article{9c18b770223e47228cf006a33826082e,

title = "Multiple Origins of Virus Persistence during Natural Control of HIV Infection",

abstract = "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 (TFH) cells and non-TFH 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.",

author = "Boritz, {Eli A.} and Samuel Darko and Luke Swaszek and Gideon Wolf and David Wells and Xiaolin Wu and Henry, {Amy R.} and Farida Laboune and Jianfei Hu and David Ambrozak and Hughes, {Marybeth S.} and Rebecca Hoh and Casazza, {Joseph P.} and Alexander Vostal and Daniel Bunis and Krystelle Nganou-Makamdop and Lee, {James S.} and Migueles, {Stephen A.} and Koup, {Richard A.} and Mark Connors and Susan Moir and Timothy Schacker and Frank Maldarelli and Hughes, {Stephen H.} and Deeks, {Steven G.} and Douek, {Daniel C.}",

note = "Funding Information: We thank the study participants for their involvement in the study. We thank S. Kosakovsky-Pond for help with phylogenetic analysis and C. Petrovas for helpful discussions. D.C.D. and E.A.B. are funded by the NIH Intramural Research Program. D.C.D. is also funded by the NIAID Division of AIDS and the NIH Office of AIDS Research. Additional funding came from AIDS Vaccine Discovery grant OPP1032325 from the Bill and Melinda Gates Foundation (to R.A.K.), the Delaney AIDS Research Enterprise (AI096109 to S.G.D.), NIAID K24 (AI069994 to S.G.D.), the UCSF/Gladstone Institute of Virology & Immunology CFAR (P30 AI027763 to S.G.D.), and federal funds from the NCI (to F.M. and S.H.H.). Publisher Copyright: {\textcopyright} 2016",

year = "2016",

month = aug,

day = "11",

doi = "10.1016/j.cell.2016.06.039",

language = "English (US)",

volume = "166",

pages = "1004--1015",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "4",

}

TY - JOUR

T1 - Multiple Origins of Virus Persistence during Natural Control of HIV Infection

AU - Boritz, Eli A.

AU - Darko, Samuel

AU - Swaszek, Luke

AU - Wolf, Gideon

AU - Wells, David

AU - Wu, Xiaolin

AU - Henry, Amy R.

AU - Laboune, Farida

AU - Hu, Jianfei

AU - Ambrozak, David

AU - Hughes, Marybeth S.

AU - Hoh, Rebecca

AU - Casazza, Joseph P.

AU - Vostal, Alexander

AU - Bunis, Daniel

AU - Nganou-Makamdop, Krystelle

AU - Lee, James S.

AU - Migueles, Stephen A.

AU - Koup, Richard A.

AU - Connors, Mark

AU - Moir, Susan

AU - Schacker, Timothy

AU - Maldarelli, Frank

AU - Hughes, Stephen H.

AU - Deeks, Steven G.

AU - Douek, Daniel C.

N1 - Funding Information: We thank the study participants for their involvement in the study. We thank S. Kosakovsky-Pond for help with phylogenetic analysis and C. Petrovas for helpful discussions. D.C.D. and E.A.B. are funded by the NIH Intramural Research Program. D.C.D. is also funded by the NIAID Division of AIDS and the NIH Office of AIDS Research. Additional funding came from AIDS Vaccine Discovery grant OPP1032325 from the Bill and Melinda Gates Foundation (to R.A.K.), the Delaney AIDS Research Enterprise (AI096109 to S.G.D.), NIAID K24 (AI069994 to S.G.D.), the UCSF/Gladstone Institute of Virology & Immunology CFAR (P30 AI027763 to S.G.D.), and federal funds from the NCI (to F.M. and S.H.H.). Publisher Copyright: © 2016

PY - 2016/8/11

Y1 - 2016/8/11

N2 - 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 (TFH) cells and non-TFH 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.

AB - 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 (TFH) cells and non-TFH 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.

UR - http://www.scopus.com/inward/record.url?scp=84981318384&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84981318384&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2016.06.039

DO - 10.1016/j.cell.2016.06.039

M3 - Article

C2 - 27453467

AN - SCOPUS:84981318384

VL - 166

SP - 1004

EP - 1015

JO - Cell

JF - Cell

SN - 0092-8674

IS - 4

ER -

Multiple Origins of Virus Persistence during Natural Control of HIV Infection

Abstract

Bibliographical note

UN SDGs

Publisher link

Find It

Other files and links

Fingerprint

Cite this