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

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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

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Publisher Copyright:
© 2016

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

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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

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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.}",

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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.

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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.

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Multiple Origins of Virus Persistence during Natural Control of HIV Infection

Abstract

Bibliographical note

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