NIH VideoCast - Mechanisms of Virus Persistence in Blood and Tissue in HIV Controllers

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Mechanisms of Virus Persistence in Blood and Tissue in HIV Controllers

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Air date:	Wednesday, June 8, 2016, 4:15:00 PM Time displayed is Eastern Time, Washington DC Local
Views:	Total views: 427 (59 Live, 368 On-demand)
Category:	Immunology
Runtime:	00:50:19
Closed captioning:	Check box to display CC outside of the video Note: You can drag the captioning window around and resize it
Description:	Immunology Interest Group Dr. Douek is a Senior Investigator and the Chief of the Human Immunology Section of the Vaccine Research Center, NIAID / NIH. Dr. Douek studied medicine at the Universities of Oxford and London and then practiced internal medicine before pursuing a Ph.D. in Immunology at the University of London. Dr. Douek was appointed to the NIH Vaccine Research Center in November 2000. His laboratory, the Human Immunology Section, studies the processes that determine the course of human diseases in which the immune system, particularly its T cell arm, plays a central role in their pathogenesis and outcome. He aims to use the knowledge gained to initiate clinical studies of new therapeutic and vaccine approaches. Dr. Douek is a widely published author in the field of human immunology having made significant discoveries in thymic function, immune repertoire diversity, T-cell mediated immunity, mucosal immunology, innate immunity, hematopoietic progenitor cell transplantation. Currently, the main focus of his lab is both the pathogenesis and immune control of HIV infection. Dr. Douek sits on numerous scientific advisory boards and journal editorial boards. Dr. Douek was given the World AIDS Day Award in 2007, the NIH Director’s Award in 2008, and was recognized as one of the world’s top 50 scientists by Scientific American in 2005. He was named as one of the 2012 POZ 100 for his significant contributions to accelerating the end of AIDS. In 2014 he was named in the Thomson Reuters report entitled “The World’s Most Influential Scientific Minds”. 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.

NLM Title:	Mechanisms of virus persistence in blood and tissue in HIV controllers / Daniel Douek ; Immunology Interest Group.
Author:	Douek, Daniel. National Institutes of Health (U.S.). Immunology Interest Group,
Publisher:
Abstract:	(CIT): Immunology Interest Group. Dr. Douek is a Senior Investigator and the Chief of the Human Immunology Section of the Vaccine Research Center, NIAID / NIH. Dr. Douek studied medicine at the Universities of Oxford and London and then practiced internal medicine before pursuing a Ph.D. in Immunology at the University of London. Dr. Douek was appointed to the NIH Vaccine Research Center in November 2000. His laboratory, the Human Immunology Section, studies the processes that determine the course of human diseases in which the immune system, particularly its T cell arm, plays a central role in their pathogenesis and outcome. He aims to use the knowledge gained to initiate clinical studies of new therapeutic and vaccine approaches. Dr. Douek is a widely published author in the field of human immunology having made significant discoveries in thymic function, immune repertoire diversity, T-cell mediated immunity, mucosal immunology, innate immunity, hematopoietic progenitor cell transplantation. Currently, the main focus of his lab is both the pathogenesis and immune control of HIV infection. Dr. Douek sits on numerous scientific advisory boards and journal editorial boards. Dr. Douek was given the World AIDS Day Award in 2007, the NIH Director's Award in 2008, and was recognized as one of the world's top 50 scientists by Scientific American in 2005. He was named as one of the 2012 POZ 100 for his significant contributions to accelerating the end of AIDS. In 2014 he was named in the Thomson Reuters report entitled "The World's Most Influential Scientific Minds". 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.
Subjects:	HIV Infections--virology HIV--genetics Virus Replication--genetics
Publication Types:	Lecture Webcast

NLM Classification:	WC 503.3
NLM ID:	101686954
CIT Live ID:	19289
Permanent link:	https://videocast.nih.gov/watch=19289

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