Characterization of Intact Proviruses in Blood and Lymph Node from HIV-Infected Individuals Undergoing Analytical Treatment Interruption
Autor: | Perla M. Del Rio Estrada, Gustavo Reyes-Terán, John P. Barton, Line K. Vibholm, Joy A. Pai, Thiago Y. Oliveira, Yehuda Z. Cohen, Paul W. Denton, Martin Tolstrup, Ole Schmeltz Søgaard, Michel C. Nussenzweig, Tine Engberg Damsgaard, Yuria Ablanedo-Terrazas, Ching-Lan Lu, Marco Garcia Noceda, Julio C. C. Lorenzi |
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Přispěvatelé: | Silvestri, Guido |
Rok vydání: | 2019 |
Předmět: |
CD4-Positive T-Lymphocytes
Male viruses TISSUE RESERVOIRS HIV Infections infectious diseases Medical and Health Sciences ANTIRETROVIRAL THERAPY Proviruses Hiv infected 2.2 Factors relating to the physical environment 2.1 Biological and endogenous factors Viral Aetiology Lymph node 0303 health sciences Middle Aged lymph node Biological Sciences IMMUNIZATION 3. Good health AIDS medicine.anatomical_structure Lymphatic system Anti-Retroviral Agents HIV/AIDS TRIAL Female Lymph Infection Adult Immunology Viremia Biology Microbiology Virus 03 medical and health sciences LATENT RESERVOIR Virology medicine Humans 030304 developmental biology Agricultural and Veterinary Sciences business.industry 030306 microbiology PERSISTENCE TLR9 ATI DNA medicine.disease Antiretroviral therapy Peripheral blood recombination Good Health and Well Being Genetic Diversity and Evolution Treatment interruption Insect Science Toll-Like Receptor 9 CELLS REPLICATION DNA Viral HIV-1 Lymph Nodes business |
Zdroj: | Journal of virology, vol 93, iss 8 Journal of Virology Vibholm, L K, Lorenzi, J C C, Pai, J A, Cohen, Y Z, Oliveira, T Y, Barton, J P, Garcia Noceda, M, Lu, C L, Ablanedo-Terrazas, Y, Del Rio Estrada, P M, Reyes-Teran, G, Tolstrup, M, Denton, P W, Damsgaard, T, Søgaard, O S & Nussenzweig, M C 2019, ' Characterization of Intact Proviruses in Blood and Lymph Node from HIV-Infected Individuals Undergoing Analytical Treatment Interruption ', Journal of Virology, vol. 93, no. 8, e01920-18 . https://doi.org/10.1128/JVI.01920-18 |
Popis: | HIV-1 persists as a latent infection in CD4+ T cells that can be found in lymphoid tissues in infected individuals during ART. However, the importance of this tissue reservoir and its contribution to viral rebound upon ART interruption are not clear. In this study, we sought to compare latent HIV-1 from blood and lymph node CD4+ T cells from five HIV-1-infected individuals. Further, we analyzed the contribution of lymph node viruses to viral rebound. We observed that the frequencies of intact proviruses were the same in blood and lymph node. Moreover, expanded clones of T cells bearing identical proviruses were found in blood and lymph node. These latent reservoir sequences did not appear to be the direct origin of rebound virus. Instead, latent proviruses were found to contribute to the rebound compartment by recombination. The role of lymphoid tissue as a potential source of HIV-1 rebound following interruption of antiretroviral therapy (ART) is uncertain. To address this issue, we compared the latent viruses obtained from CD4+ T cells in peripheral blood and lymph nodes to viruses emerging during treatment interruption. Latent viruses were characterized by sequencing near-full-length (NFL) proviral DNA and env from viral outgrowth assays (VOAs). Five HIV-1-infected individuals on ART were studied, four of whom participated in a clinical trial of a TLR9 agonist that included an analytical treatment interruption. We found that 98% of intact or replication-competent clonal sequences overlapped between blood and lymph node. In contrast, there was no overlap between 205 latent reservoir and 125 rebound sequences in the four individuals who underwent treatment interruption. However, rebound viruses could be accounted for by recombination. The data suggest that CD4+ T cells carrying latent viruses circulate between blood and lymphoid tissues in individuals on ART and support the idea that recombination may play a role in the emergence of rebound viremia. IMPORTANCE HIV-1 persists as a latent infection in CD4+ T cells that can be found in lymphoid tissues in infected individuals during ART. However, the importance of this tissue reservoir and its contribution to viral rebound upon ART interruption are not clear. In this study, we sought to compare latent HIV-1 from blood and lymph node CD4+ T cells from five HIV-1-infected individuals. Further, we analyzed the contribution of lymph node viruses to viral rebound. We observed that the frequencies of intact proviruses were the same in blood and lymph node. Moreover, expanded clones of T cells bearing identical proviruses were found in blood and lymph node. These latent reservoir sequences did not appear to be the direct origin of rebound virus. Instead, latent proviruses were found to contribute to the rebound compartment by recombination. |
Databáze: | OpenAIRE |
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