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
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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