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Characterization of Intact Proviruses in Blood and Lymph Node from HIV-Infected Individuals Undergoing Analytical Treatment Interruption

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Vibholm, LK, Lorenzi, JCC, Pai, JA, Cohen, YZ, Oliveira, TY, Barton, JP, Garcia Noceda, M, Lu, C-L, Ablanedo-Terrazas, Y, Del Rio Estrada, PM, Reyes-Teran, G, Tolstrup, M, Denton, PW, Damsgaard, T, Søgaard, OS & Nussenzweig, MC 2019, 'Characterization of Intact Proviruses in Blood and Lymph Node from HIV-Infected Individuals Undergoing Analytical Treatment Interruption' Journal of Virology, bind 93, nr. 8. https://doi.org/10.1128/JVI.01920-18

APA

Vibholm, L. K., Lorenzi, J. C. C., Pai, J. A., Cohen, Y. Z., Oliveira, T. Y., Barton, J. P., ... Nussenzweig, M. C. (2019). Characterization of Intact Proviruses in Blood and Lymph Node from HIV-Infected Individuals Undergoing Analytical Treatment Interruption. Journal of Virology, 93(8). https://doi.org/10.1128/JVI.01920-18

CBE

Vibholm LK, Lorenzi JCC, Pai JA, Cohen YZ, Oliveira TY, Barton JP, Garcia Noceda M, Lu C-L, Ablanedo-Terrazas Y, Del Rio Estrada PM, Reyes-Teran G, Tolstrup M, Denton PW, Damsgaard T, Søgaard OS, Nussenzweig MC. 2019. Characterization of Intact Proviruses in Blood and Lymph Node from HIV-Infected Individuals Undergoing Analytical Treatment Interruption. Journal of Virology. 93(8). https://doi.org/10.1128/JVI.01920-18

MLA

Vancouver

Author

Vibholm, Line K ; Lorenzi, Julio C C ; Pai, Joy A ; Cohen, Yehuda Z ; Oliveira, Thiago Y ; Barton, John P ; Garcia Noceda, Marco ; Lu, Ching-Lan ; Ablanedo-Terrazas, Yuria ; Del Rio Estrada, Perla M ; Reyes-Teran, Gustavo ; Tolstrup, Martin ; Denton, Paul W ; Damsgaard, Tine ; Søgaard, Ole S ; Nussenzweig, Michel C. / Characterization of Intact Proviruses in Blood and Lymph Node from HIV-Infected Individuals Undergoing Analytical Treatment Interruption. I: Journal of Virology. 2019 ; Bind 93, Nr. 8.

Bibtex

@article{0173bda9658c43979efc1fa14821400f,
title = "Characterization of Intact Proviruses in Blood and Lymph Node from HIV-Infected Individuals Undergoing Analytical Treatment Interruption",
abstract = "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.",
keywords = "Adult, Anti-Retroviral Agents/administration & dosage, CD4-Positive T-Lymphocytes/metabolism, DNA, Viral/blood, Female, HIV Infections/blood, HIV-1/metabolism, Humans, Lymph Nodes/metabolism, Male, Middle Aged, Proviruses/metabolism, Toll-Like Receptor 9/agonists",
author = "Vibholm, {Line K} and Lorenzi, {Julio C C} and Pai, {Joy A} and Cohen, {Yehuda Z} and Oliveira, {Thiago Y} and Barton, {John P} and {Garcia Noceda}, Marco and Ching-Lan Lu and Yuria Ablanedo-Terrazas and {Del Rio Estrada}, {Perla M} and Gustavo Reyes-Teran and Martin Tolstrup and Denton, {Paul W} and Tine Damsgaard and S{\o}gaard, {Ole S} and Nussenzweig, {Michel C}",
note = "Copyright {\circledC} 2019 Vibholm et al.",
year = "2019",
month = "4",
day = "15",
doi = "10.1128/JVI.01920-18",
language = "English",
volume = "93",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "8",

}

RIS

TY - JOUR

T1 - Characterization of Intact Proviruses in Blood and Lymph Node from HIV-Infected Individuals Undergoing Analytical Treatment Interruption

AU - Vibholm, Line K

AU - Lorenzi, Julio C C

AU - Pai, Joy A

AU - Cohen, Yehuda Z

AU - Oliveira, Thiago Y

AU - Barton, John P

AU - Garcia Noceda, Marco

AU - Lu, Ching-Lan

AU - Ablanedo-Terrazas, Yuria

AU - Del Rio Estrada, Perla M

AU - Reyes-Teran, Gustavo

AU - Tolstrup, Martin

AU - Denton, Paul W

AU - Damsgaard, Tine

AU - Søgaard, Ole S

AU - Nussenzweig, Michel C

N1 - Copyright © 2019 Vibholm et al.

PY - 2019/4/15

Y1 - 2019/4/15

N2 - 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.

AB - 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.

KW - Adult

KW - Anti-Retroviral Agents/administration & dosage

KW - CD4-Positive T-Lymphocytes/metabolism

KW - DNA, Viral/blood

KW - Female

KW - HIV Infections/blood

KW - HIV-1/metabolism

KW - Humans

KW - Lymph Nodes/metabolism

KW - Male

KW - Middle Aged

KW - Proviruses/metabolism

KW - Toll-Like Receptor 9/agonists

U2 - 10.1128/JVI.01920-18

DO - 10.1128/JVI.01920-18

M3 - Journal article

VL - 93

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 8

ER -

ID: 59211623