Antiretroviral therapy reveals triphasic decay of intact SIV genomes and persistence of ancestral variants
Abstract
The decay kinetics of HIV-1-infected cells are critical to understand virus persistence. We evaluated the frequency of simian immunodeficiency virus (SIV)-infected cells for 4 years of antiretroviral therapy (ART). The intact proviral DNA assay (IPDA) and an assay for hypermutated proviruses revealed short- and long-term infected cell dynamics in macaques starting ART ~1 year after infection. Intact SIV genomes in circulating CD4+T cells showed triphasic decay with an initial phase slower than the decay of the plasma virus, a second phase faster than the second phase decay of intact HIV-1, and a stable third phase reached after 1.6–2.9 years. Hypermutated proviruses showed bi- or mono-phasic decay, reflecting different selective pressures. Viruses replicating at ART initiation had mutations conferring antibody escape. With time on ART, viruses with fewer mutations became more prominent, reflecting decay of variants replicating at ART initiation. Collectively, these findings confirm ART efficacy and indicate that cells enter the reservoir throughout untreated infection.
- Authors:
-
[2];
[2];
[2];
- Johns Hopkins Univ., Baltimore, MD (United States). School of Medicine
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
- Beth Israel Deaconess Medical Center, Boston, MA (United States)
- Wisconsin National Primate Research Center, Madison, WI (United States)
- Gilead Sciences, Foster City, CA (United States)
- Johns Hopkins Univ., Baltimore, MD (United States). School of Medicine; Howard Hughes Medical Inst., Baltimore, MD (United States)
- Publication Date:
- Research Org.:
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
- Sponsoring Org.:
- National Institutes of Health (NIH), National Institute of Dental and Craniofacial Research (NIDCR); USDOE National Nuclear Security Administration (NNSA)
- OSTI Identifier:
- 1963653
- Report Number(s):
- LA-UR-22-30227
Journal ID: ISSN 1931-3128
- Grant/Contract Number:
- 89233218CNA000001; UM1AI164556; R01- AI028433; R01-OD011095; P01-AI131365; R01-AI15270301; UM1-AI164561
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Cell Host & Microbe
- Additional Journal Information:
- Journal Volume: 31; Journal Issue: 3; Journal ID: ISSN 1931-3128
- Publisher:
- Elsevier
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; biological science; SIV, non-human primates, latency; latent reservoir; decay; clonal expansion; defective provirus
Citation Formats
Fray, Emily J., Wu, Fengting, Simonetti, Francesco R., Zitzmann, Carolin, Sambaturu, Narmada, Molina-Paris, Carmen, Bender, Alexandra M., Liu, Po-Ting, Ventura, John D., Wiseman, Roger W., O’Connor, David H., Geleziunas, Romas, Leitner, Thomas Kenneth, Ribeiro, Ruy Miguel, Perelson, Alan S., Barouch, Dan H., Siliciano, Janet D., and Siliciano, Robert F. Antiretroviral therapy reveals triphasic decay of intact SIV genomes and persistence of ancestral variants. United States: N. p., 2023.
Web. doi:10.1016/j.chom.2023.01.016.
Fray, Emily J., Wu, Fengting, Simonetti, Francesco R., Zitzmann, Carolin, Sambaturu, Narmada, Molina-Paris, Carmen, Bender, Alexandra M., Liu, Po-Ting, Ventura, John D., Wiseman, Roger W., O’Connor, David H., Geleziunas, Romas, Leitner, Thomas Kenneth, Ribeiro, Ruy Miguel, Perelson, Alan S., Barouch, Dan H., Siliciano, Janet D., & Siliciano, Robert F. Antiretroviral therapy reveals triphasic decay of intact SIV genomes and persistence of ancestral variants. United States. https://doi.org/10.1016/j.chom.2023.01.016
Fray, Emily J., Wu, Fengting, Simonetti, Francesco R., Zitzmann, Carolin, Sambaturu, Narmada, Molina-Paris, Carmen, Bender, Alexandra M., Liu, Po-Ting, Ventura, John D., Wiseman, Roger W., O’Connor, David H., Geleziunas, Romas, Leitner, Thomas Kenneth, Ribeiro, Ruy Miguel, Perelson, Alan S., Barouch, Dan H., Siliciano, Janet D., and Siliciano, Robert F. Wed .
"Antiretroviral therapy reveals triphasic decay of intact SIV genomes and persistence of ancestral variants". United States. https://doi.org/10.1016/j.chom.2023.01.016. https://www.osti.gov/servlets/purl/1963653.
@article{osti_1963653,
title = {Antiretroviral therapy reveals triphasic decay of intact SIV genomes and persistence of ancestral variants},
author = {Fray, Emily J. and Wu, Fengting and Simonetti, Francesco R. and Zitzmann, Carolin and Sambaturu, Narmada and Molina-Paris, Carmen and Bender, Alexandra M. and Liu, Po-Ting and Ventura, John D. and Wiseman, Roger W. and O’Connor, David H. and Geleziunas, Romas and Leitner, Thomas Kenneth and Ribeiro, Ruy Miguel and Perelson, Alan S. and Barouch, Dan H. and Siliciano, Janet D. and Siliciano, Robert F.},
abstractNote = {The decay kinetics of HIV-1-infected cells are critical to understand virus persistence. We evaluated the frequency of simian immunodeficiency virus (SIV)-infected cells for 4 years of antiretroviral therapy (ART). The intact proviral DNA assay (IPDA) and an assay for hypermutated proviruses revealed short- and long-term infected cell dynamics in macaques starting ART ~1 year after infection. Intact SIV genomes in circulating CD4+T cells showed triphasic decay with an initial phase slower than the decay of the plasma virus, a second phase faster than the second phase decay of intact HIV-1, and a stable third phase reached after 1.6–2.9 years. Hypermutated proviruses showed bi- or mono-phasic decay, reflecting different selective pressures. Viruses replicating at ART initiation had mutations conferring antibody escape. With time on ART, viruses with fewer mutations became more prominent, reflecting decay of variants replicating at ART initiation. Collectively, these findings confirm ART efficacy and indicate that cells enter the reservoir throughout untreated infection.},
doi = {10.1016/j.chom.2023.01.016},
journal = {Cell Host & Microbe},
number = 3,
volume = 31,
place = {United States},
year = {Wed Mar 08 00:00:00 EST 2023},
month = {Wed Mar 08 00:00:00 EST 2023}
}
Free Publicly Available Full Text
Publisher's Version of Record
Other availability
Search WorldCat to find libraries that may hold this journal
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
Longitudinal Dynamics of Intact HIV Proviral DNA and Outgrowth Virus Frequencies in a Cohort of Individuals Receiving Antiretroviral Therapy
journal, November 2020
- Falcinelli, Shane D.; Kilpatrick, Kayla W.; Read, Jenna
- The Journal of Infectious Diseases, Vol. 224, Issue 1
Tracking the Emergence of Host-Specific Simian Immunodeficiency Virus
env
and
nef
Populations Reveals
nef
Early Adaptation and Convergent Evolution in Brain of Naturally Progressing Rhesus Macaques
journal, August 2015
- Lamers, Susanna L.; Nolan, David J.; Rife, Brittany D.
- Journal of Virology, Vol. 89, Issue 16
HIV-1 Integration Landscape during Latent and Active Infection
journal, January 2015
- Cohn, Lillian B.; Silva, Israel T.; Oliveira, Thiago Y.
- Cell, Vol. 160, Issue 3
Virion Envelope Content, Infectivity, and Neutralization Sensitivity of Simian Immunodeficiency Virus
journal, October 2005
- Yuste, Eloísa; Johnson, Welkin; Pavlakis, George N.
- Journal of Virology, Vol. 79, Issue 19
SIV envelope glycoprotein epitopes recognized by antibodies from infected or vaccinated rhesus macaques
journal, February 1993
- Torres, José V.; Anderson, David E.; Malley, Arthur
- Journal of Medical Primatology, Vol. 22, Issue 2-3
Human Immunodeficiency Virus cDNA Metabolism: Notable Stability of Two-Long Terminal Repeat Circles
journal, April 2002
- Butler, Scott L.; Johnson, Erik P.; Bushman, Frederic D.
- Journal of Virology, Vol. 76, Issue 8
Proliferation of cells with HIV integrated into cancer genes contributes to persistent infection
journal, July 2014
- Wagner, T. A.; McLaughlin, S.; Garg, K.
- Science, Vol. 345, Issue 6196
Parallel analysis of transcription, integration, and sequence of single HIV-1 proviruses
journal, January 2022
- Einkauf, Kevin B.; Osborn, Matthew R.; Gao, Ce
- Cell, Vol. 185, Issue 2
Resting CD4
+
T Lymphocytes but Not Thymocytes Provide a Latent Viral Reservoir in a Simian Immunodeficiency Virus-
Macaca nemestrina
Model of Human Immunodeficiency Virus Type 1-Infected Patients on Highly Active Antiretroviral Therapy
journal, April 2003
- Shen, Anding; Zink, M. Christine; Mankowski, Joseph L.
- Journal of Virology, Vol. 77, Issue 8
Precise Quantitation of the Latent HIV-1 Reservoir: Implications for Eradication Strategies
journal, April 2015
- Crooks, Amanda M.; Bateson, Rosalie; Cope, Anna B.
- Journal of Infectious Diseases, Vol. 212, Issue 9
In Vivo Evidence for Instability of Episomal Human Immunodeficiency Virus Type 1 cDNA
journal, April 2005
- Sharkey, Mark; Triques, Karine; Kuritzkes, Daniel R.
- Journal of Virology, Vol. 79, Issue 8
The replication-competent HIV-1 latent reservoir is primarily established near the time of therapy initiation
journal, October 2019
- Abrahams, Melissa-Rose; Joseph, Sarah B.; Garrett, Nigel
- Science Translational Medicine, Vol. 11, Issue 513
Potent Antibody-Mediated Neutralization and Evolution of Antigenic Escape Variants of Simian Immunodeficiency Virus Strain SIVmac239 In Vivo
journal, July 2008
- Sato, Shuji; Yuste, Eloisa; Lauer, William A.
- Journal of Virology, Vol. 82, Issue 19
Convergent evolution of SIV env after independent inoculation of rhesus macaques with infectious proviral DNA
journal, August 2003
- Buckley, Kathleen A.; Li, Pei-Lin; Khimani, Anis H.
- Virology, Vol. 312, Issue 2
Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection
journal, January 1995
- Ho, David D.; Neumann, Avidan U.; Perelson, Alan S.
- Nature, Vol. 373, Issue 6510
Proliferation of latently infected CD4 + T cells carrying replication-competent HIV-1: Potential role in latent reservoir dynamics
journal, March 2017
- Hosmane, Nina N.; Kwon, Kyungyoon J.; Bruner, Katherine M.
- The Journal of Experimental Medicine, Vol. 214, Issue 4
A Simpler and More Sensitive Single-Copy HIV-1 RNA Assay for Quantification of Persistent HIV-1 Viremia in Individuals on Suppressive Antiretroviral Therapy
journal, March 2019
- Tosiano, Melissa A.; Jacobs, Jana L.; Shutt, Kathleen A.
- Journal of Clinical Microbiology, Vol. 57, Issue 3
The SIV Envelope Glycoprotein, Viral Tropism, and Pathogenesis: Novel Insights from Nonhuman Primate Models of AIDS
journal, April 2018
- Swanstrom, Adrienne E.; Del Prete, Gregory Q.; Deleage, Claire
- Current HIV Research, Vol. 16, Issue 1
Decay characteristics of HIV-1-infected compartments during combination therapy
journal, May 1997
- Perelson, Alan S.; Essunger, Paulina; Cao, Yunzhen
- Nature, Vol. 387, Issue 6629
Selection of genetic variants of simian immunodeficiency virus in persistently infected rhesus monkeys
journal, April 1991
- Burns, D. P.; Desrosiers, R. C.
- Journal of Virology, Vol. 65, Issue 4
Large number of rebounding/founder HIV variants emerge from multifocal infection in lymphatic tissues after treatment interruption
journal, February 2015
- Rothenberger, Meghan K.; Keele, Brandon F.; Wietgrefe, Stephen W.
- Proceedings of the National Academy of Sciences, Vol. 112, Issue 10
Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection
journal, May 2008
- Keele, B. F.; Giorgi, E. E.; Salazar-Gonzalez, J. F.
- Proceedings of the National Academy of Sciences, Vol. 105, Issue 21
Major histocompatibility complex genotyping with massively parallel pyrosequencing
journal, October 2009
- Wiseman, Roger W.; Karl, Julie A.; Bimber, Benjamin N.
- Nature Medicine, Vol. 15, Issue 11
Rapid Inflammasome Activation following Mucosal SIV Infection of Rhesus Monkeys
journal, April 2016
- Barouch, Dan H.; Ghneim, Khader; Bosche, William J.
- Cell, Vol. 165, Issue 3
Initial increase in blood CD4+ lymphocytes after HIV antiretroviral therapy reflects redistribution from lymphoid tissues
journal, May 1999
- Bucy, R. Pat; Hockett, Richard D.; Derdeyn, Cynthia A.
- Journal of Clinical Investigation, Vol. 103, Issue 10
Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection
journal, March 2005
- Mattapallil, Joseph J.; Douek, Daniel C.; Hill, Brenna
- Nature, Vol. 434, Issue 7037
Sexual Transmission and Propagation of SIV and HIV in Resting and Activated CD4+ T Cells
journal, November 1999
- Zhang, Z.
- Science, Vol. 286, Issue 5443
A Limited Number of Simian Immunodeficiency Virus (SIV) env Variants Are Transmitted to Rhesus Macaques Vaginally Inoculated with SIVmac251
journal, May 2010
- Stone, Mars; Keele, Brandon F.; Ma, Zhong-Min
- Journal of Virology, Vol. 84, Issue 14
HIV-1 variants are archived throughout infection and persist in the reservoir
journal, June 2020
- Brooks, Kelsie; Jones, Bradley R.; Dilernia, Dario A.
- PLOS Pathogens, Vol. 16, Issue 6
Defective HIV-1 proviruses produce novel protein-coding RNA species in HIV-infected patients on combination antiretroviral therapy
journal, July 2016
- Imamichi, Hiromi; Dewar, Robin L.; Adelsberger, Joseph W.
- Proceedings of the National Academy of Sciences, Vol. 113, Issue 31
Origin of rebound virus in chronically SIV-infected Rhesus monkeys following treatment discontinuation
journal, October 2020
- Liu, Po-Ting; Keele, Brandon F.; Abbink, Peter
- Nature Communications, Vol. 11, Issue 1
Persistence of episomal HIV-1 infection intermediates in patients on highly active anti-retroviral therapy
journal, January 2000
- Sharkey, Mark E.; Teo, Ian; Greenough, Thomas
- Nature Medicine, Vol. 6, Issue 1
HIV-1 entry into quiescent primary lymphocytes: Molecular analysis reveals a labile, latent viral structure
journal, April 1990
- Zack, Jerome A.; Arrigo, Salvatore J.; Weitsman, Stacy R.
- Cell, Vol. 61, Issue 2
HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression
journal, December 1999
- Davey, R. T.; Bhat, N.; Yoder, C.
- Proceedings of the National Academy of Sciences, Vol. 96, Issue 26
Peak SIV replication in resting memory CD4+ T cells depletes gut lamina propria CD4+ T cells
journal, March 2005
- Li, Qingsheng; Duan, Lijie; Estes, Jacob D.
- Nature, Vol. 434, Issue 7037
Autologous Neutralizing Antibodies to the Transmitted/Founder Viruses Emerge Late after Simian Immunodeficiency Virus SIVmac251 Infection of Rhesus Monkeys
journal, March 2010
- Yeh, W. W.; Rahman, I.; Hraber, P.
- Journal of Virology, Vol. 84, Issue 12
Phylogenetic approach to recover integration dates of latent HIV sequences within-host
journal, September 2018
- Jones, Bradley R.; Kinloch, Natalie N.; Horacsek, Joshua
- Proceedings of the National Academy of Sciences, Vol. 115, Issue 38
Paired quantitative and qualitative assessment of the replication-competent HIV-1 reservoir and comparison with integrated proviral DNA
journal, November 2016
- Lorenzi, Julio C. C.; Cohen, Yehuda Z.; Cohn, Lillian B.
- Proceedings of the National Academy of Sciences, Vol. 113, Issue 49
Quiescent T Lymphocytes as an Inducible Virus Reservoir in HIV-1 Infection
journal, October 1991
- Bukrinsky, M. I.; Stanwick, T. L.; Dempsey, M. P.
- Science, Vol. 254, Issue 5030
Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein
journal, July 2002
- Sheehy, Ann M.; Gaddis, Nathan C.; Choi, Jonathan D.
- Nature, Vol. 418, Issue 6898
Cytomegalovirus-vaccine-induced unconventional T cell priming and control of SIV replication is conserved between primate species
journal, September 2022
- Malouli, Daniel; Gilbride, Roxanne M.; Wu, Helen L.
- Cell Host & Microbe, Vol. 30, Issue 9
Sequential Evolution and Escape from Neutralization of Simian Immunodeficiency Virus SIVsmE660 Clones in Rhesus Macaques
journal, August 2012
- Wu, Fan; Ourmanov, Ilnour; Kuwata, Takeo
- Journal of Virology, Vol. 86, Issue 16
Animal models to achieve an HIV cure
journal, July 2016
- Kumar, Nitasha; Chahroudi, Ann; Silvestri, Guido
- Current Opinion in HIV and AIDS, Vol. 11, Issue 4
Complex decay dynamics of HIV virions, intact and defective proviruses, and 2LTR circles following initiation of antiretroviral therapy
journal, February 2022
- White, Jennifer A.; Simonetti, Francesco R.; Beg, Subul
- Proceedings of the National Academy of Sciences, Vol. 119, Issue 6
Establishment and stability of the latent HIV-1 DNA reservoir
journal, November 2016
- Brodin, Johanna; Zanini, Fabio; Thebo, Lina
- eLife, Vol. 5
Evaluating Clonal Expansion of HIV-Infected Cells: Optimization of PCR Strategies to Predict Clonality
journal, August 2016
- Laskey, Sarah B.; Pohlmeyer, Christopher W.; Bruner, Katherine M.
- PLOS Pathogens, Vol. 12, Issue 8
Early antiretroviral therapy limits SIV reservoir establishment to delay or prevent post-treatment viral rebound
journal, August 2018
- Okoye, Afam A.; Hansen, Scott G.; Vaidya, Mukta
- Nature Medicine, Vol. 24, Issue 9
Dynamics of HIV DNA reservoir seeding in a cohort of superinfected Kenyan women
journal, February 2020
- Pankau, Mark D.; Reeves, Daniel B.; Harkins, Elias
- PLOS Pathogens, Vol. 16, Issue 2
Clonal expansion of genome-intact HIV-1 in functionally polarized Th1 CD4+ T cells
journal, June 2017
- Lee, Guinevere Q.; Orlova-Fink, Nina; Einkauf, Kevin
- Journal of Clinical Investigation, Vol. 127, Issue 7
DNA Deamination Mediates Innate Immunity to Retroviral Infection
journal, June 2003
- Harris, Reuben S.; Bishop, Kate N.; Sheehy, Ann M.
- Cell, Vol. 113, Issue 6
HIV rebounds from latently infected cells, rather than from continuing low-level replication
journal, October 2008
- Joos, B.; Fischer, M.; Kuster, H.
- Proceedings of the National Academy of Sciences, Vol. 105, Issue 43
Short Communication: Comparative Evaluation of Coformulated Injectable Combination Antiretroviral Therapy Regimens in Simian Immunodeficiency Virus-Infected Rhesus Macaques
journal, February 2016
- Del Prete, Gregory Q.; Smedley, Jeremy; Macallister, Rhonda
- AIDS Research and Human Retroviruses, Vol. 32, Issue 2
Combined HIV-1 sequence and integration site analysis informs viral dynamics and allows reconstruction of replicating viral ancestors
journal, November 2019
- Patro, Sean C.; Brandt, Leah D.; Bale, Michael J.
- Proceedings of the National Academy of Sciences, Vol. 116, Issue 51
Clonal expansion of SIV-infected cells in macaques on antiretroviral therapy is similar to that of HIV-infected cells in humans
journal, July 2019
- Ferris, Andrea L.; Wells, David W.; Guo, Shuang
- PLOS Pathogens, Vol. 15, Issue 7
Rapid Loss of CD4 T Cells by Pyroptosis during Acute SIV Infection in Rhesus Macaques
journal, September 2022
- He, Xuan; Aid, Malika; Ventura, John D.
- Journal of Virology, Vol. 96, Issue 17
Replication-Competent Noninduced Proviruses in the Latent Reservoir Increase Barrier to HIV-1 Cure
journal, October 2013
- Ho, Ya-Chi; Shan, Liang; Hosmane, Nina N.
- Cell, Vol. 155, Issue 3
Kinetics of Human Immunodeficiency Virus Type 1 Decay following Entry into Resting CD4+ T Cells
journal, January 2005
- Zhou, Y.; Zhang, H.; Siliciano, J. D.
- Journal of Virology, Vol. 79, Issue 4
HIV-1 Dynamics in Vivo: Virion Clearance Rate, Infected Cell Life-Span, and Viral Generation Time
journal, March 1996
- Perelson, A. S.; Neumann, A. U.; Markowitz, M.
- Science, Vol. 271, Issue 5255
MEGA11: Molecular Evolutionary Genetics Analysis Version 11
journal, April 2021
- Tamura, Koichiro; Stecher, Glen; Kumar, Sudhir
- Molecular Biology and Evolution, Vol. 38, Issue 7
Accumulation of defective viral genomes in peripheral blood mononuclear cells of human immunodeficiency virus type 1-infected individuals
journal, March 1997
- Sanchez, G.; Xu, X.; Chermann, J. C.
- Journal of Virology, Vol. 71, Issue 3
Rapid Viral Decay in Simian Immunodeficiency Virus-Infected Macaques Receiving Quadruple Antiretroviral Therapy
journal, September 2006
- Brandin, E.; Thorstensson, R.; Bonhoeffer, S.
- Journal of Virology, Vol. 80, Issue 19
Envelope Variable Region 4 Is the First Target of Neutralizing Antibodies in Early Simian Immunodeficiency Virus mac251 Infection of Rhesus Monkeys
journal, July 2012
- Yeh, Wendy W.; Brassard, Laura M.; Miller, Caroline A.
- Journal of Virology, Vol. 86, Issue 13
Low-dose rectal inoculation of rhesus macaques by SIVsmE660 or SIVmac251 recapitulates human mucosal infection by HIV-1
journal, May 2009
- Keele, Brandon F.; Li, Hui; Learn, Gerald H.
- The Journal of Experimental Medicine, Vol. 206, Issue 5
The Landscape of Persistent Viral Genomes in ART-Treated SIV, SHIV, and HIV-2 Infections
journal, July 2019
- Bender, Alexandra M.; Simonetti, Francesco R.; Kumar, Mithra R.
- Cell Host & Microbe, Vol. 26, Issue 1
Consistent Viral Evolutionary Changes Associated with the Progression of Human Immunodeficiency Virus Type 1 Infection
journal, December 1999
- Shankarappa, Raj; Margolick, Joseph B.; Gange, Stephen J.
- Journal of Virology, Vol. 73, Issue 12
Role of CD8+ Lymphocytes in Control of Simian Immunodeficiency Virus Infection and Resistance to Rechallenge after Transient Early Antiretroviral Treatment
journal, November 2001
- Lifson, J. D.; Rossio, J. L.; Piatak, M.
- Journal of Virology, Vol. 75, Issue 21
Effects of natural sequence variation on recognition by monoclonal antibodies neutralize simian immunodeficiency virus infectivity
journal, September 1994
- Choi, W. S.; Collignon, C.; Thiriart, C.
- Journal of Virology, Vol. 68, Issue 9
Extensive envelope heterogeneity of simian immunodeficiency virus in tissues from infected macaques
journal, May 1994
- Campbell, B. J.; Hirsch, V. M.
- Journal of Virology, Vol. 68, Issue 5
Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy
journal, November 1997
- Chun, T. -W.; Stuyver, L.; Mizell, S. B.
- Proceedings of the National Academy of Sciences, Vol. 94, Issue 24
Detecting hypermutations in viral sequences with an emphasis on G -> A hypermutation
journal, April 2000
- Rose, P. P.; Korber, B. T.
- Bioinformatics, Vol. 16, Issue 4
Antigenic Variation of SIV: Mutations in V4 Alter the Neutralization Profile
journal, July 1996
- Kinsey, Nicole E.; Anderson, Mark G.; Unangst, Tami J.
- Virology, Vol. 221, Issue 1
Variation in simian immunodeficiency virus env is confined to V1 and V4 during progression to simian AIDS
journal, December 1991
- Overbaugh, J.; Rudensey, L. M.; Papenhausen, M. D.
- Journal of Virology, Vol. 65, Issue 12
Identification of Genetically Intact HIV-1 Proviruses in Specific CD4 + T Cells from Effectively Treated Participants
journal, October 2017
- Hiener, Bonnie; Horsburgh, Bethany A.; Eden, John-Sebastian
- Cell Reports, Vol. 21, Issue 3
A quantitative approach for measuring the reservoir of latent HIV-1 proviruses
journal, January 2019
- Bruner, Katherine M.; Wang, Zheng; Simonetti, Francesco R.
- Nature, Vol. 566, Issue 7742
A Simian Immunodeficiency Virus-Infected Macaque Model To Study Viral Reservoirs That Persist during Highly Active Antiretroviral Therapy
journal, July 2009
- Dinoso, J. B.; Rabi, S. A.; Blankson, J. N.
- Journal of Virology, Vol. 83, Issue 18
Biphasic kinetics of peripheral blood T cells after triple combination therapy in HIV-1 infection: A composite of redistribution and proliferation
journal, February 1998
- Pakker, Nadine G.; Notermans, Daan W.; De Boer, Rob J.
- Nature Medicine, Vol. 4, Issue 2
Rapid seeding of the viral reservoir prior to SIV viraemia in rhesus monkeys
journal, July 2014
- Whitney, James B.; Hill, Alison L.; Sanisetty, Srisowmya
- Nature, Vol. 512, Issue 7512
Proviruses with identical sequences comprise a large fraction of the replication-competent HIV reservoir
journal, March 2017
- Bui, John K.; Sobolewski, Michele D.; Keele, Brandon F.
- PLOS Pathogens, Vol. 13, Issue 3
Specific HIV integration sites are linked to clonal expansion and persistence of infected cells
journal, June 2014
- Maldarelli, F.; Wu, X.; Su, L.
- Science, Vol. 345, Issue 6193
Selective Decay of Intact HIV-1 Proviral DNA on Antiretroviral Therapy
journal, August 2020
- Gandhi, Rajesh T.; Cyktor, Joshua C.; Bosch, Ronald J.
- The Journal of Infectious Diseases, Vol. 223, Issue 2
Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells
journal, May 2003
- Siliciano, Janet D.; Kajdas, Joleen; Finzi, Diana
- Nature Medicine, Vol. 9, Issue 6
Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy
journal, May 1999
- Finzi, Diana; Blankson, Joel; Siliciano, Janet D.
- Nature Medicine, Vol. 5, Issue 5
Highly sensitive SIV plasma viral load assay: practical considerations, realistic performance expectations, and application to reverse engineering of vaccines for AIDS
journal, October 2005
- Nichole Cline, A.; Bess, Julian W.; Piatak, Michael Jr
- Journal of Medical Primatology, Vol. 34, Issue 5-6
Timing of the Components of the HIV Life Cycle in Productively Infected CD4+ T Cells in a Population of HIV-Infected Individuals
journal, August 2011
- Murray, J. M.; Kelleher, A. D.; Cooper, D. A.
- Journal of Virology, Vol. 85, Issue 20
Gastrointestinal Tract as a Major Site of CD4+ T Cell Depletion and Viral Replication in SIV Infection
journal, April 1998
- Veazey, R. S.
- Science, Vol. 280, Issue 5362
Differential decay of intact and defective proviral DNA in HIV-1–infected individuals on suppressive antiretroviral therapy
journal, February 2020
- Peluso, Michael J.; Bacchetti, Peter; Ritter, Kristen D.
- JCI Insight, Vol. 5, Issue 4
Dynamics of Simian Immunodeficiency Virus Two-Long-Terminal-Repeat Circles in the Presence and Absence of CD8 + Cells
journal, April 2018
- Policicchio, Benjamin B.; Cardozo, Erwing Fabian; Sette, Paola
- Journal of Virology, Vol. 92, Issue 13
Intrinsic Stability of Episomal Circles Formed during Human Immunodeficiency Virus Type 1 Replication
journal, April 2002
- Pierson, T. C.; Kieffer, T. L.; Ruff, C. T.
- Journal of Virology, Vol. 76, Issue 8
Viral dynamics in human immunodeficiency virus type 1 infection
journal, January 1995
- Wei, Xiping; Ghosh, Sajal K.; Taylor, Maria E.
- Nature, Vol. 373, Issue 6510
A Period of Transient Viremia and Occult Infection Precedes Persistent Viremia and Antiviral Immune Responses during Multiple Low-Dose Intravaginal Simian Immunodeficiency Virus Inoculations
journal, December 2004
- Ma, Zhong-Min; Abel, Kristina; Rourke, Tracy
- Journal of Virology, Vol. 78, Issue 24
Recovery of Replication-Competent HIV Despite Prolonged Suppression of Plasma Viremia
journal, November 1997
- Wong, J. K.
- Science, Vol. 278, Issue 5341
Defective proviruses rapidly accumulate during acute HIV-1 infection
journal, August 2016
- Bruner, Katherine M.; Murray, Alexandra J.; Pollack, Ross A.
- Nature Medicine, Vol. 22, Issue 9
Molecular Characterization of Preintegration Latency in Human Immunodeficiency Virus Type 1 Infection
journal, September 2002
- Pierson, T. C.; Zhou, Y.; Kieffer, T. L.
- Journal of Virology, Vol. 76, Issue 17
Comparative Characterization of Transfection- and Infection-Derived Simian Immunodeficiency Virus Challenge Stocks for In Vivo Nonhuman Primate Studies
journal, February 2013
- Del Prete, G. Q.; Scarlotta, M.; Newman, L.
- Journal of Virology, Vol. 87, Issue 8