Current Estimates for HIV-1 Production Imply Rapid Viral Clearance in Lymphoid Tissues

De Boer, Rob J.; Ribeiro, Ruy M.; Perelson, Alan S.

doi:10.1371/journal.pcbi.1000906

Current Estimates for HIV-1 Production Imply Rapid Viral Clearance in Lymphoid Tissues

Journal Article · Thu Sep 02 00:00:00 EDT 2010 · PLoS Computational Biology (Online)

DOI:https://doi.org/10.1371/journal.pcbi.1000906· OSTI ID:1627203

De Boer, Rob J. ^[1]; Ribeiro, Ruy M. ^[2]; Perelson, Alan S. ^[2]

Univ. of Utrecht (Netherlands). Theoretical Biology and Bioinformatics; DOE/OSTI
Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Biology and Biphysics

It has recently been estimated that a single HIV-1 infected cell produces between 103 and more than 104 viral particles over its life span. Since body-wide estimates of the ratio of free virus to productively infected cells are smaller than 103 and much smaller than 104, individual virions must be cleared rapidly. This seems difficult to reconcile with the fact that most of the total body virus is trapped on follicular dendritic cells where it can survive for many months. It has also been difficult to reconcile the vast difference in the rates at which the virus is cleared from the blood in rhesus macaques and in chronically infected patients. Here we attempt to reconcile these seemingly contradictory observations by considering the virion clearance rate in various organs and the virion exchange rates between them. The main results are that the per capita clearance rate of free virus in lymphoid tissue should be fast, the virion exchange rate between lymphoid tissue and the blood should be slow, and the comparatively slow previous estimates for the virion clearance rate from the blood correspond to the rate of virion efflux from the blood to other organs where the virus is ultimately cleared.

View Accepted Manuscript (DOE)

Research Organization:: Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

Grant/Contract Number:: AC52-06NA25396

OSTI ID:: 1627203

Journal Information:: PLoS Computational Biology (Online), Journal Name: PLoS Computational Biology (Online) Journal Issue: 9 Vol. 6; ISSN 1553-7358

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

References (37)

Visna DNA synthesis and the tempo of infection in vitro Haase, A. T.; Stowring, L.; Harris, J. D. Virology, Vol. 119, Issue 2 https://doi.org/10.1016/0042-6822(82)90099-x	journal	June 1982
Retention of antigen on follicular dendritic cells and B lymphocytes through complement-mediated multivalent ligand–receptor interactions: theory and application to HIV treatment Hlavacek, William S.; Percus, Jerome K.; Percus, Ora E. Mathematical Biosciences, Vol. 176, Issue 2 https://doi.org/10.1016/s0025-5564(02)00091-3	journal	April 2002
Binding of HIV-1 to RBCs involves the Duffy Antigen Receptors for Chemokines (DARC) Lachgar, A.; Jaureguiberry, G.; Le Buenac, H. Biomedicine & Pharmacotherapy, Vol. 52, Issue 10 https://doi.org/10.1016/s0753-3322(99)80021-3	journal	December 1998
Perils at mucosal front lines for HIV and SIV and their hosts Haase, Ashley T. Nature Reviews Immunology, Vol. 5, Issue 10 https://doi.org/10.1038/nri1706	journal	October 2005
Influence of follicular dendritic cells on decay of HIV during antiretroviral therapy Hlavacek, W. S.; Stilianakis, N. I.; Notermans, D. W. Proceedings of the National Academy of Sciences, Vol. 97, Issue 20 https://doi.org/10.1073/pnas.190065897	journal	September 2000
Kinetics of CD4+ T cell repopulation of lymphoid tissues after treatment of HIV-1 infection Zhang, Z. -Q.; Notermans, D. W.; Sedgewick, G. Proceedings of the National Academy of Sciences, Vol. 95, Issue 3 https://doi.org/10.1073/pnas.95.3.1154	journal	February 1998
Dissociation of HIV-1 from follicular dendritic cells during HAART: Mathematical analysis Hlavacek, W. S.; Wofsy, C.; Perelson, A. S. Proceedings of the National Academy of Sciences, Vol. 96, Issue 26 https://doi.org/10.1073/pnas.96.26.14681	journal	December 1999
Constant Mean Viral Copy Number per Infected Cell in Tissues Regardless of High, Low, or Undetectable Plasma HIV RNA Hockett, Richard D.; Michael Kilby, J.; Derdeyn, Cynthia A. The Journal of Experimental Medicine, Vol. 189, Issue 10 https://doi.org/10.1084/jem.189.10.1545	journal	May 1999
Rapid Accumulation of Human Immunodeficiency Virus (HIV) in Lymphatic Tissue Reservoirs during Acute and Early HIV Infection: Implications for Timing of Antiretroviral Therapy Schacker, Timothy; Little, Susan; Connick, Elizabeth The Journal of Infectious Diseases, Vol. 181, Issue 1 https://doi.org/10.1086/315178	journal	January 2000
Determination of simian immunodeficiency virus production by infected activated and resting cells Reilly, Cavan; Wietgrefe, Steve; Sedgewick, Gerald AIDS, Vol. 21, Issue 2 https://doi.org/10.1097/qad.0b013e328012565b	journal	January 2007
The majority of human immunodeficiency virus type 1 particles present within splenic germinal centres are produced locally Dumaurier, Marie-Jeanne; Gratton, Sophie; Wain-Hobson, Simon Journal of General Virology, Vol. 86, Issue 12 https://doi.org/10.1099/vir.0.81133-0	journal	December 2005
HIV-1 Dynamics in Vivo: Virion Clearance Rate, Infected Cell Life-Span, and Viral Generation Time Perelson, A. S.; Neumann, A. U.; Markowitz, M. Science, Vol. 271, Issue 5255 https://doi.org/10.1126/science.271.5255.1582	journal	March 1996
Quantitative Image Analysis of HIV-1 Infection in Lymphoid Tissue Haase, Ashley T.; Henry, Keith; Zupancic, Mary Science, Vol. 274, Issue 5289 https://doi.org/10.1126/science.274.5289.985	journal	November 1996
Characterization of the Follicular Dendritic Cell Reservoir of Human Immunodeficiency Virus Type 1 Keele, Brandon F.; Tazi, Loubna; Gartner, Suzanne Journal of Virology, Vol. 82, Issue 11 https://doi.org/10.1128/jvi.00124-08	journal	April 2008
Rapid Clearance of Simian Immunodeficiency Virus Particles from Plasma of Rhesus Macaques Zhang, Linqi; Dailey, Peter J.; He, Tian Journal of Virology, Vol. 73, Issue 1 https://doi.org/10.1128/jvi.73.1.855-860.1999	journal	January 1999
Release of Virus from Lymphoid Tissue Affects Human Immunodeficiency Virus Type 1 and Hepatitis C Virus Kinetics in the Blood Müller, Viktor; Marée, Athanasius F. M.; De Boer, Rob J. Journal of Virology, Vol. 75, Issue 6 https://doi.org/10.1128/jvi.75.6.2597-2603.2001	journal	March 2001
The Liver Is a Major Organ for Clearing Simian Immunodeficiency Virus in Rhesus Monkeys Zhang, L.; Dailey, P. J.; Gettie, A. Journal of Virology, Vol. 76, Issue 10 https://doi.org/10.1128/jvi.76.10.5271-5273.2002	journal	May 2002
Persistence of Infectious HIV on Follicular Dendritic Cells Smith, Beverly A.; Gartner, Suzanne; Liu, Yiling The Journal of Immunology, Vol. 166, Issue 1 https://doi.org/10.4049/jimmunol.166.1.690	journal	January 2001
Visna DNA synthesis and the tempo of infection in vitro Haase, A. T.; Stowring, L.; Harris, J. D. Virology, Vol. 119, Issue 2 https://doi.org/10.1016/0042-6822(82)90099-X	journal	June 1982
Retention of antigen on follicular dendritic cells and B lymphocytes through complement-mediated multivalent ligand–receptor interactions: theory and application to HIV treatment Hlavacek, William S.; Percus, Jerome K.; Percus, Ora E. Mathematical Biosciences, Vol. 176, Issue 2 https://doi.org/10.1016/S0025-5564(02)00091-3	journal	April 2002
DC-SIGN, a Dendritic Cell–Specific HIV-1-Binding Protein that Enhances trans-Infection of T Cells Geijtenbeek, Teunis B. H.; Kwon, Douglas S.; Torensma, Ruurd Cell, Vol. 100, Issue 5 https://doi.org/10.1016/S0092-8674(00)80694-7	journal	March 2000
Rapid production and clearance of HIV-1 and hepatitis C virus assessed by large volume plasma apheresis Ramratnam, Bharat; Bonhoeffer, Sebastian; Binley, James The Lancet, Vol. 354, Issue 9192 https://doi.org/10.1016/S0140-6736(99)02035-8	journal	November 1999
Binding of HIV-1 to RBCs involves the Duffy Antigen Receptors for Chemokines (DARC) Lachgar, A.; Jaureguiberry, G.; Le Buenac, H. Biomedicine & Pharmacotherapy, Vol. 52, Issue 10 https://doi.org/10.1016/S0753-3322(99)80021-3	journal	December 1998
Duffy Antigen Receptor for Chemokines Mediates trans-Infection of HIV-1 from Red Blood Cells to Target Cells and Affects HIV-AIDS Susceptibility He, Weijing; Neil, Stuart; Kulkarni, Hemant Cell Host & Microbe, Vol. 4, Issue 1 https://doi.org/10.1016/j.chom.2008.06.002	journal	July 2008
Viral dynamics in human immunodeficiency virus type 1 infection Wei, Xiping; Ghosh, Sajal K.; Taylor, Maria E. Nature, Vol. 373, Issue 6510 https://doi.org/10.1038/373117a0	journal	January 1995
Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection Ho, David D.; Neumann, Avidan U.; Perelson, Alan S. Nature, Vol. 373, Issue 6510 https://doi.org/10.1038/373123a0	journal	January 1995
Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection Chun, Tae-Wook; Carruth, Lucy; Finzi, Diana Nature, Vol. 387, Issue 6629 https://doi.org/10.1038/387183a0	journal	May 1997
Decay characteristics of HIV-1-infected compartments during combination therapy Perelson, Alan S.; Essunger, Paulina; Cao, Yunzhen Nature, Vol. 387, Issue 6629 https://doi.org/10.1038/387188a0	journal	May 1997
Determination of virus burst size in vivo using a single-cycle SIV in rhesus macaques Chen, H. Y.; Di Mascio, M.; Perelson, A. S. Proceedings of the National Academy of Sciences, Vol. 104, Issue 48 https://doi.org/10.1073/pnas.0707449104	journal	November 2007
Determination of simian immunodeficiency virus production by infected activated and resting cells Reilly, Cavan; Wietgrefe, Steve; Sedgewick, Gerald AIDS, Vol. 21, Issue 2 https://doi.org/10.1097/QAD.0b013e328012565b	journal	January 2007
Characterization of the Follicular Dendritic Cell Reservoir of Human Immunodeficiency Virus Type 1 Keele, Brandon F.; Tazi, Loubna; Gartner, Suzanne Journal of Virology, Vol. 82, Issue 11 https://doi.org/10.1128/JVI.00124-08	journal	April 2008
Rapid Clearance of Simian Immunodeficiency Virus Particles from Plasma of Rhesus Macaques Zhang, Linqi; Dailey, Peter J.; He, Tian Journal of Virology, Vol. 73, Issue 1 https://doi.org/10.1128/JVI.73.1.855-860.1999	journal	January 1999
Release of Virus from Lymphoid Tissue Affects Human Immunodeficiency Virus Type 1 and Hepatitis C Virus Kinetics in the Blood Müller, Viktor; Marée, Athanasius F. M.; De Boer, Rob J. Journal of Virology, Vol. 75, Issue 6 https://doi.org/10.1128/JVI.75.6.2597-2603.2001	journal	March 2001
The Liver Is a Major Organ for Clearing Simian Immunodeficiency Virus in Rhesus Monkeys Zhang, L.; Dailey, P. J.; Gettie, A. Journal of Virology, Vol. 76, Issue 10 https://doi.org/10.1128/JVI.76.10.5271-5273.2002	journal	May 2002
A Novel Antiviral Intervention Results in More Accurate Assessment of Human Immunodeficiency Virus Type 1 Replication Dynamics and T-Cell Decay In Vivo Markowitz, M.; Louie, M.; Hurley, A. Journal of Virology, Vol. 77, Issue 8 https://doi.org/10.1128/JVI.77.8.5037-5038.2003	journal	April 2003
An Age-Structured Model of HIV Infection that Allows for Variations in the Production Rate of Viral Particles and the Death Rate of Productively Infected Cells Nelson, Patrick W.; Gilchrist, Michael A.; Coombs, Daniel Mathematical Biosciences and Engineering, Vol. 1, Issue 2 https://doi.org/10.3934/mbe.2004.1.267	journal	July 2004
HIV Envelope Binding by Macrophage-Expressed gp340 Promotes HIV-1 Infection Cannon, Georgetta; Yi, Yanjie; Ni, Houping The Journal of Immunology, Vol. 181, Issue 3 https://doi.org/10.4049/jimmunol.181.3.2065	journal	July 2008

Cited By (31)

Ad26/MVA therapeutic vaccination with TLR7 stimulation in SIV-infected rhesus monkeys Borducchi, Erica N.; Cabral, Crystal; Stephenson, Kathryn E. Nature, Vol. 540, Issue 7632 https://doi.org/10.1038/nature20583	journal	November 2016
Factors limiting the transmission of HIV mutations conferring drug resistance: fitness costs and genetic bottlenecks Wagner, Bradley G.; Garcia-Lerma, J. Gerardo; Blower, Sally Scientific Reports, Vol. 2, Issue 1 https://doi.org/10.1038/srep00320	journal	March 2012
Linking immunological and epidemiological dynamics of HIV: the case of super-infection Martcheva, Maia; Li, Xue-Zhi Journal of Biological Dynamics, Vol. 7, Issue 1 https://doi.org/10.1080/17513758.2013.820358	journal	December 2013
Notwithstanding Circumstantial Alibis, Cytotoxic T Cells Can Be Major Killers of HIV-1-Infected Cells Gadhamsetty, Saikrishna; Coorens, Tim; de Boer, Rob J. Journal of Virology, Vol. 90, Issue 16 https://doi.org/10.1128/jvi.00306-16	journal	May 2016
A hunter virus that targets both infected cells and HIV free virions: Implications for therapy Greer, Cody; García-Ramos, Gisela Theoretical Biology and Medical Modelling, Vol. 9, Issue 1 https://doi.org/10.1186/1742-4682-9-52	journal	December 2012
Immune Activation Promotes Evolutionary Conservation of T-Cell Epitopes in HIV-1 Sanjuán, Rafael; Nebot, Miguel R.; Peris, Joan B. PLoS Biology, Vol. 11, Issue 4 https://doi.org/10.1371/journal.pbio.1001523	journal	April 2013
Which of Our Modeling Predictions Are Robust? De Boer, Rob J. PLoS Computational Biology, Vol. 8, Issue 7 https://doi.org/10.1371/journal.pcbi.1002593	journal	July 2012
Quantifying the Turnover of Transcriptional Subclasses of HIV-1-Infected Cells Althaus, Christian L.; Joos, Beda; Perelson, Alan S. PLoS Computational Biology, Vol. 10, Issue 10 https://doi.org/10.1371/journal.pcbi.1003871	journal	October 2014
Residual Viremia in Treated HIV+ Individuals Conway, Jessica M.; Perelson, Alan S. PLOS Computational Biology, Vol. 12, Issue 1 https://doi.org/10.1371/journal.pcbi.1004677	journal	January 2016
Modelling HIV and MTB Co-Infection Including Combined Treatment Strategies Ramkissoon, Santosh; Mwambi, Henry G.; Matthews, Alan P. PLoS ONE, Vol. 7, Issue 11 https://doi.org/10.1371/journal.pone.0049492	journal	November 2012
Multi-dose Romidepsin Reactivates Replication Competent SIV in Post-antiretroviral Rhesus Macaque Controllers Policicchio, Benjamin B.; Xu, Cuiling; Brocca-Cofano, Egidio PLOS Pathogens, Vol. 12, Issue 9 https://doi.org/10.1371/journal.ppat.1005879	journal	September 2016
Are microRNAs Important Players in HIV-1 Infection? An Update Balasubramaniam, Muthukumar; Pandhare, Jui; Dash, Chandravanu Viruses, Vol. 10, Issue 3 https://doi.org/10.3390/v10030110	journal	March 2018
Modelling the Course of an HIV Infection: Insights from Ecology and Evolution Alizon, Samuel; Magnus, Carsten Viruses, Vol. 4, Issue 10 https://doi.org/10.3390/v4101984	journal	October 2012
Simple Mathematical Models Do Not Accurately Predict Early SIV Dynamics Noecker, Cecilia; Schaefer, Krista; Zaccheo, Kelly Viruses, Vol. 7, Issue 3 https://doi.org/10.3390/v7031189	journal	March 2015
The effect of interference on the CD8+ T cell escape rates in HIV Garcia, Victor; Regoes, Roland arXiv https://doi.org/10.48550/arxiv.1409.7774	preprint	January 2014
Dynamics of HIV infection in lymphoid tissue network Nakaoka, Shinji; Iwami, Shingo; Sato, Kei Journal of Mathematical Biology, Vol. 72, Issue 4 https://doi.org/10.1007/s00285-015-0940-x	journal	October 2015
Within-Host Viral Dynamics in a Multi-compartmental Environment Chen, Shyan-Shiou; Cheng, Chang-Yuan; Rong, Libin Bulletin of Mathematical Biology, Vol. 81, Issue 10 https://doi.org/10.1007/s11538-019-00658-1	journal	August 2019
Human Immunodeficiency Virus Infection : from Biological Observations to Mechanistic Mathematical Modelling Bocharov, G.; Chereshnev, V.; Gainova, I. Mathematical Modelling of Natural Phenomena, Vol. 7, Issue 5 https://doi.org/10.1051/mmnp/20127507	journal	January 2012
Stochastic effects are important in intrahost HIV evolution even when viral loads are high Read, E. L.; Tovo-Dwyer, A. A.; Chakraborty, A. K. Proceedings of the National Academy of Sciences, Vol. 109, Issue 48 https://doi.org/10.1073/pnas.1206940109	journal	October 2012
Impaired immune evasion in HIV through intracellular delays and multiple infection of cells Althaus, Christian L.; De Boer, Rob J. Proceedings of the Royal Society B: Biological Sciences, Vol. 279, Issue 1740 https://doi.org/10.1098/rspb.2012.0328	journal	April 2012
Identification of drug resistance mutations in HIV from constraints on natural evolution Butler, Thomas C.; Barton, John P.; Kardar, Mehran Physical Review E, Vol. 93, Issue 2 https://doi.org/10.1103/physreve.93.022412	journal	February 2016
Insight into treatment of HIV infection from viral dynamics models Hill, Alison L.; Rosenbloom, Daniel I. S.; Nowak, Martin A. Immunological Reviews, Vol. 285, Issue 1 https://doi.org/10.1111/imr.12698	journal	August 2018
Enhanced clearance of HIV-1-infected cells by broadly neutralizing antibodies against HIV-1 in vivo Lu, C. -L.; Murakowski, D. K.; Bournazos, S. Science, Vol. 352, Issue 6288 https://doi.org/10.1126/science.aaf1279	journal	May 2016
From Individual Health to Community Health: Towards Multiscale Modeling of Directly Transmitted Infectious Disease Systems Garira, Winston; Mafunda, Martin Canaan Journal of Biological Systems, Vol. 27, Issue 01 https://doi.org/10.1142/s0218339019500074	journal	March 2019
Gene activity in primary T cells infected with HIV89.6: intron retention and induction of genomic repeats Sherrill-Mix, Scott; Ocwieja, Karen E.; Bushman, Frederic D. Retrovirology, Vol. 12, Issue 1 https://doi.org/10.1186/s12977-015-0205-1	journal	September 2015
Large Variations in HIV-1 Viral Load Explained by Shifting-Mosaic Metapopulation Dynamics Lythgoe, Katrina A.; Blanquart, François; Pellis, Lorenzo PLOS Biology, Vol. 14, Issue 10 https://doi.org/10.1371/journal.pbio.1002567	journal	October 2016
Stochastic Theory of Early Viral Infection: Continuous versus Burst Production of Virions Pearson, John E.; Krapivsky, Paul; Perelson, Alan S. PLoS Computational Biology, Vol. 7, Issue 2 https://doi.org/10.1371/journal.pcbi.1001058	journal	February 2011
Gag-Pol Processing during HIV-1 Virion Maturation: A Systems Biology Approach Könnyű, Balázs; Sadiq, S. Kashif; Turányi, Tamás PLoS Computational Biology, Vol. 9, Issue 6 https://doi.org/10.1371/journal.pcbi.1003103	journal	June 2013
Hybrid Spreading Mechanisms and T Cell Activation Shape the Dynamics of HIV-1 Infection Zhang, Changwang; Zhou, Shi; Groppelli, Elisabetta PLOS Computational Biology, Vol. 11, Issue 4 https://doi.org/10.1371/journal.pcbi.1004179	journal	April 2015
Exploring an alternative explanation for the second phase of viral decay: Infection of short-lived cells in a drug-limited compartment during HAART Sanche, Steven; Mesplède, Thibault; Sheehan, Nancy L. PLOS ONE, Vol. 13, Issue 7 https://doi.org/10.1371/journal.pone.0198090	journal	July 2018
Identification of drug resistance mutations in HIV from constraints on natural evolution Butler, Thomas C.; Barton, John P.; Kardar, Mehran arXiv https://doi.org/10.48550/arxiv.1508.01469	text	January 2015

Similar Records

Quantitative image analysis of HIV-1 infection in lymphoid tissue

Journal Article · Thu Nov 07 23:00:00 EST 1996 · Science · OSTI ID:433222

Persistent Viral Reservoirs in Lymphoid Tissues in SIV-Infected Rhesus Macaques of Chinese-Origin on Suppressive Antiretroviral Therapy

Journal Article · Sat Jan 26 19:00:00 EST 2019 · Viruses · OSTI ID:1628585

Induction of potent local cellular immunity with low dose X4 SHIV{sub SF33A} vaginal exposure

Journal Article · Wed Oct 10 00:00:00 EDT 2007 · Virology · OSTI ID:21077981

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Biochemistry & Molecular Biology
Mathematical & Computational Biology

Current Estimates for HIV-1 Production Imply Rapid Viral Clearance in Lymphoid Tissues

Citation Formats

References (37)

Cited By (31)

Similar Records

Related Subjects