title: Current estimates for HIV-1 production imply rapid viral clearance in lymphoid tissues.
abstract: It has recently been estimated that a single HIV-1 infected cell produces between and more than viral particles over its life span. Since body-wide estimates of the ratio of free virus to productively infected cells are smaller than and much smaller than , 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.
authors.affiliation: Theoretical Biology and Bioinformatics, Utrecht University, Utrecht, The Netherlands. r.j.deboer@uu.nl
authors.forename: Rob J
authors.initials: RJ
authors.lastname: De Boer
authors.forename: Ruy M
authors.initials: RM
authors.lastname: Ribeiro
authors.forename: Alan S
authors.initials: AS
authors.lastname: Perelson
mesh_terms: D000818:Animals; D001781:Blood Component Removal; D003198:Computer Simulation; D020566:Dendritic Cells, Follicular / Q000276:immunology / Q000821:virology; D004195:Disease Models, Animal; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008221:Lymphoid Tissue / Q000276:immunology / Q000821:virology*; D008253:Macaca mulatta; D018448:Models, Immunological; D010949:Plasma / Q000821:virology; D012367:RNA, Viral / Q000032:analysis / Q000097:blood; D016097:Simian Acquired Immunodeficiency Syndrome / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000502:physiology; D014018:Tissue Distribution; D014771:Virion / Q000502:physiology
chemical_list: D012367:RNA, Viral
references.citation: Nature. 1995 Jan 12;373(6510):123-6
references.pmid: 7816094
references.citation: Nat Rev Immunol. 2005 Oct;5(10):783-92
references.pmid: 16200081
references.citation: AIDS. 2007 Jan 11;21(2):163-8
references.pmid: 17197806
references.citation: Math Biosci Eng. 2004 Sep;1(2):267-88
references.pmid: 20369971
references.citation: Nature. 1997 May 8;387(6629):183-8
references.pmid: 9144289
references.citation: Proc Natl Acad Sci U S A. 2007 Nov 27;104(48):19079-84
references.pmid: 18025463
references.citation: Proc Natl Acad Sci U S A. 1998 Feb 3;95(3):1154-9
references.pmid: 9448301
references.citation: J Infect Dis. 2000 Jan;181(1):354-7
references.pmid: 10608788
references.citation: J Virol. 2002 May;76(10):5271-3
references.pmid: 11967341
references.citation: Lancet. 1999 Nov 20;354(9192):1782-5
references.pmid: 10577640
references.citation: J Virol. 2001 Mar;75(6):2597-603
references.pmid: 11222682
references.citation: J Immunol. 2001 Jan 1;166(1):690-6
references.pmid: 11123354
references.citation: Virology. 1982 Jun;119(2):399-410
references.pmid: 6281982
references.citation: J Immunol. 2008 Aug 1;181(3):2065-70
references.pmid: 18641344
references.citation: J Gen Virol. 2005 Dec;86(Pt 12):3369-3373
references.pmid: 16298984
references.citation: J Virol. 1999 Jan;73(1):855-60
references.pmid: 9847402
references.citation: Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):10966-71
references.pmid: 10995459
references.citation: Nature. 1995 Jan 12;373(6510):117-22
references.pmid: 7529365
references.citation: Cell. 2000 Mar 3;100(5):587-97
references.pmid: 10721995
references.citation: Nature. 1997 May 8;387(6629):188-91
references.pmid: 9144290
references.citation: Science. 1996 Mar 15;271(5255):1582-6
references.pmid: 8599114
references.citation: Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):14681-6
references.pmid: 10611272
references.citation: Math Biosci. 2002 Apr;176(2):185-202
references.pmid: 11916508
references.citation: J Exp Med. 1999 May 17;189(10):1545-54
references.pmid: 10330433
references.citation: J Virol. 2003 Apr;77(8):5037-8
references.pmid: 12663814
references.citation: Cell Host Microbe. 2008 Jul 17;4(1):52-62
references.pmid: 18621010
references.citation: Biomed Pharmacother. 1998;52(10):436-9
references.pmid: 9921412
references.citation: J Virol. 2008 Jun;82(11):5548-61
references.pmid: 18385252
references.citation: Science. 1996 Nov 8;274(5289):985-9
references.pmid: 8875941