Pathogenesis of HIV infection: what the virus spares is as important as what it destroys

Nature Medicine
Zvi GrossmanLouis J Picker

Abstract

Upon transmission to a new host, HIV targets CCR5+ CD4+ effector memory T cells, resulting in acute, massive depletion of these cells from mucosal effector sites. This depletion does not initially compromise the regenerative capacity of the immune system because naive and most central memory T cells are spared. Here, we discuss evidence suggesting that frequent activation of these spared cells during the chronic phase of HIV infection supplies mucosal tissues with short-lived CCR5+ CD4+ effector cells that prevent life-threatening infections. This immune activation also facilitates continued viral replication, but infection and killing of target T cells by HIV are selective and the impact on effector-cell lifespan is limited. We propose, however, that persistent activation progressively disrupts the functional organization of the immune system, reducing its regenerative capacity and facilitating viral evolution that leads to loss of the exquisite target cell-sparing selectivity of viral replication, ultimately resulting in AIDS.

References

Nov 1, 1993·Clinical Immunology and Immunopathology·Z GrossmanR B Herberman
Apr 1, 1993·Journal of Virology·D S DimitrovM A Martin
Sep 1, 1996·The Journal of Infection·M R Evans, M H Wansbrough-Jones
Apr 1, 1997·Immunological Reviews·A M Mowat, J L Viney
Feb 24, 1998·Clinical and Experimental Immunology·Z BentwichZ Grossman
Mar 12, 1998·Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology : Official Publication of the International Retrovirology Association·R W AndersonH W Sheppard
May 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·Z GrossmanW E Paul
Jun 17, 1998·The Journal of Clinical Investigation·J M McCuneR M Grant
Aug 15, 1998·Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology : Official Publication of the International Retrovirology Association·Z LiuJ V Giorgi
Apr 15, 1999·Immunology Letters·B AutranP Debré
May 14, 1999·Current Opinion in Immunology·A A Freitas, B Rocha
Sep 28, 1999·The Journal of Experimental Medicine·S J LittleD V Havlir
Mar 11, 2000·The Journal of Clinical Investigation·J M McCuneM Hellerstein
Jun 3, 2000·Annual Review of Immunology·A A Freitas, B Rocha
Mar 23, 2001·Nature Immunology·M D HazenbergF Miedema
Nov 30, 2000·Proceedings of the National Academy of Sciences of the United States of America·R A LempickiH C Lane
Dec 15, 2000·Journal of Acquired Immune Deficiency Syndromes : JAIDS·J W Cohen StuartR J de Boer
Dec 20, 2000·Proceedings of the National Academy of Sciences of the United States of America·S GrattonS Wain-Hobson
Jan 6, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·J J CampbellL Wu
Mar 13, 2001·Annual Review of Immunology·M K JenkinsK A Pape
Mar 15, 2001·Nature Immunology·P MarrackJ Kappler
Dec 26, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·Christine J PitcherLouis J Picker
Jan 12, 2002·The American Journal of Pathology·Eric J KunkelJames J Campbell
Mar 5, 2002·Nature Medicine·Mark B Feinberg, John P Moore
Apr 3, 2002·Nature Medicine·Zvi GrossmanWilliam E Paul

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Citations

May 27, 2008·Cellular and Molecular Life Sciences : CMLS·H Garg, R Blumenthal
Jul 15, 2011·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Xu WangWen-Zhe Ho
Mar 7, 2007·Current HIV/AIDS Reports·Satya Dandekar
Mar 7, 2007·Current HIV/AIDS Reports·Peter W Hunt
Jan 20, 2009·Current HIV/AIDS Reports·Andrea LiscoLeonid Margolis
Apr 16, 2009·Current Infectious Disease Reports·Alexandra M Ortiz, Guido Silvestri
Oct 28, 2009·Immunology and Cell Biology·Susan Moir, Anthony S Fauci
Nov 21, 2007·Nature Medicine·Pisana Moroni RawsonVincenzo Barnaba
Mar 26, 2009·Nature Reviews. Immunology·Susan Moir, Anthony S Fauci
Apr 8, 2010·Nature Reviews. Microbiology·Mélanie LambotinHeidi Barth
Feb 1, 2008·Proceedings of the National Academy of Sciences of the United States of America·Vincent VieillardPatrice Debré
Aug 12, 2009·Proceedings of the National Academy of Sciences of the United States of America·Rui WangDerya Unutmaz
Dec 1, 2010·The Journal of Experimental Medicine·Christof GeldmacherRichard A Koup
Feb 5, 2008·The Journal of Infectious Diseases·Susan MoirAnthony S Fauci
May 14, 2008·The Journal of Infectious Diseases·UNKNOWN Strategies for Management of Antiretroviral Therapy (SMART) Study GroupAndrew N Phillips
Nov 13, 2008·The Journal of Infectious Diseases·Christof GeldmacherMichael Hoelscher
Feb 16, 2010·The Journal of Infectious Diseases·Andrea KovacsLena Al-Harthi
Feb 11, 2010·The Journal of Infectious Diseases·Aimee El HedDerya Unutmaz
Jun 12, 2008·AIDS Research and Human Retroviruses·Martin CadoganAngus G Dalgleish
Feb 3, 2009·AIDS Research and Human Retroviruses·Isaac SsewanyanaHuyen Cao
Nov 6, 2009·AIDS Research and Human Retroviruses·Robert SealyJulia L Hurwitz
Sep 22, 2010·AIDS Research and Human Retroviruses·Reiko TanakaYuetsu Tanaka
Feb 12, 2011·AIDS Research and Human Retroviruses·Gabriella d'EttorreVincenzo Vullo
Aug 8, 2013·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·A MocroftUNKNOWN Opportunistic Infections Working Group on behalf of the Collaboration of Observational HIV Epidemiological Research Europe (
Mar 30, 2012·The Journal of Infectious Diseases·Hiromi Imamichi, H Clifford Lane
Jun 15, 2010·Current Opinion in HIV and AIDS·Nichole R Klatt, Jason M Brenchley
Jan 26, 2012·Current Opinion in HIV and AIDS·Hamayun J SharifiCarlos M C de Noronha
Mar 26, 2008·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Elizabeth SinclairRichard W Price
Feb 6, 2009·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Joseph A PolitchDeborah J Anderson
Feb 9, 2012·Cold Spring Harbor Perspectives in Medicine·Nichole R KlattVanessa Hirsch
Apr 17, 2010·Colorectal Disease : the Official Journal of the Association of Coloproctology of Great Britain and Ireland·M YaghoobiI Sobhani
Oct 17, 2006·Clinical Microbiology Reviews·Sue VandeWoude, Cristian Apetrei

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