Intrinsic obstacles to human immunodeficiency virus type 1 coreceptor switching

Journal of Virology
Cristina PastoreDonald E Mosier

Abstract

The natural evolution of human immunodeficiency virus type 1 infection often includes a switch in coreceptor preference late in infection from CCR5 to CXCR4, a change associated with expanded target cell range and worsened clinical prognosis. Why coreceptor switching takes so long is puzzling, since it requires as few as one to two mutations. Here we report three obstacles that impede the CCR5-to-CXCR4 switch. Coreceptor switch variants were selected by target cell replacement in vitro. Most switch variants showed diminished replication compared to their parental R5 isolate. Transitional intermediates were more sensitive to both CCR5 and CXCR4 inhibitors than either the parental R5 virus or the final R5X4 (or rare X4) variant. The small number of mutations in viruses selected for CXCR4 use were distinctly nonrandom, with a dominance of charged amino acid substitutions encoded by G-to-A transitions, changes in N-linked glycosylation sites, and isolate-specific mutation patterns. Diminished replication fitness, less-efficient coreceptor use, and unique mutational pathways may explain the long delay from primary infection until the emergence of CXCR4-using viruses.

References

Oct 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·T ShiodaC Cheng-Mayer
Apr 1, 1994·Antimicrobial Agents and Chemotherapy·E De ClercqR Datema
Feb 17, 1997·The Journal of Experimental Medicine·R I ConnorN R Landau
Jan 14, 1998·Nature Medicine·G A DonzellaJ P Moore
Jan 10, 2002·Proceedings of the National Academy of Sciences of the United States of America·Alexandra TrkolaJohn P Moore
Feb 13, 2002·AIDS Research and Human Retroviruses·Ben BerkhoutVladimir V Lukashov
Nov 22, 2002·Proceedings of the National Academy of Sciences of the United States of America·Jacqueline D ReevesRobert W Doms
Dec 28, 2002·Journal of Virology·Béatrice LabrosseFabrizio Mammano
Jan 25, 2003·Antimicrobial Agents and Chemotherapy·Cristina PastoreDonald E Mosier
Jun 18, 2003·Cell·Reuben S HarrisMichael H Malim

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Citations

Apr 7, 2010·Archivum Immunologiae Et Therapiae Experimentalis·Milan Raska, Jan Novak
Nov 7, 2006·Bulletin of Mathematical Biology·T Mugwagwa, G Witten
Jun 7, 2005·Trends in Microbiology·Roland R Regoes, Sebastian Bonhoeffer
Jun 6, 2008·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Rodger D MacArthur, Richard M Novak
Feb 24, 2005·AIDS Research and Human Retroviruses·Oliver HartleyJohn P Moore
Apr 7, 2007·AIDS Research and Human Retroviruses·Timothy CardozoSusan Zolla-Pazner
Feb 15, 2008·AIDS Research and Human Retroviruses·Maria LahuertaDenise Naniche
Apr 3, 2009·Current Opinion in HIV and AIDS·John P Moore, Daniel R Kuritzkes
Sep 26, 2008·Journal of Virology·Mia CoetzerDonald E Mosier
Oct 17, 2007·Annual Review of Pharmacology and Toxicology·Shawn E Kuhmann, Oliver Hartley
Feb 10, 2011·Journal of Translational Medicine·Hanneke SchuitemakerPaolo Lusso
Feb 10, 2011·Journal of Translational Medicine·Jean-Charles GrivelLeonid B Margolis
Feb 10, 2011·Journal of Translational Medicine·Silvana Tasca SinaCecilia Cheng-Mayer
Feb 10, 2011·Journal of Translational Medicine·Bruce L GilliamRobert R Redfield
Nov 19, 2013·PloS One·Virginie MortierChris Verhofstede
May 25, 2005·Proceedings of the National Academy of Sciences of the United States of America·Yoshiaki NishimuraMalcolm A Martin
Oct 25, 2014·Viruses·Pinar Iyidogan, Karen S Anderson
Apr 26, 2006·Expert Opinion on Investigational Drugs·Priscilla BiswasGiuseppe Tambussi
Jan 8, 2011·Enfermedades infecciosas y microbiología clínica·Rafael Delgado
Jul 21, 2009·Antiviral Research·Luis Menéndez-Arias
Mar 1, 2008·Médecine et maladies infectieuses·X de la TribonnièreJ Reynes
May 13, 2008·Drug Discovery Today·Catherine S Adamson, Eric O Freed
Feb 6, 2014·Journal of Evolutionary Biology·J da Silva, S K Wyatt
Nov 10, 2009·Evolution; International Journal of Organic Evolution·Jack da Silva

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