Fitness cost of escape mutations in p24 Gag in association with control of human immunodeficiency virus type 1

Journal of Virology
Javier Martinez-PicadoPhilip Goulder

Abstract

Mutational escape by human immunodeficiency virus (HIV) from cytotoxic T-lymphocyte (CTL) recognition is a major challenge for vaccine design. However, recent studies suggest that CTL escape may carry a sufficient cost to viral replicative capacity to facilitate subsequent immune control of a now attenuated virus. In order to examine how limitations can be imposed on viral escape, the epitope TSTLQEQIGW (TW10 [Gag residues 240 to 249]), presented by two HLA alleles associated with effective control of HIV, HLA-B*57 and -B*5801, was investigated. The in vitro experiments described here demonstrate that the dominant TW10 escape mutation, T242N, reduces viral replicative capacity. Structural analysis reveals that T242 plays a critical role in defining the start point and in stabilizing helix 6 within p24 Gag, ensuring that escape occurs at a significant cost. A very similar role is played by Thr-180, which is also an escape residue, but within a second p24 Gag epitope associated with immune control. Analysis of HIV type 1 gag in 206 B*57/5801-positive subjects reveals three principle alternative TW10-associated variants, and each is strongly linked to concomitant additional variants within p24 Gag, suggesting that functional const...Continue Reading

References

Apr 1, 1994·AIDS Research and Human Retroviruses·J S GibbsR C Desrosiers
Sep 1, 1996·Nature Structural Biology·C MomanyM G Rossmann
Mar 26, 1998·Protein Science : a Publication of the Protein Society·R Aurora, G D Rose
Dec 11, 1999·Nucleic Acids Research·H M BermanP E Bourne
May 29, 2002·Nature Structural Biology·Chun TangMichael F Summers
Apr 15, 2003·Journal of Virology·Uta K von SchwedlerWesley I Sundquist
Feb 11, 2004·Nature Medicine·A J LeslieP J R Goulder
Feb 18, 2004·Nature Medicine·Thomas C FriedrichDavid I Watkins
Apr 7, 2004·The Journal of Experimental Medicine·Rika DraenertPhilip J R Goulder
Jun 24, 2004·The Journal of Experimental Medicine·Tetsuro MatanoYoshiyuki Nagai
Aug 3, 2004·Nature Reviews. Immunology·Philip J R Goulder, David I Watkins
Dec 4, 2004·Journal of Acquired Immune Deficiency Syndromes : JAIDS·David PaoPatricia Cane
Dec 14, 2004·Nature·Photini KiepielaPhilip J R Goulder
Feb 18, 2005·Nature Immunology·Mina John, Simon Mallal
Mar 23, 2005·The Journal of Experimental Medicine·Alasdair LesliePhilip Goulder
Jun 10, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Margaret E FeeneyPhilip J R Goulder

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Citations

Mar 7, 2007·Current HIV/AIDS Reports·Kenneth R HenryEric J Arts
Feb 28, 2007·Current Infectious Disease Reports·Nicole Frahm, Christian Brander
Oct 1, 2011·Molecular Biotechnology·Alexander ZawairaDenis Chopera
Feb 27, 2009·Nature·Yuka KawashimaPhilip Goulder
Nov 11, 2008·Nature Medicine·Angel Varela-RohenaJames L Riley
Jun 12, 2010·Nature Protocols·Asier Sáez-CiriónGianfranco Pancino
Jul 12, 2008·Nature Reviews. Immunology·Philip J R Goulder, David I Watkins
Dec 17, 2009·Nature Reviews. Immunology·Andrew J McMichaelBarton F Haynes
Dec 18, 2010·Nature Reviews. Immunology·Richard A KoupDaniel C Douek
Aug 25, 2012·Nature Reviews. Immunology·Andrew J PrendergastPhilip J R Goulder
Jan 5, 2007·Nature Reviews. Microbiology·Kevin K AriënEric J Arts
Aug 11, 2010·Proceedings of the National Academy of Sciences of the United States of America·Natasja G de GrootRonald E Bontrop
May 7, 2008·The Journal of Experimental Medicine·Todd M Allen, Marcus Altfeld
Mar 25, 2009·The Journal of Experimental Medicine·Hayley CrawfordEric Hunter
Jun 3, 2009·The Journal of Experimental Medicine·Nilu GoonetillekeAndrew J McMichael
Jan 8, 2008·The Journal of Infectious Diseases·Victor Sanchez-MerinoKatherine Luzuriaga
Feb 16, 2008·The Journal of Infectious Diseases·Florencia PereyraBruce D Walker
Nov 17, 2009·The Journal of Infectious Diseases·Yi LiuJames I Mullins
Mar 31, 2009·AIDS Research and Human Retroviruses·Christine M RousseauJames I Mullins
Apr 12, 2011·AIDS Research and Human Retroviruses·Bongeka NqokoWillem A Hanekom
Jun 26, 2013·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Hiroyuki GatanagaShinichi Oka
Mar 16, 2011·The Journal of Infectious Diseases·Jonathan Z LiUNKNOWN AIDS Clinical Trials Group A5197 Study Team
Jul 24, 2013·The Journal of Infectious Diseases·Holly JanesNicole Frahm
Apr 18, 2009·Current Opinion in HIV and AIDS·Peter W Hunt, Mary Carrington
Jun 18, 2009·Current Opinion in HIV and AIDS·Zenda Woodman, Carolyn Williamson
Jun 6, 2008·AIDS·Yoav PeretzNicole F Bernard
Mar 24, 2012·AIDS·Adrian B McDermott, Richard A Koup
Nov 17, 2009·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Becky SchweighardtFrederick M Hecht

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