Transmission of HIV-1 Gag immune escape mutations is associated with reduced viral load in linked recipients.

The Journal of Experimental Medicine
Paul A GoepfertEric Hunter

Abstract

In a study of 114 epidemiologically linked Zambian transmission pairs, we evaluated the impact of human leukocyte antigen class I (HLA-I)-associated amino acid polymorphisms, presumed to reflect cytotoxic T lymphocyte (CTL) escape in Gag and Nef of the virus transmitted from the chronically infected donor, on the plasma viral load (VL) in matched recipients 6 mo after infection. CTL escape mutations in Gag and Nef were seen in the donors, which were subsequently transmitted to recipients, largely unchanged soon after infection. We observed a significant correlation between the number of Gag escape mutations targeted by specific HLA-B allele-restricted CTLs and reduced VLs in the recipients. This negative correlation was most evident in newly infected individuals, whose HLA alleles were unable to effectively target Gag and select for CTL escape mutations in this gene. Nef mutations in the donor had no impact on VL in the recipient. Thus, broad Gag-specific CTL responses capable of driving virus escape in the donor may be of clinical benefit to both the donor and recipient. In addition to their direct implications for HIV-1 vaccine design, these data suggest that CTL-induced viral polymorphisms and their associated in vivo viral ...Continue Reading

References

Aug 1, 1993·Journal of Virology·D C ShugarsR Swanstrom
Feb 11, 2004·Nature Medicine·A J LeslieP J R Goulder
Apr 7, 2004·The Journal of Experimental Medicine·Rika DraenertPhilip J R Goulder
Jun 23, 2004·Nature Structural & Molecular Biology·Jason LanmanPeter E Prevelige
Aug 3, 2004·Nature Reviews. Immunology·Philip J R Goulder, David I Watkins
Sep 15, 2004·The Journal of Experimental Medicine·Jason M BrenchleyDaniel C Douek
Dec 14, 2004·Nature·Photini KiepielaPhilip J R Goulder
Mar 23, 2005·The Journal of Experimental Medicine·Alasdair LesliePhilip Goulder
Oct 6, 2005·The Journal of Infectious Diseases·Danni RamduthBruce Walker
Nov 15, 2005·AIDS·Jonathan ElfordGraham Hart
May 10, 2006·The Journal of Experimental Medicine·Justin R BaileyJoel N Blankson
Sep 20, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Alasdair LesliePhilip J R Goulder
Jul 6, 2007·PloS One·Jonathan CarlsonDavid Heckerman
Aug 19, 2007·Journal of Virology·Thomas KuntzenTodd M Allen
Nov 21, 2007·The Journal of Experimental Medicine·Galit AlterMarcus Altfeld

❮ Previous
Next ❯

Citations

Apr 30, 2013·Bio Systems·Faraimunashe Chirove, Edward M Lungu
Feb 27, 2009·Nature·Yuka KawashimaPhilip Goulder
Jul 12, 2008·Nature Reviews. Immunology·Philip J R Goulder, David I Watkins
Dec 17, 2009·Nature Reviews. Immunology·Andrew J McMichaelBarton F Haynes
Apr 20, 2011·Proceedings of the National Academy of Sciences of the United States of America·Amy W ChungIvan Stratov
May 7, 2008·The Journal of Experimental Medicine·Todd M Allen, Marcus Altfeld
Mar 25, 2009·The Journal of Experimental Medicine·Hayley CrawfordEric Hunter
Jan 13, 2010·The Journal of Experimental Medicine·Anju BansalPaul A Goepfert
Sep 25, 2010·The Journal of Infectious Diseases·Hendrik Streeck, Douglas F Nixon
Sep 25, 2010·The Journal of Infectious Diseases·Christian L BoutwellTodd M Allen
Mar 31, 2009·AIDS Research and Human Retroviruses·Christine M RousseauJames I Mullins
Apr 9, 2010·Viral Immunology·Michel L NdongalaNicole F Bernard
Mar 16, 2011·The Journal of Infectious Diseases·Jonathan Z LiUNKNOWN AIDS Clinical Trials Group A5197 Study Team
Jun 18, 2009·Current Opinion in HIV and AIDS·Zenda Woodman, Carolyn Williamson
Nov 12, 2009·AIDS·Ana I Fontaine CostaCan Keşmir
Mar 24, 2012·AIDS·Adrian B McDermott, Richard A Koup
Dec 3, 2010·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Zabrina L BrummeMark A Brockman
Jul 20, 2012·Journal of Virology·Catherine A BrennanBeth D Jamieson
May 28, 2010·Journal of Virology·Toshiyuki MiuraBruce D Walker
Jul 4, 2008·Journal of Virology·Philippa C MatthewsPhilip J R Goulder
Dec 19, 2008·Journal of Virology·Arne SchneidewindTodd M Allen
Dec 17, 2010·Journal of Virology·LaTonya D WilliamsPaul A Goepfert
Mar 2, 2012·Journal of Virology·Jonathan M CarlsonDavid Heckerman

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
genotyping
electrophoresis

Software Mentioned

Sequencher

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.