Determinants in HIV-1 Nef for enhancement of virus replication and depletion of CD4+ T lymphocytes in human lymphoid tissue ex vivo.

Retrovirology
Stefanie HomannOliver T Fackler

Abstract

HIV-1 Nef critically contributes to AIDS in part by augmenting virus titers in infected individuals. Analyzing which of Nef's activities contribute to HIV pathogenesis has been hampered by the lack of a cell culture model in which Nef exerts pronounced effects on HIV replication. The human lymphoid aggregate culture (HLAC) from tonsil maintains the cell populations and cytokine milieu found in vivo, supports a productive infection without exogenous stimulation, and Nef contributes to efficient HIV-1 replication as well as CD4+ T cell depletion in this experimental ex vivo-model. To identify determinants in Nef that mediate these activities, we infected HLAC with a panel of isogenic HIV-1NL4-3 strains that encode for well-characterized mutants of HIV-1SF2 Nef. Determination of HIV-1 replication revealed that enhancement of the virus spread by Nef is governed by a complex set of protein interaction surfaces. In contrast, increased CD4+ T lymphocyte depletion depended on only two protein interaction surfaces in Nef that mediate either downregulation of cell surface CD4 or interaction with the NAKC signalosome. Consistently, in HLAC from 9 out of 14 donors, Nef enhanced CD4+ T cell depletion in the absence of a significant effect o...Continue Reading

References

Dec 1, 1995·Nature Medicine·S GlushakovaJ Zimmerberg
Jan 26, 1995·The New England Journal of Medicine·F KirchhoffR C Desrosiers
Aug 1, 1994·Trends in Microbiology·M D MillerW C Greene
Nov 1, 1996·Current Biology : CB·E T SawaiP A Luciw
Jan 20, 1999·Proceedings of the National Academy of Sciences of the United States of America·M L PennL Margolis
Sep 14, 2000·Current Biology : CB·O T Fackler, B M Peterlin
Jul 21, 2001·EMBO Reports·M GeyerB M Peterlin
Apr 3, 2002·Nature Medicine·Zvi GrossmanWilliam E Paul
Jul 2, 2003·Nature Medicine·Mario Stevenson
Feb 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Annette AudigéRoberto F Speck
Feb 24, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Erika SchlaepferRoberto F Speck

❮ Previous
Next ❯

Citations

Feb 15, 2011·Biological Trace Element Research·Michalann Harthill
Jun 5, 2013·Cell Research·Xiaoyu PanOliver T Fackler
Feb 17, 2010·AIDS Research and Human Retroviruses·Syed A AliVincent C Bond
Dec 12, 2012·Cell Communication and Signaling : CCS·Libin Abraham, Oliver T Fackler
Nov 4, 2010·European Journal of Cell Biology·Claudia HallerOliver T Fackler
Jul 17, 2014·Nature Reviews. Microbiology·Oliver T FacklerThorsten R Mempel
Sep 28, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Miguel Lamas-MuruaOliver T Fackler
Nov 5, 2020·The EMBO Journal·Sheetal KawOliver T Fackler

❮ Previous
Next ❯

Methods Mentioned

BETA
ELISA
flow cytometry
myristoylation
transfection
enzyme-linked immunosorbent assay

Software Mentioned

GraphPad Prism
BD CellQuest Pro

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis