Differential regulatory activities of viral protein X for anti-viral efficacy of nucleos(t)ide reverse transcriptase inhibitors in monocyte-derived macrophages and activated CD4(+) T cells

Virology
Joseph A HollenbaughBaek Kim

Abstract

Vpx encoded by HIV-2 and SIVsm enhances retroviral reverse transcription in macrophages in vitro by mediating the degradation of the host SAMHD1 protein that hydrolyzes dNTPs and by elevating cellular dNTP levels. Here we employed RT-SHIV constructs (SIV encoding HIV-1 RT) to investigate the contribution of Vpx to the potency of NRTIs, which compete against dNTPs, in monocyte-derived macrophages (MDMs) and activated CD4(+) T cells. Relative to HIV-1, both SIV and RT-SHIV exhibited reduced sensitivities to AZT, 3TC and TDF in MDMs but not in activated CD4(+) T cells. However, when SIV and RT-SHIV constructs not coding for Vpx were utilized, we observed greater sensitivities to all NRTIs tested using activated CD4(+) T cells relative to the Vpx-coding counterparts. This latter phenomenon was observed for AZT only when using MDMs. Our data suggest that Vpx in RT-SHIVs may underestimate the antiviral efficacy of NRTIs in a cell type dependent manner.

References

Oct 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·W Y GaoF Lori
Oct 19, 2002·Proceedings of the National Academy of Sciences of the United States of America·J RenD K Stammers
Feb 18, 2006·PLoS Pathogens·Paul L BoyerStephen H Hughes
Dec 5, 2006·PLoS Pathogens·Joshua L AndersenVicente Planelles
Apr 2, 2010·Cellular and Molecular Life Sciences : CMLS·Alon Herschhorn, Amnon Hizi
Jun 17, 2010·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·B JulgB D Walker
Apr 22, 2011·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Antoine BenardUNKNOWN ACHIEV2E Collaboration Study Group
Jul 12, 2011·Retrovirology·Corine St Gelais, Li Wu
Aug 22, 2012·Frontiers in Microbiology·Mikako FujitaMasami Otsuka
Sep 14, 2012·Nature Medicine·Hanna-Mari BaldaufOliver T Keppler
Oct 25, 2012·Retrovirology·Benjamin DescoursMonsef Benkirane
Dec 25, 2012·Antimicrobial Agents and Chemotherapy·Christina GavegnanoRaymond F Schinazi
Feb 28, 2013·Retrovirology·Caroline GoujonMichael H Malim
Jul 5, 2013·PLoS Pathogens·Joseph A HollenbaughBaek Kim
Nov 5, 2013·AIDS Research and Human Retroviruses·Sarah B LloydWendy R Winnall
Mar 19, 2014·AIDS Research and Human Retroviruses·Maja StanojevicDjordje Jevtovic
Apr 30, 2014·Antimicrobial Agents and Chemotherapy·Thomas W NorthRaymond F Schinazi
May 29, 2014·Antimicrobial Agents and Chemotherapy·Andrew D HuberStefan G Sarafianos
Jun 11, 2014·Antimicrobial Agents and Chemotherapy·Ester BallanaJosé A Esté
Jul 21, 2014·Nature Medicine·Jeongmin RyooKwangseog Ahn

❮ Previous
Next ❯

Citations

Oct 30, 2016·Molecular Therapy. Methods & Clinical Development·Samantha A McAlleryStuart G Turville
Jan 4, 2017·PloS One·Joseph A HollenbaughBaek Kim

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Antimicrobial Resistance (ASM)

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antimicrobial Resistance

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.