HIV-1 Structural Proteins Serve as PAMPs for TLR2 Heterodimers Significantly Increasing Infection and Innate Immune Activation

Frontiers in Immunology
Bethany M HenrickINFANT Study Team

Abstract

Immune activation is critical to HIV infection and pathogenesis; however, our understanding of HIV innate immune activation remains incomplete. Recently we demonstrated that soluble TLR2 (sTLR2) physically inhibited HIV-induced NFκB activation and inflammation, as well as HIV-1 infection. In light of these findings, we hypothesized that HIV-1 structural proteins may serve as pathogen-associated molecular patterns (PAMPs) for cellular TLR2 heterodimers. These studies made use of primary human T cells and TZMbl cells stably transformed to express TLR2 (TZMbl-2). Our results demonstrated that cells expressing TLR2 showed significantly increased proviral DNA compared to cells lacking TLR2, and mechanistically this may be due to a TLR2-mediated increased CCR5 expression. Importantly, we show that HIV-1 structural proteins, p17, p24, and gp41, act as viral PAMPs signaling through TLR2 and its heterodimers leading to significantly increased immune activation via the NFκB signaling pathway. Using co-immunoprecipitation and a dot blot method, we demonstrated direct protein interactions between these viral PAMPs and TLR2, while only p17 and gp41 bound to TLR1. Specifically, TLR2/1 heterodimer recognized p17 and gp41, while p24 lead to im...Continue Reading

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Citations

Mar 1, 2016·Frontiers in Immunology·Aline IgnacioRafael Ribeiro Almeida
Aug 18, 2016·Frontiers in Immunology·Bethany M HenrickKenneth Lee Rosenthal
Oct 4, 2016·Frontiers in Immunology·Maria Fernanda PascuttiMartijn A Nolte
Aug 26, 2016·Clinical Microbiology Reviews·Véronique Avettand-FènoëlChristine Rouzioux
Aug 20, 2018·International Journal of Cancer. Journal International Du Cancer·Gordana HalecAnna-Barbara Moscicki
Aug 6, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Yi ZheHang-Yu Li
Aug 21, 2019·Natural Product Research·Bruna BensoRamiro Mendonça Murata
Apr 2, 2019·Frontiers in Immunology·Bethany M HenrickKenneth L Rosenthal
Jun 25, 2020·Nature Communications·José A Aguilar-BriseñoIzabela A Rodenhuis-Zybert
Aug 2, 2020·Scientific Reports·Muhammad Atif ZahoorKenneth L Rosenthal
Oct 14, 2020·Scandinavian Journal of Immunology·Si-Biao SuHai-Xing Jiang
Nov 19, 2020·Microorganisms·Edward P Browne
Aug 11, 2021·Journal of Medical Virology·Rui ZhouYu Wang
Mar 4, 2019·The Canadian Journal of Cardiology·Arjun Sinha, Matthew J Feinstein

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Methods Mentioned

BETA
co-IP
ELISAs
electrophoresis
transfection
ELISA
dot blot
Immunoprecipitation
nuclear translocation

Software Mentioned

GraphPad Prism
Primer
GraphPad

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