The HTLV-1 gp21 fusion peptide inhibits antigen specific T-cell activation in-vitro and in mice

Etai Rotem, Omri Faingold, Meital Charni, Yoel A. Klug, Daniel Harari, Liraz Shmuel-Galia, Alon Nudelman, Varda Rotter, Yechiel Shai*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The ability of the Lentivirus HIV-1 to inhibit T-cell activation by its gp41 fusion protein is well documented, yet limited data exists regarding other viral fusion proteins. HIV-1 utilizes membrane binding region of gp41 to inhibit T-cell receptor (TCR) complex activation. Here we examined whether this T-cell suppression strategy is unique to the HIV-1 gp41. We focused on T-cell modulation by the gp21 fusion peptide (FP) of the Human T-lymphotropic Virus 1 (HTLV-1), a Deltaretrovirus that like HIV infects CD4+T-cells. Using mouse and human in-vitro T-cell models together with in-vivo T-cell hyper activation mouse model, we reveal that HTLV-1’s FP inhibits T-cell activation and unlike the HIV FP, bypasses the TCR complex. HTLV FP inhibition induces a decrease in Th1 and an elevation in Th2 responses observed in mRNA, cytokine and transcription factor profiles. Administration of the HTLV FP in a T-cell hyper activation mouse model of multiple sclerosis alleviated symptoms and delayed disease onset. We further pinpointed the modulatory region within HTLV-1’s FP to the same region previously identified as the HIV-1 FP active region, suggesting that through convergent evolution both viruses have obtained the ability to modulate T-cells using the same region of their fusion protein. Overall, our findings suggest that fusion protein based T-cell modulation may be a common viral trait.

Original languageAmerican English
Article numbere1007044
JournalPLoS Pathogens
Volume14
Issue number5
DOIs
StatePublished - May 2018
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2018 Rotem et al. http://creativecommons.org/licenses/by/4.0/

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