Viruses, Vol. 12, Pages 409: Influenza PB1-F2 Inhibits Avian MAVS Signaling

Viruses, Vol. 12, Pages 409: Influenza PB1-F2 Inhibits Avian MAVS Signaling Viruses doi: 10.3390/v12040409 Authors: Yanna Xiao Danyel Evseev Chase A. Stevens Adam Moghrabi Domingo Miranzo-Navarro Ximena Fleming-Canepa David G. Tetrault Katharine E. Magor RIG-I plays an essential role in the duck innate immune response to influenza infection. RIG-I engages the critical adaptor protein mitochondrial antiviral signaling (MAVS) to activate the downstream signaling pathway. The influenza A virus non-structural protein PB1-F2 interacts with MAVS in human cells to inhibit interferon production. As duck and human MAVS share only 28% amino acid similarity, it is not known whether the influenza virus can similarly inhibit MAVS signaling in avian cells. Using confocal microscopy we show that MAVS and the constitutively active N-terminal end of duck RIG-I (2CARD) co-localize in DF-1 cells, and duck MAVS is pulled down with GST-2CARD. We establish that either GST-2CARD, or duck MAVS can initiate innate signaling in chicken cells and their co-transfection augments interferon-beta promoter activity. Demonstrating the limits of cross-species interactions, duck RIG-I 2CARD initiates MAVS signaling in chicken cells, but works poorly in human cells. The D122A mutation of human 2CARD abrogates signaling by affecting MAVS engagement, and the reciprocal A120D mutation in duck 2CARD improves signaling in human cells. We show mitochondrial localization of PB1-F2 from influenza ...
Source: Viruses - Category: Virology Authors: Tags: Article Source Type: research