生物
分泌物
病毒学
诺如病毒
向性
干扰素
抗体
鼠诺如病毒
微生物学
分泌蛋白
效应器
免疫学
病毒
生物化学
作者
Sang‐Hyun Lee,Hejun Liu,Craig B. Wilen,Zoi Sychev,Chandni Desai,Barry L. Hykes,Robert C. Orchard,Broc T. McCune,Ki Wook Kim,Timothy J. Nice,Scott A. Handley,Megan T. Baldridge,Gaya K. Amarasinghe,Herbert W. Virgin
标识
DOI:10.1016/j.chom.2019.04.005
摘要
Murine norovirus (MNoV) infects a low percentage of enteric tuft cells and can persist in these cells for months following acute infection. Both tuft-cell tropism and resistance to interferon-λ (IFN-λ)-mediated clearance during persistent infection requires the viral nonstructural protein 1/2 (NS1/2). We show that processing of NS1/2 yields NS1, an unconventionally secreted viral protein that is central for IFN-λ resistance. MNoV infection globally suppresses intestinal IFN-λ responses, which is attributable to secreted NS1. MNoV NS1 secretion is triggered by caspase-3 cleavage of NS1/2, and a secreted form of human NoV NS1 is also observed. NS1 secretion is essential for intestinal infection and resistance to IFN-λ in vivo. NS1 vaccination alone protects against MNoV challenge, despite the lack of induction of neutralizing anti-capsid antibodies previously shown to confer protection. Thus, despite infecting a low number of tuft cells, NS1 secretion allows MNoV to globally suppress IFN responses and promote persistence.
科研通智能强力驱动
Strongly Powered by AbleSci AI