| First Author | Lee S | Year | 2019 |
| Journal | Cell Host Microbe | Volume | 25 |
| Issue | 6 | Pages | 845-857.e5 |
| PubMed ID | 31130511 | Mgi Jnum | J:280247 |
| Mgi Id | MGI:6359106 | Doi | 10.1016/j.chom.2019.04.005 |
| Citation | Lee S, et al. (2019) A Secreted Viral Nonstructural Protein Determines Intestinal Norovirus Pathogenesis. Cell Host Microbe 25(6):845-857.e5 |
| abstractText | 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-lambda (IFN-lambda)-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-lambda resistance. MNoV infection globally suppresses intestinal IFN-lambda 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-lambda 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. |
