A Secreted Viral Nonstructural Protein Determines Intestinal Norovirus Pathogenesis
| Autor: | Megan T. Baldridge, Herbert W. Virgin, Sanghyun Lee, Gaya K. Amarasinghe, Hejun Liu, Barry L. Hykes, Craig B. Wilen, Broc T. McCune, Scott A. Handley, Robert C. Orchard, Chandni Desai, Timothy J. Nice, Ki-Wook Kim, Zoi E. Sychev |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Virulence Factors
Viral nonstructural protein Viral protein viruses ved/biology.organism_classification_rank.species Viral Nonstructural Proteins Biology medicine.disease_cause Microbiology Article Pathogenesis Mice 03 medical and health sciences 0302 clinical medicine Virology medicine Animals Humans Secretion Tropism Caliciviridae Infections Immune Evasion 030304 developmental biology 0303 health sciences ved/biology Norovirus virus diseases biochemical phenomena metabolism and nutrition Gastroenteritis Vaccination Disease Models Animal biology.protein Cytokines Parasitology Antibody 030217 neurology & neurosurgery Murine norovirus |
| Zdroj: | Cell Host Microbe |
| ISSN: | 1931-3128 |
| DOI: | 10.1016/j.chom.2019.04.005 |
| Popis: | Summary 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|