Entry by multiple picornaviruses is dependent on a pathway that includes TNK2, WASL, and NCK1.

Abstract

Comprehensive knowledge of the host factors required for picornavirus infection would facilitate antiviral development. Here we demonstrate roles for three human genes, TNK2, WASL, and NCK1, in infection by multiple picornaviruses. CRISPR deletion of TNK2, WASL, or NCK1 reduced encephalomyocarditis virus (EMCV), coxsackievirus B3 (CVB3), poliovirus and enterovirus D68 infection, and chemical inhibitors of TNK2 and WASL decreased EMCV infection. Reduced EMCV lethality was observed in mice lacking TNK2. TNK2, WASL, and NCK1 were important in early stages of the viral lifecycle, and genetic epistasis analysis demonstrated that the three genes function in a common pathway. Mechanistically, reduced internalization of EMCV was observed in TNK2 deficient cells demonstrating that TNK2 functions in EMCV entry. Domain analysis of WASL demonstrated that its actin nucleation activity was necessary to facilitate viral infection. Together, these data support a model wherein TNK2, WASL, and NCK1 comprise a pathway important for multiple picornaviruses.

• Authors: Hongbing Jiang, Christian Leung, Stephen Tahan, David Wang
• Journal: eLife (Elife) Vol. 8 (11 26 2019) ISSN: 2050-084X [Electronic] England
• PMID: 31769754 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2019, Jiang et al.

Chemical References

• Adaptor Proteins, Signal Transducing
• Nck protein
• Oncogene Proteins
• WASL protein, human
• Wiskott-Aldrich Syndrome Protein, Neuronal
• Tnk2 protein, mouse
• Protein-Tyrosine Kinases
• TNK2 protein, human

Topics

• Adaptor Proteins, Signal Transducing (deficiency, metabolism)
• Animals
• Cardiovirus Infections (pathology)
• Cell Line
• Disease Models, Animal
• Gene Deletion
• Host-Pathogen Interactions
• Humans
• Mice, Knockout
• Oncogene Proteins (deficiency, metabolism)
• Picornaviridae (growth & development)
• Protein-Tyrosine Kinases (antagonists & inhibitors, deficiency, metabolism)
• Survival Analysis
• Virus Internalization
• Wiskott-Aldrich Syndrome Protein, Neuronal (antagonists & inhibitors, deficiency, metabolism)