Necroptosis-based CRISPR knockout screen reveals Neuropilin-1 as a critical host factor for early stages of murine cytomegalovirus infection

Rebecca K. Lane, Hongyan Guo, Amanda D. Fisher, Jonathan Diep, Zhao Lai, Yidong Chen, Jason W. Upton, Jan Carette, Edward S. Mocarski, William J. Kaiser

Research output: Contribution to journalArticlepeer-review

Abstract

Herpesviruses are ubiquitous human pathogens that cause a wide range of health complications. Currently, there is an incomplete understanding of cellular factors that contribute to herpesvirus infection. Here, we report an antiviral necroptosis-based genetic screen to identify novel host cell factors required for infection with the β-herpesvirus murine cytomegalovirus (MCMV). Our genomewide CRISPR-based screen harnessed the capacity of herpesvirus mutants that trigger antiviral necroptotic cell death upon early viral gene expression. Vascular endothelial growth factor (VEGF) and semaphorin-binding receptor Neuropilin-1 (Nrp-1) emerge as crucial determinants of MCMV infection. We find that elimination of Nrp-1 impairs early viral gene expression and reduces infection rates in endothelial cells, fibroblasts, and macrophages. Furthermore, preincubation of virus with soluble Nrp-1 dramatically inhibits infection by reducing virus attachment. Thus, Nrp-1 is a key determinant of the initial phase of MCMV infection.

Original languageEnglish (US)
Pages (from-to)20109-20116
Number of pages8
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number33
DOIs
StatePublished - Aug 2020

ASJC Scopus subject areas

  • General

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