期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 117, 期 33, 页码 20109-20116出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1921315117
关键词
cytomegolovirus; necroptosis; neuropilin; CRISPR
资金
- University of Texas Health San Antonio, Grant NIH-National Cancer Institute (NCI) [P30 CA054174-20, UL1 TR001120]
- UTHSCSA
- NIH-NCI [P30 CA054174]
- Cancer Prevention and Research Institute of Texas Core Facility Award [RP160732]
- NIH [R01 AI141970, DP5 OD012198]
- Craniofacial Oral-biology Student Training in Academic Research fellowship award [T32DE014318-16]
- National Institute of Dental and Craniofacial Research F31 predoctoral fellowship [F31DE029395]
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 beta-herpesvirus murine cytomegalovirus (MCMV). Our genome-wide 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. Further-more, preincubation of virus with soluble Nrp-1 dramatically in-hibits infection by reducing virus attachment. Thus, Nrp-1 is a key determinant of the initial phase of MCMV infection.
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