The Cellular NMD Pathway Restricts Zika Virus Infection and Is Targeted by the Viral Capsid Protein
Abstract
Zika virus (ZIKV) is a significant global health threat, as infection has been linked to serious neurological complications, including microcephaly. Using a human stem cell-derived neural progenitor model system, we find that a critical cellular quality control process called the nonsense-mediated mRNA decay (NMD) pathway is disrupted during ZIKV infection. Importantly, disruption of the NMD pathway is a known cause of microcephaly and other neurological disorders. We further identify an interaction between the capsid protein of ZIKV and up-frameshift protein 1 (UPF1), the master regulator of NMD, and show that ZIKV capsid targets UPF1 for degradation. Together, these results offer a new mechanism for how ZIKV infection can cause neuropathology in the developing brain.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Dec 21, 2018
- Source ID
- 10.1128/mbio.02126-18
Entities
People
- David Jimenez-Morales
- Julia A. Kaye
- Kristoffer E Leon
- Krystal A. Fontaine
- Mariah Dunlap
- Melanie Ott
- Mir M. Khalid
- Nevan J. Krogan
- Priya S. Shah
- Sakshi Tomar
- Steve Finkbeiner
Organizations
- Gladstone Institutes
- James B. Pendleton Charitable Trust
- National Institute of Allergy and Infectious Diseases
- National Institute of Neurological Disorders and Stroke
- University of California
- University of California, San Francisco