Zika Virus Induces Degradation of the Numb Protein Required through Embryonic Neurogenesis

Author:

He Jia1,Yang Liping1,Chang Peixi1,Yang Shixing1ORCID,Wang Yu1,Lin Shaoli1,Tang Qiyi2ORCID,Zhang Yanjin1ORCID

Affiliation:

1. Molecular Virology Laboratory, Department of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA

2. Department of Microbiology, Howard University College of Medicine, Washington, DC 20059, USA

Abstract

Zika virus (ZIKV) is a mosquito-borne flavivirus and causes an infection associated with congenital Zika syndrome and Guillain–Barre syndrome. The mechanism of ZIKV-mediated neuropathogenesis is not well understood. In this study, we discovered that ZIKV induces degradation of the Numb protein, which plays a crucial role in neurogenesis by allowing asymmetric cell division during embryonic development. Our data show that ZIKV reduced the Numb protein level in a time- and dose-dependent manner. However, ZIKV infection appears to have minimal effect on the Numb transcript. Treatment of ZIKV-infected cells with a proteasome inhibitor restores the Numb protein level, which suggests the involvement of the ubiquitin–proteasome pathway. In addition, ZIKV infection shortens the half-life of the Numb protein. Among the ZIKV proteins, the capsid protein significantly reduces the Numb protein level. Immunoprecipitation of the Numb protein co-precipitates the capsid protein, indicating the interaction between these two proteins. These results provide insights into the ZIKV–cell interaction that might contribute to its impact on neurogenesis.

Funder

Faculty-Student Research Award from the Graduate School, University of Maryland

Publisher

MDPI AG

Subject

Virology,Infectious Diseases

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