Canine parvovirus induces G1/S cell cycle arrest that involves EGFR Tyr1086 phosphorylation

Xiaofeng Dai; Xuanhao Zhang; Yujie Miao; Peiyu Han; Jianying Zhang

doi:10.1080/21505594.2020.1814091

Canine parvovirus induces G1/S cell cycle arrest that involves EGFR Tyr1086 phosphorylation

Virulence. 2020 Dec;11(1):1203-1214. doi: 10.1080/21505594.2020.1814091.

Authors

Xiaofeng Dai^{1

2}, Xuanhao Zhang³, Yujie Miao, Peiyu Han², Jianying Zhang^{4

5}

Affiliations

¹ Wuxi School of Medicine, Jiangnan University , Wuxi, China.
² The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an, China.
³ School of Biotechnology, Jiangnan University , Wuxi, China.
⁴ Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University , Zhengzhou, Henan, China.
⁵ Department of Biological Sciences, University of Texas at El Paso , El Paso, TX, USA.

Abstract

Canine parvovirus (CPV) has been used in cancer control as a drug delivery vehicle or anti-tumor reagent due to its multiple natural advantages. However, potential host cell cycle arrest induced by virus infection may impose a big challenge to CPV associated cancer control as it could prevent host cancer cells from undergoing cell lysis and foster them regain viability once the virotherapy was ceased. To explore CPV-induced cell cycle arrest and the underlying mechanism toward improved virotherapeutic design, we focus on epidermal growth factor receptor (EGFR), a cellular receptor interacting with TfR that mediates CPV-host interactions, and alterations on its tyrosine phosphorylation sites in response to CPV infection. We found that CPV could trigger host G1/S cell cycle arrest via the EGFR (Y1086)/p27 and EGFR (Y1068)/STAT3/cyclin D1 axes, and EGFR inhibitor could not reverse this process. Our results contribute to our understandings on the mechanism of CPV-induced host cellular response and can be used in the onco-therapeutic design utilizing CPV by preventing host cancer cells from entering cell cycle arrest.

Keywords: Canine parvovirus; EGFR; cell cycle arrest; virotherapy.

MeSH terms

Animals
Cats
Cell Line
Dogs
ErbB Receptors / genetics
ErbB Receptors / metabolism*
G1 Phase Cell Cycle Checkpoints*
Host-Pathogen Interactions*
Madin Darby Canine Kidney Cells
Parvoviridae Infections / physiopathology
Parvoviridae Infections / virology
Parvovirus, Canine / pathogenicity*
Phosphorylation
S Phase Cell Cycle Checkpoints*

Substances

ErbB Receptors

Grants and funding

This study was funded by the National Natural Science Foundation of China (Grant No. 81972789), the National Science and Technology Major Project (Grant No. 2018ZX10302205-004-002), Fundamental Research Funds for the Central Universities (Grant No. JUSRP22011), Technology Development Funding of Wuxi (Grant No. WX18IVJN017) and Research Funding from DaBeiNong Group, China. These funding sources have no role in the writing of the manuscript or the decision to submit it for publication.