Zika virus NS5 localizes at centrosomes during cell division

Aditi S Kesari; Veronica J Heintz; Shishir Poudyal; Andrew S Miller; Richard J Kuhn; Douglas J LaCount

doi:10.1016/j.virol.2019.11.018

Zika virus NS5 localizes at centrosomes during cell division

Virology. 2020 Feb:541:52-62. doi: 10.1016/j.virol.2019.11.018. Epub 2019 Dec 6.

Authors

Aditi S Kesari¹, Veronica J Heintz¹, Shishir Poudyal², Andrew S Miller², Richard J Kuhn², Douglas J LaCount³

Affiliations

¹ Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, 47907, USA; Department of Molecular Pharmacology, Purdue University, West Lafayette, IN, 47907, USA; Purdue Institute of Inflammation, Immunology and Infectious Disease, Purdue University, West Lafayette, IN, 47907, USA.
² Department of Biological Sciences, Purdue University, West Lafayette, IN, 47907, USA; Purdue Institute of Inflammation, Immunology and Infectious Disease, Purdue University, West Lafayette, IN, 47907, USA.
³ Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, 47907, USA; Department of Molecular Pharmacology, Purdue University, West Lafayette, IN, 47907, USA; Purdue Institute of Inflammation, Immunology and Infectious Disease, Purdue University, West Lafayette, IN, 47907, USA. Electronic address: dlacount@purdue.edu.

Abstract

Zika virus (ZIKV) nonstructural protein 5 (NS5) plays a critical role in viral RNA replication and mediates key virus-host cell interactions. As with other flavivirus NS5 proteins, ZIKV NS5 is primarily found in the nucleus. We previously reported that the NS5 protein of dengue virus, another flavivirus, localized to centrosomes during cell division. Here we show that ZIKV NS5 also relocalizes from the nucleus to centrosomes during mitosis. In infected cells with supernumerary centrosomes, NS5 was present at all centrosomes. Transient expression of NS5 in uninfected cells confirmed that centrosomal localization was independent of other viral proteins. Live-cell imaging demonstrated that NS5-GFP accumulated at centrosomes shortly after break down of nuclear membrane and remained there through mitosis. Cells expressing NS5-GFP took longer to complete mitosis than control cells. Finally, an analysis of ZIKV NS5 binding partners revealed several centrosomal proteins, providing potential direct links between NS5 and centrosomes.

Keywords: Centrosome; Flavivirus; Nonstructural protein NS5; RNA-Dependent RNA polymerase; Zika virus.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Centrosome / metabolism*
HEK293 Cells
Humans
Mitosis
Viral Nonstructural Proteins / metabolism*

Substances

NS5 protein, flavivirus
Viral Nonstructural Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding