Mutation of a Conserved Nuclear Export Sequence in Chikungunya Virus Capsid Protein Disrupts Host Cell Nuclear Import

Viruses. 2017 Oct 20;9(10):306. doi: 10.3390/v9100306.

Abstract

Transmitted by mosquitoes; chikungunya virus (CHIKV) is responsible for frequent outbreaks of arthritic disease in humans. CHIKV is an arthritogenic alphavirus of the Togaviridae family. Capsid protein, a structural protein encoded by the CHIKV RNA genome, is able to translocate to the host cell nucleus. In encephalitic alphaviruses nuclear translocation induces host cell shut off; however, the role of capsid protein nuclear localisation in arthritogenic alphaviruses remains unclear. Using replicon systems, we investigated a nuclear export sequence (NES) in the N-terminal region of capsid protein; analogous to that found in encephalitic alphavirus capsid but uncharacterised in CHIKV. The chromosomal maintenance 1 (CRM1) export adaptor protein mediated CHIKV capsid protein export from the nucleus and a region within the N-terminal part of CHIKV capsid protein was required for active nuclear targeting. In contrast to encephalitic alphaviruses, CHIKV capsid protein did not inhibit host nuclear import; however, mutating the NES of capsid protein (∆NES) blocked host protein access to the nucleus. Interactions between capsid protein and the nucleus warrant further investigation.

Keywords: alphavirus; capsid protein; chikungunya virus; nuclear export.

MeSH terms

  • Active Transport, Cell Nucleus*
  • Capsid Proteins / chemistry
  • Capsid Proteins / genetics*
  • Capsid Proteins / metabolism*
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Chikungunya Fever / virology
  • Chikungunya virus / genetics*
  • Chikungunya virus / physiology
  • Exportin 1 Protein
  • Host-Pathogen Interactions*
  • Humans
  • Karyopherins / genetics
  • Karyopherins / metabolism
  • Mutation*
  • Nuclear Export Signals
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Replicon
  • Virion / genetics
  • Virus Replication

Substances

  • Capsid Proteins
  • Karyopherins
  • Nuclear Export Signals
  • Receptors, Cytoplasmic and Nuclear