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

Susan C Jacobs1, Adam Taylor2, Lara J Herrero3

  • 1The Roslin Institute, The University of Edinburgh, Midlothian EH25 9RG, UK. jacobs_susan@hotmail.com.

Viruses
|October 21, 2017
PubMed

Insights

Chikungunya virus (CHIKV) capsid protein moves to the nucleus, but unlike other alphaviruses, it doesn't shut down host cells. Its nuclear export is CRM1-dependent, and mutations block nuclear entry.

Area of Science:

  • Virology
  • Molecular Biology
  • Cell Biology

Background:

  • Chikungunya virus (CHIKV) causes widespread arthritic disease outbreaks.
  • CHIKV is an arthritogenic alphavirus within the Togaviridae family.
  • The CHIKV capsid protein can translocate into the host cell nucleus, but its role in arthritogenic alphaviruses is not fully understood.

Purpose of the Study:

  • To investigate the nuclear import and export mechanisms of the CHIKV capsid protein.
  • To characterize the function of a putative nuclear export sequence (NES) in the CHIKV capsid protein.
  • To compare the nuclear interactions of CHIKV capsid protein with those of encephalitic alphaviruses.

Main Methods:

  • Utilized CHIKV replicon systems to study capsid protein nuclear localization.
  • Investigated the role of a nuclear export sequence (NES) in the N-terminal region of the capsid protein.
  • Examined the involvement of the chromosomal maintenance 1 (CRM1) export adaptor protein in nuclear export.
  • Assessed the impact of NES mutations on host protein nuclear import.

Main Results:

  • CHIKV capsid protein possesses an NES in its N-terminal region, mediating nuclear export via CRM1.
  • A specific N-terminal region is crucial for the active nuclear targeting of CHIKV capsid protein.
  • Unlike encephalitic alphaviruses, CHIKV capsid protein does not inhibit host nuclear import.
  • Mutation of the NES in the CHIKV capsid protein (∆NES) blocked host protein access to the nucleus.

Conclusions:

  • CHIKV capsid protein undergoes CRM1-dependent nuclear export.
  • Nuclear targeting and export of CHIKV capsid protein are critical for its function.
  • While CHIKV capsid protein doesn't inhibit host nuclear import, its nuclear presence impacts nuclear transport.
  • Further research is needed to elucidate the complete interactions between CHIKV capsid protein and the host cell nucleus.

Related Concept Videos

Nuclear Export01:42

Nuclear Export

The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
5.0K
Nuclear Localization Signals and Import01:46

Nuclear Localization Signals and Import

Proteins targeted to the nucleus carry short stretches of amino acid sequences called the nuclear localization signal or NLS. Classical nuclear localization signals are of two types: monopartite and bipartite NLS. Monopartite classical NLS (cNLS) consists of a single cluster of 4-8 amino acids. Bipartite cNLS consists of two clusters of  2-3 amino acids and a 9-12 residue long proline-rich linker bridging the two clusters. Signal clusters are rich in positively charged amino acids such as...
7.9K
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
3.4K
Directionality of Nuclear Transport01:42

Directionality of Nuclear Transport

Ras-related nuclear protein or Ran is a small G protein that cycles between its GTP and GDP bound states. Ran specific regulators, a Ran GTPase Activating Protein or RanGAP present in the cytosol and a Ran guanine nucleotide exchange factor or RanGEF present inside the nucleus regulate GTP/GDP exchange. A high concentration of GTP inside the cells, in addition to this asymmetric distribution of  Ran-specific regulators, leads to a higher RanGTP concentration inside the nucleus. This...
4.7K
Nuclear Export of mRNA02:31

Nuclear Export of mRNA

Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
8.9K
Nuclear Export of mRNA02:31

Nuclear Export of mRNA

5.5K