Autographa californica Multiple Nucleopolyhedrovirus Ac34 Protein Retains Cellular Actin-Related Protein 2/3 Complex in the Nucleus by Subversion of CRM1-Dependent Nuclear Export

PLoS Pathog. 2016 Nov 1;12(11):e1005994. doi: 10.1371/journal.ppat.1005994. eCollection 2016 Nov.

Abstract

Actin, nucleation-promoting factors (NPFs), and the actin-related protein 2/3 complex (Arp2/3) are key elements of the cellular actin polymerization machinery. With nuclear actin polymerization implicated in ever-expanding biological processes and the discovery of the nuclear import mechanisms of actin and NPFs, determining Arp2/3 nucleo-cytoplasmic shuttling mechanism is important for understanding the function of nuclear actin. A unique feature of alphabaculovirus infection of insect cells is the robust nuclear accumulation of Arp2/3, which induces actin polymerization in the nucleus to assist in virus replication. We found that Ac34, a viral late gene product encoded by the alphabaculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV), is involved in Arp2/3 nuclear accumulation during virus infection. Further assays revealed that the subcellular distribution of Arp2/3 under steady-state conditions is controlled by chromosomal maintenance 1 (CRM1)-dependent nuclear export. Upon AcMNPV infection, Ac34 inhibits CRM1 pathway and leads to Arp2/3 retention in the nucleus.

MeSH terms

  • Actin-Related Protein 2-3 Complex / metabolism*
  • Active Transport, Cell Nucleus / physiology*
  • Animals
  • Cell Nucleus / metabolism
  • Exportin 1 Protein
  • Fluorescent Antibody Technique
  • Immunoprecipitation
  • Karyopherins / metabolism*
  • Nucleopolyhedroviruses / metabolism*
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Sf9 Cells
  • Transfection
  • Viral Proteins / metabolism
  • Virus Replication / physiology*

Substances

  • Actin-Related Protein 2-3 Complex
  • Karyopherins
  • Receptors, Cytoplasmic and Nuclear
  • Viral Proteins

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (http://www.nsfc.gov.cn/) (31030027 and 31321001 to XC; 31470261 and 31270191 to YW). The Royal Dutch Academy of Science and Arts (08-PSA-BD-01 to MMvO) (https://www.knaw.nl/) is acknowledged for financing part of this research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.