pelo is required for high efficiency viral replication

PLoS Pathog. 2014 Apr 10;10(4):e1004034. doi: 10.1371/journal.ppat.1004034. eCollection 2014 Apr.

Abstract

Viruses hijack host factors for their high speed protein synthesis, but information about these factors is largely unknown. In searching for genes that are involved in viral replication, we carried out a forward genetic screen for Drosophila mutants that are more resistant or sensitive to Drosophila C virus (DCV) infection-caused death, and found a virus-resistant line in which the expression of pelo gene was deficient. Our mechanistic studies excluded the viral resistance of pelo deficient flies resulting from the known Drosophila anti-viral pathways, and revealed that pelo deficiency limits the high level synthesis of the DCV capsid proteins but has no or very little effect on the expression of some other viral proteins, bulk cellular proteins, and transfected exogenous genes. The restriction of replication of other types of viruses in pelo deficient flies was also observed, suggesting pelo is required for high level production of capsids of all kinds of viruses. We show that both pelo deficiency and high level DCV protein synthesis increase aberrant 80S ribosomes, and propose that the preferential requirement of pelo for high level synthesis of viral capsids is at least partly due to the role of pelo in dissociation of stalled 80S ribosomes and clearance of aberrant viral RNA and proteins. Our data demonstrated that pelo is a host factor that is required for high efficiency translation of viral capsids and targeting pelo could be a strategy for general inhibition of viral infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Capsid / metabolism
  • Dicistroviridae / physiology*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster
  • Gene Expression Regulation, Viral / physiology*
  • Mutation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Biosynthesis / physiology*
  • Viral Proteins / biosynthesis*
  • Viral Proteins / genetics
  • Virus Replication / physiology*

Substances

  • Drosophila Proteins
  • Nuclear Proteins
  • Viral Proteins
  • pelo protein, Drosophila

Grant support

This work was supported by the National Basic Research Program of China (973 Program; 2013CB944903 and 2014CB541804), the National Natural Science Foundation of China (31330047, 91029304 and 31221065), the Hi-Tech Research and Development Program of China (863 program; 2012AA02A201), the 111 Project (B12001), and the Open Research Fund of State Key Laboratory of Cellular Stress Biology, Xiamen University (SKLCSB2012KF003). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.