The interaction of flavivirus M protein with light chain Tctex-1 of human dynein plays a role in late stages of virus replication

Virology. 2011 Sep 1;417(2):369-78. doi: 10.1016/j.virol.2011.06.022. Epub 2011 Jul 20.

Abstract

The role of the membrane protein (prM/M) in flavivirus life cycle remains unclear. Here, we identified a cellular interactor to the 40-residue-long ectodomain of prM/M (ectoM) using a yeast two-hybrid screen against a human cDNA library and GST pull-down assays. We showed that dynein light chain Tctex-1 interacts with the ectoM of dengue 1-4, West Nile, and Japanese encephalitis flaviviruses. No interaction was found with yellow fever and tick-borne flaviviruses. This interaction is highly specific since a single amino-acid change in the ectoM abrogates the interaction with Tctex-1. To understand the role of this interaction, silencing of Tctex-1 using siRNA was performed prior to infection. A significant decrease in progeny production was observed for dengue and West Nile viruses. Silencing Tctex-1 inhibited the production of recombinant dengue subviral particles (RSPs). Thus Tctex-1 may play a role in late stages of viral replication through its interaction with the membrane protein.

MeSH terms

  • Dengue Virus / physiology*
  • Dyneins / genetics
  • Dyneins / metabolism*
  • Encephalitis Virus, Japanese / physiology*
  • Gene Silencing
  • Host-Pathogen Interactions
  • Humans
  • Protein Interaction Mapping*
  • RNA, Small Interfering / metabolism
  • Two-Hybrid System Techniques
  • Viral Envelope Proteins / metabolism*
  • Virus Replication*
  • West Nile virus / physiology*

Substances

  • RNA, Small Interfering
  • Viral Envelope Proteins
  • prM protein, Flavivirus
  • Dyneins