The interaction between claudin-1 and dengue viral prM/M protein for its entry

Virology. 2013 Nov;446(1-2):303-13. doi: 10.1016/j.virol.2013.08.009. Epub 2013 Sep 7.

Abstract

Dengue disease is becoming a huge public health concern around the world as more than one-third of the world's population living in areas at risk of infection. In an effort to assess host factors interacting with dengue virus, we identified claudin-1, a major tight junction component, as an essential cell surface protein for dengue virus entry. When claudin-1 was knocked down in Huh 7.5 cells via shRNA, the amount of dengue virus entering host cells was reduced. Consequently, the progeny virus productions were decreased and dengue virus-induced CPE was prevented. Furthermore, restoring the expression of claudin-1 in the knockdown cells facilitated dengue virus entry. The interaction between claudin-1 and dengue viral prM protein was further demonstrated using the pull-down assay. Deletion of the extracellular loop 1 (ECL1) of claudin-1 abolished such interaction, so did point mutations C54A, C64A and I32M on ECL1. These results suggest that the interaction between viral protein prM and host protein claudin-1 was essential for dengue entry. Since host and viral factors involved in virus entry are promising therapeutic targets, determining the essential role of claudin-1 could lead to the discovery of entry inhibitors with attractive therapeutic potential against dengue disease.

Keywords: Claudin-1; Dengue virus; Extracellular loops; Tight junction; Virus entry; prM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Centrifugation
  • Claudin-1 / genetics
  • Claudin-1 / metabolism*
  • Dengue Virus / physiology*
  • Gene Knockdown Techniques
  • Host-Pathogen Interactions*
  • Humans
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism
  • Point Mutation
  • Protein Binding
  • Protein Interaction Mapping*
  • Sequence Deletion
  • Viral Proteins / metabolism*
  • Virus Internalization*

Substances

  • Claudin-1
  • Mutant Proteins
  • Viral Proteins
  • prM protein, Dengue virus type 3