The interaction between claudin-1 and dengue viral prM/M protein for its entry.
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.
Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, United States; University of Alabama at Birmingham, Department of Medicine, Division of Infectious Diseases, BBRB 562, 845 19th Street South, Birmingham, AL 35294, United States.
Pulin
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Che
Hengli
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Tang
Qianjun
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Li
D002460:Cell Line; D002498:Centrifugation; D062445:Claudin-1 / Q000235:genetics / Q000378:metabolism*; D003716:Dengue Virus / Q000502:physiology*; D055785:Gene Knockdown Techniques; D054884:Host-Pathogen Interactions; D006801:Humans; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D017354:Point Mutation; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017384:Sequence Deletion; D014764:Viral Proteins / Q000378:metabolism*; D053586:Virus Internalization
D062445:Claudin-1; D050505:Mutant Proteins; D014764:Viral Proteins; C084187:prM protein, Dengue virus type 3
Claudin-1; Dengue virus; Extracellular loops; Tight junction; Virus entry; prM