Adaptor protein complexes-1 and 3 are involved at distinct stages of flavivirus life-cycle

Sci Rep. 2013:3:1813. doi: 10.1038/srep01813.

Abstract

Intracellular protein trafficking pathways are hijacked by viruses at various stages of viral life-cycle. Heterotetrameric adaptor protein complexes (APs) mediate vesicular trafficking at distinct intracellular sites and are essential for maintaining the organellar homeostasis. In the present study, we studied the effect of AP-1 and AP-3 deficiency on flavivirus infection in cells functionally lacking these proteins. We show that AP-1 and AP-3 participate in flavivirus life-cycle at distinct stages. AP-3-deficient cells showed delay in initiation of Japanese encephalitis virus and dengue virus RNA replication, which resulted in reduction of infectious virus production. AP-3 was found to colocalize with RNA replication compartments in infected wild-type cells. AP-1 deficiency affected later stages of dengue virus infection where increased intracellular accumulation of infectious virus was observed. Therefore, our results propose a novel role for AP-1 and AP-3 at distinct stages of infection of some of the RNA viruses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Protein Complex 1 / physiology*
  • Adaptor Protein Complex 3 / physiology*
  • Animals
  • Blotting, Western
  • Cell Proliferation
  • Cells, Cultured
  • Chlorocebus aethiops
  • Cricetinae
  • Dengue / metabolism
  • Dengue / pathology
  • Dengue / virology
  • Dengue Virus / physiology
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / metabolism
  • Embryo, Mammalian / virology
  • Encephalitis Virus, Japanese / physiology
  • Encephalitis, Japanese / metabolism
  • Encephalitis, Japanese / pathology
  • Encephalitis, Japanese / virology
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Fibroblasts / virology
  • Flavivirus / physiology*
  • Flavivirus Infections / metabolism*
  • Flavivirus Infections / pathology
  • Flavivirus Infections / virology
  • Fluorescent Antibody Technique
  • Kidney / cytology
  • Kidney / metabolism
  • Kidney / virology
  • Mice
  • Mice, Knockout
  • RNA, Messenger / genetics
  • RNA, Viral / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vero Cells
  • Virus Replication*

Substances

  • Adaptor Protein Complex 1
  • Adaptor Protein Complex 3
  • RNA, Messenger
  • RNA, Viral