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PMID:23657274

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Citation

Agrawal, T, Schu, P and Medigeshi, GR (2013) Adaptor protein complexes-1 and 3 are involved at distinct stages of flavivirus life-cycle. Sci Rep 3:1813

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.

Links

PubMed PMC3648799 Online version:10.1038/srep01813

Keywords

Adaptor Protein Complex 1/physiology; Adaptor Protein Complex 3/physiology; Animals; Blotting, Western; Cell Proliferation; Cells, Cultured; Cercopithecus 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

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:AP1AR

GO:0030121: AP-1 adaptor complex

ECO:0000315:

C

Figure 1. Flavivirus production in AP-1-deficient cells.

complete
CACAO 8957

HUMAN:AP1S3

GO:0030123: AP-3 adaptor complex

ECO:0000315:

C

Figure 5. Defective viral RNA replication in AP-3-deficient cells.

complete
CACAO 8959

See also

References

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