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
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Protein Complex 1 / physiology*
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Adaptor Protein Complex 3 / physiology*
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Animals
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Blotting, Western
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Cell Proliferation
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Cells, Cultured
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Chlorocebus aethiops
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Cricetinae
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Dengue / metabolism
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Dengue / pathology
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Dengue / virology
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Dengue Virus / physiology
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Embryo, Mammalian / cytology
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Embryo, Mammalian / metabolism
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Embryo, Mammalian / virology
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Encephalitis Virus, Japanese / physiology
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Encephalitis, Japanese / metabolism
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Encephalitis, Japanese / pathology
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Encephalitis, Japanese / virology
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Fibroblasts / cytology
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Fibroblasts / metabolism
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Fibroblasts / virology
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Flavivirus / physiology*
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Flavivirus Infections / metabolism*
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Flavivirus Infections / pathology
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Flavivirus Infections / virology
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Fluorescent Antibody Technique
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Kidney / cytology
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Kidney / metabolism
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Kidney / virology
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Mice
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Mice, Knockout
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RNA, Messenger / genetics
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RNA, Viral / genetics
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Real-Time Polymerase Chain Reaction
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Reverse Transcriptase Polymerase Chain Reaction
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Vero Cells
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Virus Replication*
Substances
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Adaptor Protein Complex 1
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Adaptor Protein Complex 3
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RNA, Messenger
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RNA, Viral