Abstract
Enterovirus 71 is one of the major causative agents of hand, foot, and mouth disease in infants and children. Replication of enterovirus 71 depends on host cellular factors. The viral replication complex is formed in novel, cytoplasmic, vesicular compartments. It has not been elucidated which cellular pathways are hijacked by the virus to create these vesicles. Here, we investigated whether proteins associated with the cellular secretory pathway were involved in enterovirus 71 replication. We used a loss-of-function assay, based on small interfering RNA. We showed that enterovirus 71 RNA replication was dependent on the activity of Class I ADP-ribosylation factors. Simultaneous depletion of ADP-ribosylation factors 1 and 3, but not three others, inhibited viral replication in cells. We also demonstrated with various techniques that the brefeldin-A-sensitive guanidine nucleotide exchange factor, GBF1, was critically important for enterovirus 71 replication. Our results suggested that enterovirus 71 replication depended on GBF1-mediated activation of Class I ADP-ribosylation factors. These results revealed a connection between enterovirus 71 replication and the cellular secretory pathway; this pathway may represent a novel target for antiviral therapies.
Highlights
Enterovirus 71 (EV71) is a member of the genus Enterovirus in the family of Picornaviridae
We previously showed that cellular complex I (COPI) activity was required for EV71 replication in rhabdomyosarcoma (RD) cells [11]
The membrane-bound form of Class I ADP-ribosylation factor (Arf) increased substantially with EV71 infection. These results indicated that Class I Arfs were upregulated and activated upon an EV71 infection
Summary
Enterovirus 71 (EV71) is a member of the genus Enterovirus in the family of Picornaviridae. EV71 infections are known to cause hand, foot, and mouth disease. Some severe cases may present with serious neurological symptoms, such as aseptic meningitis, encephalitis, and acute flaccid paralysis; infections may lead to death [1,2]. EV71 has a ,7.4 kb, positivesense, single-stranded RNA genome. The genome comprises a single open reading frame that encodes a polyprotein, flanked by 59- and 39-untranslated regions (UTRs). The translated polyprotein is cleaved in both cis and trans processes that involve virusencoded proteases, 2Apro, 3Cpro, and 3CDpro. The cleavages produce about 10 final products and several cleavage intermediates
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