Viruses from the family Iflaviridae are insect pathogens. Many of them, including slow bee paralysis virus (SBPV), cause lethal diseases in honeybees and bumblebees, resulting in agricultural losses. Iflaviruses have nonenveloped icosahedral virions containing single-stranded RNA genomes. However, their genome release mechanism is unknown. Here, we show that low pH promotes SBPV genome release, indicating that the virus may use endosomes to enter host cells. We used cryo-EM to study a heterogeneous population of SBPV virions at pH 5.5. We determined the structures of SBPV particles before and after genome release to resolutions of 3.3 and 3.4 Å, respectively. The capsids of SBPV virions in low pH are not expanded. Thus, SBPV does not appear to form "altered" particles with pores in their capsids before genome release, as is the case in many related picornaviruses. The egress of the genome from SBPV virions is associated with a loss of interpentamer contacts mediated by N-terminal arms of VP2 capsid proteins, which result in the expansion of the capsid. Pores that are 7 Å in diameter form around icosahedral threefold symmetry axes. We speculate that they serve as channels for the genome release. Our findings provide an atomic-level characterization of the genome release mechanism of iflaviruses.
- MeSH
- Dicistroviridae genetika fyziologie ultrastruktura MeSH
- elektronová kryomikroskopie MeSH
- genom virový MeSH
- kapsida ultrastruktura MeSH
- koncentrace vodíkových iontů MeSH
- konformace proteinů MeSH
- molekulární modely MeSH
- Picornaviridae genetika fyziologie ultrastruktura MeSH
- statická elektřina MeSH
- svlékání virového obalu fyziologie MeSH
- včely virologie MeSH
- virové plášťové proteiny chemie ultrastruktura MeSH
- viry hmyzu genetika fyziologie ultrastruktura MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Enteroviruses rank among the most common human pathogens; millions of people suffer from diseases caused by them every year. However, no specific treatment of infections caused by this genus from the Picornaviridae family has been introduced to clinical practice so far. Therefore, a search for potential therapeutics aiming at these viruses is urgently needed. Due to advances in biochemistry and molecular biology, we are able to aim at specific viral proteins as well as possible host factors essential for virus replication in cells. Recently, a number of compounds inhibiting replication of various enteroviruses have been reported, based on both rational targetbased drug design and phenotypic screening. This article is a review of common structure patterns of the compounds that have been recently found to inhibit the replication of enteroviruses.
- MeSH
- antivirové látky farmakokinetika farmakologie chemie klasifikace MeSH
- Enterovirus fyziologie genetika růst a vývoj účinky léků ultrastruktura MeSH
- inhibitory proteas chemie MeSH
- klinická farmakologie metody trendy MeSH
- lidé MeSH
- Picornaviridae * fyziologie genetika růst a vývoj účinky léků ultrastruktura MeSH
- pikornavirové infekce * farmakoterapie genetika MeSH
- replikace viru účinky léků MeSH
- virové plášťové proteiny * antagonisté a inhibitory účinky léků MeSH
- Check Tag
- lidé MeSH
