Structure of Aichi Virus 1 and Its Empty Particle: Clues to Kobuvirus Genome Release Mechanism

Abstract

Aichi virus 1 (AiV-1) is a human pathogen from the Kobuvirus genus of the Picornaviridae family. Worldwide, 80 to 95% of adults have antibodies against the virus. AiV-1 infections are associated with nausea, gastroenteritis, and fever. Unlike most picornaviruses, kobuvirus capsids are composed of only three types of subunits: VP0, VP1, and VP3. We present here the structure of the AiV-1 virion determined to a resolution of 2.1 Å using X-ray crystallography. The surface loop puff of VP0 and knob of VP3 in AiV-1 are shorter than those in other picornaviruses. Instead, the 42-residue BC loop of VP0 forms the most prominent surface feature of the AiV-1 virion. We determined the structure of AiV-1 empty particle to a resolution of 4.2 Å using cryo-electron microscopy. The empty capsids are expanded relative to the native virus. The N-terminal arms of capsid proteins VP0, which mediate contacts between the pentamers of capsid protein protomers in the native AiV-1 virion, are disordered in the empty capsid. Nevertheless, the empty particles are stable, at least in vitro, and do not contain pores that might serve as channels for genome release. Therefore, extensive and probably reversible local reorganization of AiV-1 capsid is required for its genome release.IMPORTANCE Aichi virus 1 (AiV-1) is a human pathogen that can cause diarrhea, abdominal pain, nausea, vomiting, and fever. AiV-1 is identified in environmental screening studies with higher frequency and greater abundance than other human enteric viruses. Accordingly, 80 to 95% of adults worldwide have suffered from AiV-1 infections. We determined the structure of the AiV-1 virion. Based on the structure, we show that antiviral compounds that were developed against related enteroviruses are unlikely to be effective against AiV-1. The surface of the AiV-1 virion has a unique topology distinct from other related viruses from the Picornaviridae family. We also determined that AiV-1 capsids form compact shells even after genome release. Therefore, AiV-1 genome release requires large localized and probably reversible reorganization of the capsid.

Bacterial Stabilization of a Panel of Picornaviruses

“…(A) Structural models of picornaviruses. Structural comparisons were performed using EMDB accession numbers for each viral genus and topological distances from the center of the virion calculated from 135 Å (blue) to 155 Å (red), as indicated by the scale bar (22). Representative viruses for each genus are Aichi virus ( Kobuvirus ), CVB3 ( Enterovirus ), and Saffold virus ( Cardiovirus ).…”

“…Although Aichi virus is transmitted by the fecal-oral route, there are large sequence and structural differences between Aichi virus and other picornaviruses that may contribute to the different phenotype (Fig. 1A and B) (22, 23). Although a member of the Caliciviridae , human norovirus can bind to and is stabilized by bacteria that express certain histo-blood group antigens (24, 25).…”

Low prevalence of Aichi virus in molluscan shellfish samples from Galicia (NW Spain)

“…It is a virus with icosahedral morphology that presents a genome of about 8400-nucleotidelong single-stranded positive sense RNA with an unusual high C content. The genome contains one open reading frame encoding structural and nonstructural proteins (Yamashita et al 1998;Sasaki et al 2001;Reuter et al 2011;Zhu et al 2016;Sabin et al 2016).…”

Ancient gene duplications in RNA viruses revealed by protein tertiary structure comparisons

“…In most viruses belonging to the family Picornaviridae , the capsid genes are translated into a single polyprotein which is proteolytically cleaved into VP0, VP3 and VP1. VP0 is then self-cleaved into VP4 and VP2, except in the genera Kobuvirus and Parechovirus , in which the equivalent of VP4 remains as a N-terminal extension of VP2 ( Sabin et al 2016 ; Kalynych et al 2016a ). In other families, such as Dicistroviridae and Iflaviridae , VP4 is cleaved from the N-terminal region of VP3 ( Liljas et al 2002 ; Kalynych et al 2016b ).…”