Abstract
The Caliciviridae are a family of viruses with a single-stranded, non-segmented RNA genome of positive polarity. The ongoing discovery of caliciviruses has increased the number of genera in this family to 11 (Norovirus, Nebovirus, Sapovirus, Lagovirus, Vesivirus, Nacovirus, Bavovirus, Recovirus, Salovirus, Minovirus, and Valovirus). Caliciviruses infect a wide range of hosts that include fishes, amphibians, reptiles, birds, and marine and land mammals. All caliciviruses have a genome that encodes a major and a minor capsid protein, a genome-linked viral protein, and several non-structural proteins. Of these non-structural proteins, only the helicase, protease, and RNA-dependent RNA polymerase share clear sequence and structural similarities with proteins from other virus families. In addition, all caliciviruses express two or three non-structural proteins for which functions have not been clearly defined. The sequence diversity of these non-structural proteins and a multitude of processing strategies suggest that at least some have evolved independently, possibly to counteract innate and adaptive immune responses in a host-specific manner. Studying these proteins is often difficult as many caliciviruses cannot be grown in cell culture. Nevertheless, the study of recombinant proteins has revealed many of their properties, such as intracellular localization, capacity to oligomerize, and ability to interact with viral and/or cellular proteins; the release of non-structural proteins from transfected cells has also been investigated. Here, we will summarize these findings and discuss recent in silico studies that identified previously overlooked putative functional domains and structural features, including transmembrane domains that suggest the presence of viroporins.
Highlights
The Caliciviridae family of RNA viruses currently includes 11 genera, i.e., Norovirus, Nebovirus, Sapovirus, Lagovirus, Vesivirus, Nacovirus, Bavovirus, Recovirus, Salovirus, Minovirus, and Valovirus (Desselberger, 2019; Vinjé et al, 2019)
Valoviruses were first isolated from the feces of asymptomatic farmed pigs; these viruses were named St-Valérien-like viruses and found to be closely related to noroviruses and recoviruses (L’Homme et al, 2009)
A similar protein-protein interaction has been found for NS1/2 of Murine norovirus (MNV) and VAP-A (McCune et al, 2017). These findings suggest that manipulating VAP-A might be an important strategy in the calicivirus life cycle
Summary
The Caliciviridae family of RNA viruses currently includes 11 genera, i.e., Norovirus, Nebovirus, Sapovirus, Lagovirus, Vesivirus, Nacovirus, Bavovirus, Recovirus, Salovirus, Minovirus, and Valovirus (Desselberger, 2019; Vinjé et al, 2019). Picornaviridae and Caliciviridae are closely related families of the order Picornavirales, which comprises non-enveloped viruses with a positive-sense RNA genome Both virus families direct host cells to synthesize a polyprotein that is cleaved by viral proteases, a process that, in some caliciviruses, is assisted by cellular proteases (Thumfart and Meyers, 2002; Sosnovtsev et al, 2006). The functions of the calicivirus RdRp, protease, helicase, and VPg were identified based on sequence similarities to homologous proteins from picornaviruses and other positive-sense singlestranded RNA viruses (Neill, 1990; Lambden and Clarke, 1995; Clarke and Lambden, 1997). The recent introduction of the highly pathogenic RHDV2 to Australia quickly led to the emergence of recombinant lagoviruses that contain the capsid genes of RHDV2 and the non-structural protein coding sequences of non-pathogenic RCV strains that had been circulating in Australian rabbits for decades. In the case of Tulane virus, NS1/2 oligomers were detected by Western blotting of unboiled lysates from transfected cells that were separated under
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