Norovirus gene expression and replication

Thorne, Lucy; Goodfellow, Ian

doi:10.1099/vir.0.059634-0

Cited by 235 publications

(273 citation statements)

References 112 publications

(198 reference statements)

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“…Removal of the VPg protein by proteolytic treatment of viral RNA completely abolishes infectivity (46), indicating that the VPg protein may play a role in the recruitment of cellular translation initiation factors, analogous to what has been described for caliciviruses (73). The genome is then translated, giving rise to nsP1a1b and nsP1a polyproteins, which are then cleaved by the viral serine protease (in nsP1a) as well as some cellular proteases, resulting in the individual nonstructural proteins (Fig.…”

Section: Translation/replicationmentioning

confidence: 99%

Human Astroviruses

2014

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SUMMARY Human astroviruses (HAtVs) are positive-sense single-stranded RNA viruses that were discovered in 1975. Astroviruses infecting other species, particularly mammalian and avian, were identified and classified into the genera Mamastrovirus and Avastrovirus . Through next-generation sequencing, many new astroviruses infecting different species, including humans, have been described, and the Astroviridae family shows a high diversity and zoonotic potential. Three divergent groups of HAstVs are recognized: the classic ( MAstV 1 ), HAstV-MLB ( MAstV 6 ), and HAstV-VA/HMO ( MAstV 8 and MAstV 9 ) groups. Classic HAstVs contain 8 serotypes and account for 2 to 9% of all acute nonbacterial gastroenteritis in children worldwide. Infections are usually self-limiting but can also spread systemically and cause severe infections in immunocompromised patients. The other groups have also been identified in children with gastroenteritis, but extraintestinal pathologies have been suggested for them as well. Classic HAstVs may be grown in cells, allowing the study of their cell cycle, which is similar to that of caliciviruses. The continuous emergence of new astroviruses with a potential zoonotic transmission highlights the need to gain insights on their biology in order to prevent future health threats. This review focuses on the basic virology, pathogenesis, host response, epidemiology, diagnostic assays, and prevention strategies for HAstVs.

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Section: Translation/replicationmentioning

confidence: 99%

Human Astroviruses

2014

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“…The genome is covalently linked to the viral protein genome (VPg) at the 5= end and polyadenylated at the 3= end (17). There are three open reading frames (ORFs), designated ORF-1, ORF-2, and ORF-3, encoding eight viral proteins (Fig.…”

Section: Basic Virology and Viral Diversitymentioning

confidence: 99%

“…Hence, calici is derived from the Latin word calyx, or "cup" (16). ORF-1 encodes a polyprotein that is proteolytically processed into the 6 nonstructural proteins, including the norovirus protease and RNA-dependent RNA polymerase (17).…”

Section: Basic Virology and Viral Diversitymentioning

confidence: 99%

Norovirus

2015

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SUMMARY Norovirus, an RNA virus of the family Caliciviridae , is a human enteric pathogen that causes substantial morbidity across both health care and community settings. Several factors enhance the transmissibility of norovirus, including the small inoculum required to produce infection (<100 viral particles), prolonged viral shedding, and its ability to survive in the environment. In this review, we describe the basic virology and immunology of noroviruses, the clinical disease resulting from infection and its diagnosis and management, as well as host and pathogen factors that complicate vaccine development. Additionally, we discuss overall epidemiology, infection control strategies, and global reporting efforts aimed at controlling this worldwide cause of acute gastroenteritis. Prompt implementation of infection control measures remains the mainstay of norovirus outbreak management.

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“…1A). All members of the Caliciviridae family of small positive-sense RNA viruses synthesize a shorter-than-genome-length, subgenomic RNA (sgRNA) which directs the translation of the major and minor structural proteins, VP1 and VP2, respectively (10). The MNV sgRNA also encodes the VF1 protein, an antagonist of the innate immune response (12).…”

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confidence: 99%

The Murine Norovirus Core Subgenomic RNA Promoter Consists of a Stable Stem-Loop That Can Direct Accurate Initiation of RNA Synthesis

Yunus

Lin

Bailey

et al. 2015

J Virol

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All members of the Caliciviridae family of viruses produce a subgenomic RNA during infection. The subgenomic RNA typically encodes only the major and minor capsid proteins, but in murine norovirus (MNV), the subgenomic RNA also encodes the VF1 protein, which functions to suppress host innate immune responses. To date, the mechanism of norovirus subgenomic RNA synthesis has not been characterized. We have previously described the presence of an evolutionarily conserved RNA stem-loop structure on the negative-sense RNA, the complementary sequence of which codes for the viral RNA-dependent RNA polymerase (NS7). The conserved stem-loop is positioned 6 nucleotides 3= of the start site of the subgenomic RNA in all caliciviruses. We demonstrate that the conserved stem-loop is essential for MNV viability. Mutant MNV RNAs with substitutions in the stem-loop replicated poorly until they accumulated mutations that revert to restore the stem-loop sequence and/or structure. The stem-loop sequence functions in a noncoding context, as it was possible to restore the replication of an MNV mutant by introducing an additional copy of the stem-loop between the NS7-and VP1-coding regions. Finally, in vitro biochemical data suggest that the stem-loop sequence is sufficient for the initiation of viral RNA synthesis by the recombinant MNV RNA-dependent RNA polymerase, confirming that the stem-loop forms the core of the norovirus subgenomic promoter. IMPORTANCENoroviruses are a significant cause of viral gastroenteritis, and it is important to understand the mechanism of norovirus RNA synthesis. Here we describe the identification of an RNA stem-loop structure that functions as the core of the norovirus subgenomic RNA promoter in cells and in vitro. This work provides new insights into the molecular mechanisms of norovirus RNA synthesis and the sequences that determine the recognition of viral RNA by the RNA-dependent RNA polymerase. N oroviruses, members of the Caliciviridae family of small positive-sense RNA viruses, are a major cause of viral gastroenteritis in the developed world (1, 2). Despite their impact, noroviruses remain poorly characterized, as an in-depth understanding of the molecular mechanisms of norovirus genome translation and replication has been hampered by the inability to culture human norovirus (3). Murine norovirus (MNV) is a model system with which to understand the norovirus life cycle (4), as it replicates in cultured cells (5) and a number of tractable reverse genetics systems are available (6-9). Studies of MNV have therefore led to a number of significant advances in the understanding of the molecular mechanism of norovirus genome translation and replication (reviewed in reference 10).The norovirus RNA genome typically carries three open reading frames (ORFs) (11). MNV also has an additional ORF in the region overlapping the VP1-coding region (12, 13) (Fig. 1A). All members of the Caliciviridae family of small positive-sense RNA viruses synthesize a shorter-than-genome-length, subgenomic RNA (sgRNA)...

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Norovirus gene expression and replication

Cited by 235 publications

References 112 publications

Human Astroviruses

Human Astroviruses

Norovirus

The Murine Norovirus Core Subgenomic RNA Promoter Consists of a Stable Stem-Loop That Can Direct Accurate Initiation of RNA Synthesis

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