Valeria Lulla

@valerialulla.bsky.social

PI Virologist & Wellcome Trust/Royal Society Sir Henry Dale fellow studying RNA viruses at the University of Cambridge

🚨 New paper from the lab! 🚀 We explore “The dynamics and strategy of RNA replication in astroviruses”, now out in NAR Molecular Medicine. Many thanks to all co-authors and congratulations to David Noyvert on his first first-author paper🎉 doi.org/10.1093/narm...

The dynamics and strategy of RNA replication in astroviruses

Abstract. Astroviruses are positive-sense single-stranded RNA viruses that cause significant disease across avian and mammalian hosts, yet their replicatio

doi.org

#JGV is recruiting a new Editor for positive-strand RNA viruses. If you’re interested in contributing to the journal and the field, I’d be happy to share my editorial experience - please get in touch!

Post nicht verfügbar.

📢How do astroviruses replicate their RNA genome? Led by a talented PhD student in the lab, David Noyvert, this story identifies novel (-)sgRNA species, shows terminal features of viral RNAs, and uncovers the secret life of RNA replication dynamics and packaging! www.biorxiv.org/content/10.6...

The dynamics and strategy of RNA replication in astroviruses

Astroviruses are positive-sense single-stranded RNA viruses that cause significant disease across avian and mammalian hosts, yet their replication mechanisms remain poorly understood. The replication of astrovirus RNA occurs via a double-stranded RNA intermediate that is used as a template for the synthesis of new positive-sense RNA, which is covalently linked to the virus-encoded protein VPg. These viruses also produce a capsid-encoding subgenomic (sg) RNA that is 3′-coterminal with the genomic RNA. The mechanisms by which the astrovirus sgRNA is produced and regulated during infection have not yet been characterized. Using high throughput sequencing of RNA from cells infected with each of five different astrovirus strains, we demonstrate that the presence of a (−)sgRNA is a conserved feature of infection, supporting a premature termination model of subgenomic RNA production. A pronounced pile-up in the mapping positions of the 3ʹ ends of negative-sense RNA reads marks the precise 3ʹ terminus of the (−)sgRNA. We investigate the relative abundance and dynamics of positive and negative RNA species during virus replication and virion packaging, and perform a mutational analysis of conserved residues in the genomic and subgenomic 5ʹ termini. Together, this work elucidates the dynamics of genomic and subgenomic RNA synthesis during astrovirus infection. ### Competing Interest Statement The authors have declared no competing interest. Wellcome Trust, https://ror.org/029chgv08, 220620/Z/20/Z, 220814/Z/20/Z

biorxiv.org

How does fever work? Our new Science paper shows how elevated body temperature can protect against severe influenza and that avian-origin viruses escape this defence. This is likely one reason why bird flus and some pandemic influenzas can be so severe.🧵 www.science.org/doi/10.1126/...

Avian-origin influenza A viruses tolerate elevated pyrexic temperatures in mammals

Host body temperature can define a virus’s replicative profile—influenza A viruses (IAVs) adapted to 40° to 42°C in birds are less temperature sensitive in vitro compared with human isolates adapted t...

science.org

📢Astrovirus polyprotein processing is finally uncovered - these viruses use peculiar dual cleavage sites around their protease! Led by a talented PhD student, David Noyvert, this work provides a map of astrovirus genomes. Great collaboration with @emmottlab.bsky.social @leandroxneves.bsky.social

Viral protease-mediated polyprotein processing in human astroviruses

Positive-sense RNA viruses often encode large polyproteins that are proteolytically processed by viral and host proteases into functional replication proteins. Astroviruses infect intestinal and neuro...

biorxiv.org

📢Enteroviruses can have two upstream ORFs, and both can be translated! Led by Rhian O’Connor, this work shows the remarkable flexibility of enterovirus genomes and the advantage of double-uAUG virus in terminally differentiated cells – intestinal organoids and neurons www.biorxiv.org/content/10.1...

Flexibility and modulation of translation initiation in enterovirus genomes

Enteroviruses comprise a large group of mammalian pathogens that often utilize two open reading frames (ORFs) to encode their proteins: the upstream protein (UP) and the main polyprotein. In some enteroviruses, in addition to the canonical upstream AUG (uAUG), there is another AUG that may represent an alternative upstream initiation site. An analysis of enterovirus sequences containing additional upstream AUGs identified several clusters, including strains of pathogenic Enterovirus alphacoxsackie and E. coxsackiepol. Using ribosome profiling on coxsackievirus CVA-13 (E. coxsackiepol), we demonstrate that both upstream AUG codons can be used for translation initiation in infected cells. Moreover, we confirm translation from both upstream AUGs using a reporter system. Mutating the additional upstream AUG in the context of CVA-13 did not result in phenotypic changes in immortalized cell lines. However, the wild-type virus outcompeted this mutant in human intestinal organoids and differentiated neuronal systems, representing an advantage in physiologically relevant infection sites. Mutation of the stop codon of the shorter upstream ORF led to dysregulated translation of the other ORFs in the reporter system, suggesting a potential role for the additional uORF in modulating the expression level of the other ORFs. These findings demonstrate the remarkable plasticity of enterovirus IRES-mediated initiation and the competitive advantage of double-upstream-AUG-containing viruses in terminally differentiated intestinal organoids and neuronal systems. ### Competing Interest Statement The authors have declared no competing interest.

biorxiv.org

Excited to share our first preprint of 2024!🎉 In astroviruses, the N-terminal domain of nonstructural protein drives the formation of replication complexes in tight association with perinuclear ER membranes. Great work by Hashim and colleagues!

The astrovirus N-terminal nonstructural protein anchors replication complexes to the perinuclear ER ...

bioRxiv - the preprint server for biology, operated by Cold Spring Harbor Laboratory, a research and educational institution

doi.org