Biology subjects

Cavazzini, D.

Publications and source records attributed to Cavazzini, D..

2 recordsLinked to original sources

bioRxiv2022

Characterization of BoHV-4 ORF45

Bovine herpesvirus 4 (BoHV-4) is a Gammaherpesvirus of the genus Rhadinovirus, his natural host is the bovine whereas the African Buffalo the natural reservoir. Anyhow, BoHV-4 infection is not associated to a specific disease. Genome structure and genes are well conserved in Gammaherpesvirus, and orf45 gene and its product, ORF45, is one of those. BoHV-4 ORF45 has been suggested to be a tegument protein, however, BoHV-4 ORF45 structure and function have not yet been experimentally characterized. In the present study, it is shown that BoHV-4 ORF45, despite its poor homology with other characterized Rhadinovirus ORF45s, is structurally related to Kaposis sarcoma-associated herpesvirus (KSHV), is a phosphoprotein and localizes in the host cell nuclei. Through the generation of an ORF45-null mutant BoHV-4 and its pararevertant, it was possible to demonstrate that ORF45 is essential for BoHV-4 lytic replication and is associated to the viral particles, as for the other characterized Rhadinovirus ORF45s. Finally, the impact of BoHV-4 ORF45 on cellular transcriptome was investigated, an aspect poorly explored or not at all for other Gammaherpesvirus. Many cellular transcriptional pathways were found to be alterate, mainly those involving p90 ribosomal S6 kinase (RSK) and signal-regulated kinase (ERK) complex (RSK/ERK), thus highlighting the authentic character of BoHV-4 ORF45 and paving the way to further investigations.

microbiology↗

bioRxiv2022

Natural heteroclitic-like peptides are generated by SARS-CoV-2 mutations

Mutations carried by SARS-CoV-2 spike protein variants may promote viral escape from immune protection. Humoral immunity is sensitive to evasion by SARS-CoV-2 mutants, but the impact of viral evolution on the interplay between virus and host CD8 T cell reactivity remains uncertain. By a systematic functional analysis of 30 spike variant mutations, we show that in vaccinated as well as convalescent subjects, mutated epitopes can have not only a neutral or abrogating effect on the recognition by CD8 T cells but can also enhance or even generate de novo CD8 T cell responses. Large pools of peptides spanning the entire spike sequence and comprising previously identified CD8 T cell epitopes were then used in parallel with variant peptides to define strength and multispecificity of total anti-spike CD8 responses. In some individuals, CD8 cells were narrowly focused on a few epitopes indicating that in this context of weak and oligospecific responses the overall antiviral protection can likely benefit of the function enhancing effect of heteroclitic-like mutations. In conclusion, appearance of mutated stimulatory epitopes likely reflects an epiphenomenon of SARS-CoV-2 evolution driven by antibody evasion and increased transmissibility, that might bear clinical relevance in a subset of individuals with weak and oligospecific CD8 T cell responses.

immunology↗