Biology subjects

Mozzi, A.

Publications and source records attributed to Mozzi, A..

3 recordsLinked to original sources

bioRxiv2022

SARS-CoV-2 ORF3c impairs mitochondrial respiratory metabolism, oxidative stress and autophagic flow

Coronaviruses encode a variable number of accessory proteins that play a role in host-virus interactions, in the suppression of immune responses, or in immune evasion. Accessory proteins in SARS-CoV-2 consist of at least twelve viral proteins whose roles during infection have been extensively studied. Nevertheless, the role of the ORF3c accessory protein, an alternative open reading frame of ORF3a, has remained elusive. Herein, we characterized ORF3c in terms of cellular localization, hosts antiviral response modulation, and effects on mitochondrial metabolism. We show that ORF3c has a mitochondrial localization and alters mitochondrial metabolism, resulting in increased ROS production, block of the autophagic flux, and accumulation of autophagosomes/autolysosomes. Notably, we also found that ORF3c induces a shift from glucose to fatty acids oxidation and enhanced oxidative phosphorylation. This is similar to the condition observed in the chronic degenerative phase of COVID-19. Altogether these data suggest that ORF3c could be a key protein for SARS-CoV-2 pathogenesis and that it may play a role in disease progression.

microbiology↗

bioRxiv2020

Simplexviruses successfully adapt to their host by fine-tuning immune responses

Primate herpes simplex viruses are relatively harmless to their natural hosts, whereas cross-species transmission can result in severe disease. We performed a genome-wide scan for signals of adaptation of simplexviruses to hominins. We found evidence of positive selection in three glycoproteins, with selected sites located in antigenic determinants. Positively selected non-core proteins were involved in different immune-escape mechanisms. By expressing mutants of one of these proteins (ICP47), we show that the amino acid status at the positively selected sites is sufficient to induce HLA-G. HSV-1/HSV-2 ICP47 induced HLA-G when mutated to recapitulate residues in B virus, whereas the mutated version of B virus ICP47 failed to determine HLA-G expression. Thus, the evolution of ICP47 in HSV-1/HSV-2 determined the loss of an immunosuppressive effect, suggesting that simplexviruses tune immune responses to promote successful co-existence with their hosts. These results also help explain the high pathogenicity of B virus in humans.

microbiology↗

bioRxiv2020

Antigenic variation of SARS-CoV-2 in response to immune pressure

The ongoing evolution of SARS-CoV-2 is expected to be at least partially driven by the selective pressure imposed by the human immune system. We exploited the availability of a large number of high-quality SARS-CoV-2 genomes, as well as of validated epitope predictions, to show that B cell epitopes in the spike glycoprotein (S) and in the nucleocapsid protein (N) have higher diversity than non-epitope positions. Similar results were obtained for other human coronaviruses. Conversely, in the SARS-CoV-2 population, epitopes for CD4+ and CD8+ T cells were not more variable than non-epitope positions. A significant reduction in epitope variability was instead observed for some of the most immunogenic proteins (S, N, ORF8, and ORF3a). Analysis over longer evolutionary time-frames indicated that this effect is not due to differential constraints. These data indicate that SARS-CoV-2 is evolving to elude the host humoral immune response, whereas recognition by T cells might benefit the virus.

microbiology↗