Biology subjects

Ciccozzi, M.

Publications and source records attributed to Ciccozzi, M..

8 recordsLinked to original sources

bioRxiv2024

From North to South: Transmission Dynamics of H1N1pdm09 Swine Influenza A Viruses in Italy

The influenza A H1N1pdm09 virus continues to be a significant pathogen, posing potential risks to both animal and human health due to its zoonotic potential. Italy, which has one of the largest swine populations in Europe, plays a crucial role in monitoring the evolution of influenza viruses in livestock. This study aims to address the existing knowledge gaps regarding the genetic diversity and transmission dynamics of H1N1pdm09 circulating in Italian swine populations. Utilizing whole genome sequencing and dynamic modeling, we conducted a comprehensive analysis of virus samples collected from swine farms across Italy. Our results reveal that multiple independent viral introductions have occurred into the country, with most cases resulting in self-limited infections and limited onward transmission. However, six distinct transmission clusters were identified, suggesting instances of sustained viral spread. These clusters were found across multiple regions of Italy, highlighting the broad geographic distribution of virus lineages. Our findings indicate that while many introductions led to localized containment, certain virus lineages were able to spread within specific regions of Italy. Through a detailed examination of selective pressures, we observed that most viral genes are under strong purifying selection in both swine and human hosts, as reflected by dN/dS ratios well below 1. The hemagglutinin (HA) gene exhibited a notably higher dN/dS ratio in swine ([~]0.28) compared to humans ([~]0.22), indicating slightly relaxed selection in swine. In contrast, other genes, such as neuraminidase (NA) and non-structural protein (NS), showed similarly strong purifying selection across both hosts. These results reflect a general trend of selective pressures affecting multiple viral components, rather than emphasizing specific genes. Our study emphasizes the importance of ongoing genomic surveillance in detecting viral circulation and mitigating risks to both animal and public health. Italys efforts contribute significantly to global influenza monitoring and highlight the importance of a One Health approach that integrates human, animal, and environmental health. These findings provide essential data to inform public health policies and enhance preparedness against future zoonotic influenza outbreaks.

microbiology↗

bioRxiv2022

Genome-based comparison between the recombinant SARS-CoV-2 XBB and its parental lineages

Recombination is the main contributor to RNA virus evolution, and SARS-CoV-2 during the pandemic produced several recombinants. The most recent SARS-CoV-2 recombinant is the lineage labeled XBB, also known as Gryphon, which arose from BJ.1 and BM. 1.1.1. Here we performed a genome-based survey aimed to compare the new recombinant with its parental lineages that never became dominant. Genetic analyses indicated that the recombinant XBB and its first descendant XBB.1 show an evolutionary condition typical of an evolutionary blind background with no further epidemiologically relevant descendant. Genetic variability and expansion capabilities are slightly higher than parental lineages. Bayesian Skyline Plot indicates that XBB reached its plateau around October 6, 2022 and after an initial rapid growth the viral population size did not further expand, and around November 10, 2022 its levels of genetic variability decreased. Simultaneously with the reduction of the XBB population size, an increase of the genetic variability of its first sub-lineage XBB.1 occurred, that in turn reached the plateau around November 9, 2022 showing a kind of vicariance with its direct progenitors. Structure analysis indicates that the affinity for ACE2 surface in XBB/XBB.1 RBDs is weaker than for BA.2 RBD. In conclusion, nowadays XBB and XBB.1 do not show evidence about a particular danger or high expansion capability. Genome-based monitoring must continue uninterrupted in order to individuate if further mutations can make XBB more dangerous or generate new subvariants with different expansion capability.

genetics↗

bioRxiv2022

Genetic and structural data on the SARS-CoV-2 Omicron BQ.1 variant reveal its low potential for epidemiological expansion

The BQ.1 SARS-CoV-2 variant, also known as Cerberus, is one of the most recent Omicron descendant lineages. Compared to its direct progenitor BA.5, BQ.1 carries out some additional spike mutations in some key antigenic site which confer it further immune escape ability over other circulating lineage. In such a context, here we performed a genome-based survey aimed to obtain an as complete as possible nuance of this rapidly evolving Omicron subvariant. Genetic data suggests that BQ.1 represents an evolutionary blind background, lacking of the rapid diversification which is typical of a dangerous lineage. Indeed, the evolutionary rate of BQ.1 is very similar to that of BA.5 (7.6 x 10-4 and 7 x 10-4 subs/site/year, respectively), which is circulating by several months. Bayesian Skyline Plot reconstruction, indicates low level of genetic variability, suggesting that the peak has been reached around September 3, 2022. Structure analyses performed by comparing the properties of BQ.1 and BA.5 RBD indicated that the impact of the BQ.1 mutations on the affinity for ACE2 may be modest. Likewise, immunoinformatic analyses showed modest differences between the BQ.1 and the BA5 potential B-cells epitope. In conclusion, genetic and structural analysis on SARS-CoV-2 BQ.1 suggest that, it does not show evidence about its particular dangerous or high expansion capability. The monitoring genome-based must continue uninterrupted for a better understanding of its descendant and all other lineages.

molecular biology↗

bioRxiv2022

The evolution of Monkeypox virus: a genetic and structural analysis reveals mutations in proteins involved in host-pathogen interaction

BackgroundOver the past few months, we have witnessed a new outbreak of a MPXV that has been detected without a clear link to Africa and has quickly spread globally. MethodsIn this article we investigate the mutational pattern of the MPXV and provide evidence for the presence of 6 new mutations that appear to characterize the current MPX-2022 outbreak. With the use of a number of chemical and physical parameters, we predict the stability of the mutated proteins, and propose an interpretation of the impact of these mutations on viral fitness). FindingsMost mutations, particularly the Immunomodulator A46, TNFr and Large transcript constituent, affect proteins playing an important role in host response to MPVX infection and could also be relevant to the clinical features of the 2022 MPXV outbreak. InterpretationAlthough further, experimental work is necessary for a full understanding of the impact of the mutations here reported on virus replication pathways and host immunomodulation, our in-silico data suggest the importance of monitoring the emergence of new MPXV mutations for the prevention of future outbreaks potentially dangerous for public health. FundingNo funding to declare

bioinformatics↗

bioRxiv2021

Phylogenetic analysis and in silico studies link spike Q675H mutation to SARS-CoV-2 adaptive evolution

Genotype screening was implemented in Italy and showed a significant prevalence of new SARS-CoV-2 mutants carrying Q675H mutation, near the furin cleavage site of spike protein. Currently, this mutation, which is expressed on different SARS-CoV-2 lineages circulating worldwide, has not been thoughtfully investigated. Therefore, we performed phylogenetic and biocomputational analysis to better understand SARS-CoV-2 Q675H mutants evolutionary relationships with other circulating lineages and Q675H function in its molecular context. Our studies reveal that Q675H spike mutation is the result of parallel evolution because it arose independently in separate evolutionary clades. In silico data show that the Q675H mutation gives rise to a hydrogen-bonds network in the spike polar region delimiting the conformational space of the highly flexible loop containing the furin cleavage site. This results in an optimized directionality of arginine residues involved in interaction of spike with the furin binding pocket, thus improving proteolytic exposure of the viral protein. Furin was found to have a greater affinity for Q675H than Q675 substrate conformations. As a consequence, Q675H mutation is likely to confer a fitness advantage to SARS-CoV-2 by promoting a more efficient viral entry. Interestingly, here we show an ongoing increase in the occurrence of Q675H spike mutation in the most common SARS-CoV-2 variants of concern (VOC). This finding highlights that, VOC are still evolving and start acquiring the Q675H mutation. At the same time, it suggests that our hypothesis of fitness advantage prompted by Q675H could be concrete.

bioinformatics↗

bioRxiv2021

Cutting epitopes to survive: the case of lambda variant

This manuscript concisely reports an in-silico study on the potential impact of the Spike protein mutations on immuno-escape ability of SARS-CoV-2 lambda variant. Biophysical and bioinformatics data suggest that a combination of shortening immunogenic epitope loops and generation of potential N-glycosylation sites may be a viable adaptation strategy potentially allowing this emerging viral variant escaping host immunity.

bioinformatics↗

bioRxiv2021

SARS-CoV-2 B.1.617 Indian variants: are electrostatic potential changes responsible for a higher transmission rate?

Lineage B.1.617+, also known as G/452R.V3, is a recently described SARS-CoV-2 variant under investigation (VUI) firstly identified in October 2020 in India. As of May 2021, three sublineages labelled as B.1.617.1, B.1.617.2 and B.1.617.3 have been already identified, and their potential impact on the current pandemic is being studied. This variant has 13 amino acid changes, three in its spike protein, which are currently of particular concern: E484Q, L452R and P681R. Here we report a major effect of the mutations characterizing this lineage, represented by a marked alteration of the surface electrostatic potential (EP) of the Receptor Binding Domain (RBD) of the spike protein. Enhanced RBD-EP is particularly noticeable in the B.1.617.2 sublineage, which shows multiple replacements of neutral or negatively-charged amino acids with positively-charged amino acids. We here hypothesize that this EP change can favor the interaction between the B.1.617+RBD and the negatively-charged ACE2 thus conferring a potential increase in the virus transmission.

bioinformatics↗

bioRxiv2020

The 2019-new Coronavirus epidemic: evidence for virus evolution

There is concern about a new coronavirus, the 2019-nCoV, as a global public health threat. In this article, we provide a preliminary evolutionary and molecular epidemiological analysis of this new virus. A phylogenetic tree has been built using the 15 available whole genome sequence of 2019-nCoV and 12 whole genome sequences highly similar sequences available in gene bank (5 from SARS, 2 from MERS and 5 from Bat SARS-like Coronavirus). FUBAR analysis shows that the Nucleocapsid and the Spike Glycoprotein has some sites under positive pressure while homology modelling helped to explain some molecular and structural differences between the viruses. The phylogenetic tree showed that 2019.nCoV significantly clustered with Bat SARS-like Coronavirus sequence isolated in 2015, whereas structural analysis revealed mutation in S and nucleocapsid proteins. From these results, 2019nCoV could be considered a coronavirus distinct from SARS virus, probably transmitted from bats or another host where mutations conferred upon it the ability to infect humans.

bioinformatics↗