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Biomedical subjects

Stefano Menzo

Publications and source records attributed to Stefano Menzo.

2 recordsLinked to original sources

Genomic Epidemiology of the Main SARS-CoV-2 Variants Circulating in Italy During the Omicron Era.

Since early 2022 the Omicron variant has rapidly spread worldwide, becoming the dominant variant to date. The study aimed to investigate the clinical and epidemiological characteristics of COVID-19 patients and reconstruct the genomic epidemiology of main SARS-CoV-2 Omicron sublineages in Italy in 2022. A total of 8970 SARS-CoV-2 samples were studied, and phylogenetic analyses were focused on BA.1, BA.2, and BA.5 subvariants. More than half of subjects received three doses of vaccine and experienced a reinfection. A significant larger proportion of unvaccinated subjects presented reinfection compared with vaccinated. Clusters presented a tMRCA between September-November 2021 (BA.1), November 2021-January 2022 (BA.2), and October 2021-May 2022 (BA.5). Re values showed the highest level between September-October, January-February 2022, and May 2022 for BA.1, BA.2 and BA.5, respectively. Limited number of studied variant sequences are included in clusters. The spread rate of the studied variant exceeded its evolutionary rate. No single sublineage had sufficient time to differentiate into large clusters, but only into small and fragmented groups sharing the same recent ancestor. These analyses dissect the epidemiological dynamics of Omicron sublineages in Italy over a period of great epidemiological changes in the COVID-19 epidemic.

Humans

Adeno-Associated Virus Type 5 Infection via PDGFRα Is Associated With Interstitial Lung Disease in Systemic Sclerosis and Generates Composite Peptides and Epitopes Recognized by the Agonistic Immunoglobulins Present in Patients With Systemic Sclerosis.

OBJECTIVE: The etiopathogenesis of systemic sclerosis (SSc) is unknown. Platelet-derived growth factor receptors (PDGFRs) are overexpressed in patients with SSc. Because PDGFR&#x3b1; is targeted by the adeno-associated virus type 5 (AAV5), we investigated whether AAV5 forms a complex with PDGFR&#x3b1; exposing epitopes that may induce the immune responses to the virus-PDGFR&#x3b1; complex. METHODS: The binding of monomeric human PDGFR&#x3b1; to the AAV5 capsid was analyzed by in silico molecular docking, surface plasmon resonance (SPR), and genome editing of the PDGFR&#x3b1; locus. AAV5 was detected in SSc lungs by in situ hybridization, immunohistochemistry, confocal microscopy, and molecular analysis of bronchoalveolar lavage (BAL) fluid. Immune responses to AAV5 and PDGFR&#x3b1; were evaluated by SPR using SSc monoclonal anti-PDGFR&#x3b1; antibodies and immunoaffinity-purified anti-PDGFR&#x3b1; antibodies from sera of patients with SSc. RESULTS: AAV5 was detected in the BAL fluid of 41 of 66 patients with SSc with interstitial lung disease (62.1%) and in 17 of 66 controls (25.75%) (P <&#x2009;0.001). In SSc lungs, AAV5 localized&#x2009;in type II pneumocytes and in interstitial cells. A molecular complex formed of spatially contiguous epitopes of the AAV5 capsid and of PDGFR&#x3b1; was identified and characterized. In silico molecular docking analysis and binding to the agonistic anti-PDGFR&#x3b1; antibodies identified spatially contiguous epitopes derived from PDGFR&#x3b1; and AAV5 that interacted with SSc agonistic antibodies to PDGFR&#x3b1;. These peptides were also able to bind total IgG isolated from patients with SSc, not from healthy controls. CONCLUSION: These data link AVV5 with the immune reactivity to endogenous antigens in SSc and provide a novel element in the pathogenesis of SSc.

Humans