ABSTRACT
Patients with pre-existing medical conditions are at a heightened risk of contracting severe acute respiratory syndrome (SARS), SARS-CoV-2, and influenza viruses, which can result in more severe disease progression and increased mortality rates. Nevertheless, the molecular mechanism behind this phenomenon remained largely unidentified. Here, we found that microRNA-19a/b (miR-19a/b), which is a constituent of the miR-17-92 cluster, exhibits reduced expression levels in patients with coronary heart disease in comparison to healthy individuals. The downregulation of miR-19a/b has been observed to facilitate the replication of influenza A virus (IAV). miR-19a/b can effectively inhibit IAV replication by targeting and reducing the expression of SOCS1, as observed in cell-based and coronary heart disease mouse models. This mechanism leads to the alleviation of the inhibitory effect of SOCS1 on the interferon (IFN)/JAK/STAT signaling pathway. The results indicate that the IAV employs a unique approach to inhibit the host's type I IFN-mediated antiviral immune responses by decreasing miR-19a/b. These findings provide additional insights into the underlying mechanisms of susceptibility to flu in patients with coronary heart disease. miR-19a/b can be considered as a preventative/therapy strategy for patients with coronary heart disease against influenza virus infection.
ABSTRACT
We analyzed the clinical characteristics of outpatients with influenza-B-associated pneumonia during the 2021-2022 influenza season and analyzed the molecular epidemiology and evolution of influenza B virus. The presence of influenza B virus was confirmed by reverse transcription polymerase chain reaction (RT-PCR). Electronic medical records were used to collect and analyze data of outpatients. The HA and NA genes were phylogenetically analyzed using ClustalW 2.10 and MEGA 11.0. Out of 1569 outpatients who tested positive for influenza B virus, 11.7% (184/1569) developed pneumonia, and of these, 19.0% (35/184) had underlying diseases. Fever, cough, and sore throat were the most common symptoms. Among the complications, acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), and shock accounted for 2.7% (5/184), 4.9% (9/184), and 1.6% (3/184), respectively. Of the outpatients, 2.7% (5/184) were admitted to the hospital, and 0.5% (1/184) of them died. All of the strains from Beijing were identified as belonging to the B/Victoria lineage. The HA and NA gene sequences of 41 influenza B viruses showed high similarity to each other, and all of them belonged to clade 1A.3. Compared with the vaccine strain B/Washington/02/2019, all of the isolates contained N150K, G181E, and S194D mutations. S194D, E195K, and K200R mutations were detected in the 190 helix of the receptor binding region of HA. Co-mutations of H122Q, A127T, P144L, N150K, G181E, S194D, and K200R in HA and D53N, N59S, and G233E in NA were detected in 78.0% (32/41) of the isolates, and 56.3% (18/32) of these were from outpatients with influenza-B-associated pneumonia. Influenza outpatients with underlying diseases were more likely to develop pneumonia. No significant differences were observed in clinical symptoms or laboratory results between outpatients with and without pneumonia, so testing for influenza virus seems to be a good choice. The observed amino acid variations suggest that current vaccines might not provide effective protection.