Identification and Genomic Characterization of Two Novel Hepatoviruses in Shrews from Yunnan Province, China.

Hepatitis A virus (HAV), a member of the genus Hepatovirus (Picornaviridae HepV), remains a significant viral pathogen, frequently causing enterically transmitted hepatitis worldwide. In this study, we conducted an epidemiological survey of HepVs carried by small terrestrial mammals in the wild in Yunnan Province, China. Utilizing HepV-specific broad-spectrum RT-PCR, next-generation sequencing (NGS), and QNome nanopore sequencing (QNS) techniques, we identified and characterized two novel HepVs provisionally named EpMa-HAV and EpLe-HAV, discovered in the long-tailed mountain shrew (Episoriculus macrurus) and long-tailed brown-toothed shrew (Episoriculus leucops), respectively. Our sequence and phylogenetic analyses of EpMa-HAV and EpLe-HAV indicated that they belong to the species Hepatovirus I (HepV-I) clade II, also known as the Chinese shrew HepV clade. Notably, the codon usage bias pattern of novel shrew HepVs is consistent with that of previously identified Chinese shrew HepV. Furthermore, our structural analysis demonstrated that shrew HepVs differ from other mammalian HepVs in RNA secondary structure and exhibit variances in key protein sites. Overall, the discovery of two novel HepVs in shrews expands the host range of HepV and underscores the existence of genetically diverse animal homologs of human HAV within the genus HepV.

PPAR gamma protects cardiomyocytes against oxidative stress and apoptosis via Bcl-2 upregulation.

Cardiovascular disease (CVD) is a leading cause of death and disabilities worldwide. Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists possess potent anti-inflammatory actions and have recently emerged as potential therapeutic agents for CVD. Here we show that H2O2 induced apoptosis in cardiomyocytes with a marked down-regulation of Bcl-2 protein. The PPARgamma agonist rosiglitazone protected cardiomyocytes from oxidative stress and apoptosis. Cardiomyocytes constitutively overexpressing PPARgamma were resistant to oxidative stress-induced apoptosis and protected against impairment of mitochondrial function. On the contrary, cells expressing a dominant negative mutant of PPARgamma were highly sensitive to oxidative stress. Cells overexpressing PPARgamma exhibited an almost 3 fold increase in Bcl-2 protein content; whereas, in PPARgamma dominant negative expressing cells, Bcl-2 was barely detected. Bcl-2 knockdown by siRNA in cells overexpressing PPARgamma results in increased sensitivity to oxidative stress, suggesting that Bcl-2 up-regulation mediated the protective effects of PPARgamma. These data suggest that, in oxidative stress-induced cardiomyocyte apoptosis, PPARgamma protects cells from oxidative stress through upregulating Bcl-2 expression. These findings provide further support for the use of PPARgamma agonists in ischemic cardiac disease.