Hepatitis C virus (HCV; genus Hepacivirus) represents a major public health problem, infecting about 3% of the human population. Because no animal reservoir carrying closely related hepaciviruses has been identified, the zoonotic origins of HCV still remain unresolved. Motivated by recent findings of divergent hepaciviruses in rodents and a plausible African origin of HCV genotypes, we have screened a large collection of small mammals samples from seven sub-Saharan African countries. Out of 4,303 samples screened, 80 were found positive for the presence of hepaciviruses in 29 different host species. We here report 56 novel genomes that considerably increase the diversity of three divergent rodent hepacivirus lineages. Furthermore, we provide strong evidence for hepacivirus co-infections in rodents, which were exclusively found in four sampled species of brush-furred mice. We also detect evidence of recombination within specific host lineages. Our study expands the available hepacivirus genomic data and contributes insights into the relatively deep evolutionary history of these pathogens in rodents. Overall, our results emphasise the importance of rodents as a potential hepacivirus reservoir and as models for investigating HCV infection dynamics.

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Abstract. Tripterygium glycoside (TG), an active ingredient of the widely used chinese herb Tripterygium wilfordii Hook F, has immunosuppressive and anti-inflammatory effects. Previous studies have indicated that TG is a potentially effective therapeutic option to treat nephrotic syndrome. The mechanism underlying the therapeutic effect of TG, including its effect on autophagy and apoptosis in podocyte injury, remains to be fully elucidated. The present study aimed to assess the protective effect of TG on podocytes via its potential role in the activation of autophagic and phosphatidylinositol 3-kinase (PI3K) pathways. Using flow cytometry, western blot analysis, cell counting kit-8 assays and transmission electron microscopy analysis, the effects of TG on puromycin aminonucleoside (PAN)-induced podocyte injury were investigated. chloroquine (cQ), an inhibitor of autophagy, was used to assess the importance of autophagy in the protective effect of TG. In addition, LY294002, an inhibitor of class III PI3K, was used to identify which signaling pathways TG is involved in. PAN caused marked apoptosis of podocytes, which was significantly antagonized by TG. The expression of microtubule-associated protein 1A/1B-light chain 3 and the appearance of autophagosomes increased significantly following TG treatment, whereas the expression levels of p62 and cleaved caspase-3 were markedly decreased. Podocyte apoptosis decreased significantly when the podocytes were treated with TG compared with the levels of apoptosis in the PAN-and PAN+cQ-treated groups. The expression of phosphorylated AKT was increased significantly in the TG-treated groups, and the effects of TG on the podocytes were significantly inhibited by LY294002. In conclusion, TG protected podocytes from PAN-induced injury, and the effects were attributable to the activation of autophagy, mainly via a PI3K-dependent pathway.