The compound 1,2,3,4,6-penta-O-galloyl-β-d-glucose (PGG), a gallotannin present in various plants such as Rhus chinensis Mill and Paeonia suffruticosa, has a broad spectrum of antiviral effects. The present study investigated its potency against infection of mice with rabies virus (RABV). Results demonstrated that PGG strongly inhibited virus titers (50-fold), viral mRNA expression (up to 90%), and protein synthesis in vitro. Importantly, we found that PGG not only suppressed viral adsorption and entry, but also directly inactivated RABV through suppression of autophagy by mediating activation of the mTOR-dependent autophagy signaling pathway. In vivo, PGG (10 mg/kg) alleviated the clinical symptoms and reduced the mortality of infected mice by 27.3%. Collectively, our results indicate that PGG has potent anti-RABV effect, and merits further investigation as an anti-RABV drug.

In 2015, China and other member states of the United Nations adopted the goal of eliminating dog-mediated rabies by 2030. China has made substantial progress in reducing dog-mediated human rabies since peaking with more than 3,300 reported cases in 2007. To further improve coordination and planning, the Chinese Center for Disease Control and Prevention, in collaboration with the United States Centers for Disease Control and Prevention, conducted a Stepwise Approach towards Rabies Elimination (SARE) assessment in March 2019. Assessment goals included outlining progress and identifying activities critical for eliminating dog-mediated rabies. Participants representing national, provincial and local human and animal health sectors in China used the SARE assessment tool to answer 115 questions about the current dog-mediated rabies control and prevention programs in China. The established surveillance system for human rabies cases and availability of post-exposure prophylaxis were identified as strengths. Low dog vaccination coverage and limited laboratory confirmation of rabid dogs were identified gaps, resulting in an overall score of 1.5 on a scale of 0 to 5. Participants outlined steps to increase cross-sectoral information sharing, improve surveillance for dog rabies, increase dog vaccination coverage, and increase laboratory capacity to diagnose rabies at the provincial level. All assessment participants committed to strengthening cross-sector collaboration using a One Health approach to achieve dog-mediated human rabies elimination by 2030.

Avian H3N2 influenza virus follows cross-host transmission and has spread among dogs in Asia since 2005. After 2015–2016, a new H3N2 subtype canine influenza epidemic occurred in dogs in North America and Asia. The disease prevalence was assessed by virological and serological surveillance in dogs in China. Herein, five H3N2 canine influenza virus (CIV) strains were isolated from 1185 Chinese canine respiratory disease samples in 2017–2018; these strains were on the evolutionary branch of the North American CIVs after 2016 and genetically far from the classical canine H3N2 strain discovered in China before 2016. Serological surveillance showed an HI antibody positive rate of 6.68%. H3N2 was prevalent in the coastal areas and northeastern regions of China. In 2018, it became the primary epidemic strain in the country. The QK01 strain of H3N2 showed high efficiency in transmission among dogs through respiratory droplets. Nevertheless, the virus only replicated in the upper respiratory tract and exhibited low pathogenicity in mice. Furthermore, highly efficient transmission by direct contact other than respiratory droplet transmission was found in a guinea pig model. The low-level replication in avian species other than ducks could not facilitate contact and airborne transmission in chickens. The current results indicated that a novel H3N2 virus has become a predominant epidemic strain in dogs in China since 2016 and acquired highly efficient transmissibility but could not be replicated in avian species. Thus, further monitoring is required for designing optimal immunoprophylactic tools for dogs and estimating the zoonotic risk of CIV in China.

Swine coronaviruses (CoVs) have been found to cause infection in humans, suggesting that Suiformes might be potential intermediate hosts in CoV transmission from their natural hosts to humans. The present study aims to establish convolutional neural network (CNN) models to predict host adaptation of swine CoVs. Decomposing of each ORF1ab and Spike sequence was performed with dinucleotide composition representation (DCR) and other traits. The relationship between CoVs from different adaptive hosts was analyzed by unsupervised learning, and CNN models based on DCR of ORF1ab and Spike were built to predict the host adaptation of swine CoVs. The rationality of the models was verified with phylogenetic analysis. Unsupervised learning showed that there is a multiple host adaptation of different swine CoVs. According to the adaptation prediction of CNN models, swine acute diarrhea syndrome CoV (SADS-CoV) and porcine epidemic diarrhea virus (PEDV) are adapted to Chiroptera, swine transmissible gastroenteritis virus (TGEV) is adapted to Carnivora, porcine hemagglutinating encephalomyelitis (PHEV) might be adapted to Primate, Rodent, and Lagomorpha, and porcine deltacoronavirus (PDCoV) might be adapted to Chiroptera, Artiodactyla, and Carnivora. In summary, the DCR trait has been confirmed to be representative for the CoV genome, and the DCR-based deep learning model works well to assess the adaptation of swine CoVs to other mammals. Suiformes might be intermediate hosts for human CoVs and other mammalian CoVs. The present study provides a novel approach to assess the risk of adaptation and transmission to humans and other mammals of swine CoVs.

Influenza A virus (IAV) is a leading cause of human respiratory infections and poses a major public health concern. IAV replication can affect the expression of DNA methyltransferases (DNMTs), and the subsequent changes in DNA methylation regulate gene expression and may lead to abnormal gene transcription and translation, yet the underlying mechanisms of virus-induced epigenetic changes from DNA methylation and its role in virus–host interactions remain elusive. Here in this paper, we showed that DNMT1 expression could be suppressed following the inhibition of miR-142-5p or the PI3K/AKT signaling pathway during IAV infection, resulting in demethylation of the promotor region of the 2′-5′-oligoadenylate synthetase-like (OASL) protein and promotion of its expression in A549 cells. OASL expression enhanced RIG-I-mediated interferon induction and then suppressed replication of IAV. Our study elucidated an innate immunity mechanism by which up-regulation of OASL contributes to host antiviral responses via epigenetic modifications in IAV infection, which could provide important insights into the understanding of viral pathogenesis and host antiviral defense.

South-East Asia (SEA) and South Asia (SA) are two important geographic regions with the most severe enzootic rabies in the world. In these regions, phylogenetic analysis of rabies virus (RABV) has been conducted only at a country level; the results obtained from different countries are scattered and unequal, with a non-uniform system to name RABV genotypes. Therefore, it is difficult to undertake origin-tracking and compare inter-country RABV evolution and transmission. To avoid the confusion in understanding and to generate a panoramic picture of RABV genetic diversity, distribution, and transmission in SEA and SA, the present study conducted a systematic phylogenetic analysis by combining all sequences representing 2368 RABV strains submitted to GenBank by 14 rabies endemic SEA and SA countries. The results showed that RABVs circulating in two regions were classified into four major clades and many subclades: the Asia clade is circulating only in SEA, the Indian subcontinent, and Arctic-like clades only in SA, while the Cosmopolitan clade has been detected in both regions. The results also showed a wide range of hosts were infected by divergent RABV subclades, with dogs being the major transmission source. However, wildlife rabies was also found to be an important issue with 6 wild carnivore species identified as potential sources of spillover risk for sylvatic rabies to humans, domestic animals, and other wild animals. Current findings indicate that the two regions have separate virus clades circulating thus indicating the absence of cross-transmission between the regions. The study emphasizes the importance of phylogenetic analysis in the regions using uniform genotyping and naming systems for rabies surveillance, to coordinate actions of member countries to eliminate dog-mediated human rabies by 2030.