Virome of wild rats (Rattus norvegicus) captured far from pig farms in Jiangsu province of China reveals novel porcine circovirus type 2d (PCV2d) sequences.

BACKGROUND: Porcine circovirus type 2 (PCV2) has caused great economic losses in the global pig industry. There have been published records of wild rats acting as the reservoirs of PCV2 (only PCV2a and PCV2b), but almost all of which were related to the PCV2-infected swine herds. RESULTS: In this study, we carried out the detection, amplification, and characterization of novel PCV2 strains in wild rats that were captured far from pig farms. Nested PCR assay demonstrated that the kidney, heart, lung, liver, pancreas, and large and small intestines of rats were screened positive for PCV2. We subsequently sequenced two full genomes of PCV2 in positive sample pools, designated as js2021-Rt001 and js2021-Rt002. Genome sequence analysis indicated that they had the highest similarity to nucleotide sequences of porcine-origin PCV2 isolates in Vietnam. Phylogenetically, js2021-Rt001 and js2021-Rt002 were a part of the PCV2d genotype cluster, which is a predominant genotype circulating worldwide in recent years. The antibody recognition regions, immunodominant decoy epitope, and heparin sulfate binding motif of the two complete genome sequences coincided with those previously reported. CONCLUSIONS: Our research reported the genomic characterization of two novel PCV2 strains (js2021-Rt001 and js2021-Rt002) and provided the first supported evidence that PCV2d could naturally infect wild rats in China. However, whether the newly identified strains have potential for circulating in nature in vertical and horizontal transmission or inter-species jumping between rats and pigs needs further research.

Dynamic alterations of the mice gut virome after Coxsackievirus B3 infection.

The gut microbiome plays an essential role in the human health and dysbiosis has been implicated in numerous diseases. Coxsackievirus B3 infects millions of humans yearly and yet limited research has explored dynamic alterations of the gut virome after infection. Here, we established the mouse model of Coxsackievirus B3 infection and collected fecal samples at several time points to investigate alterations of the gut virome using viral metagenomic analysis. We found that the mice virome was dominated by Caudovirales and Microviridae, and phylogenetic analyses showed that both Caudovirales and Microviridae had high diversity. The gut virome had significant variations with the increase of Caudovirales and the decrease of Microviridae after infection. We proposed that Caudovirales and Microviridae may be biomarkers for the Coxsackievirus infection process. This study provides a reference for the dynamic changes of the gut virome after human Enterovirus infection, which may help guide the rational drug use in clinical treatment and provide new ideas for preventing Enterovirus infection.

E3 Ubiquitin Ligases: The Operators of the Ubiquitin Code That Regulates the RLR and cGAS-STING Pathways.

The outbreaks caused by RNA and DNA viruses, such as SARS-CoV-2 and monkeypox, pose serious threats to human health. The RLR and cGAS-STING pathways contain major cytoplasmic sensors and signaling transduction axes for host innate antiviral immunity. In physiological and virus-induced pathological states, the activation and inactivation of these signal axes are tightly controlled, especially post-translational modifications (PTMs). E3 ubiquitin ligases (E3s) are the direct manipulator of ubiquitin codons and determine the type and modification type of substrate proteins. Therefore, members of the E3s family are involved in balancing the host's innate antiviral immune responses, and their functions have been extensively studied over recent decades. In this study, we overviewed the mechanisms of different members of three E3s families that mediate the RLR and cGAS-STING axes and analyzed them as potential molecular targets for the prevention and treatment of virus-related diseases.

Viral metagenomics of the gut virome of diarrheal children with Rotavirus A infection.

Diarrhea is a leading cause of morbidity and mortality in children worldwide and represents a major dysbiosis event. Rotavirus has been recognized as a global leading pathogen of diarrhea. This study is aimed at investigating differences in the gut virome between diarrheal children and healthy controls. In 2018, 76 diarrheal fecal samples and 27 healthy fecal samples in Shanghai and 40 diarrheal fecal samples and 19 healthy fecal samples in Taizhou were collected to investigate the composition of the gut virome. Viral metagenomic analyses revealed that the alpha diversity of the diarrheal virome was not significantly different from that of the healthy virome, and the beta diversity had a significant difference between diarrheal and healthy children. The diarrheal virome was mainly dominated by the families Adenoviridae, Astroviridae, Caliciviridae, and Picornaviridae. Meanwhile, the healthy virome also contains phages, including Microviridae and Caudovirales. The high prevalence of diverse enteric viruses in all samples and the little abundance of Microviridae and Caudovirales in diarrheal groups were identified. The study introduced a general overview of the gut virome in diarrheal children, revealed the compositional differences in the gut viral community compared to healthy controls, and provided a reference for efficient treatments and prevention of virus-infectious diarrhea in children.