A Statovirus-like virus from respiratory tracts of patients, China.

The emerging evidence of human infections with emerging viruses suggests their potential public health importance. A novel taxon of viruses named Statoviruses (for stool-associated Tombus-like viruses) was recently identified in the gastrointestinal tracts of multiple mammals. Here we report the discovery of respiratory Statovirus-like viruses (provisionally named Restviruses) from the respiratory tracts of five patients experiencing acute respiratory disease with Human coronavirus OC43 infection through the retrospective analysis of meta-transcriptomic data. Restviruses shared 53.1%-98.8% identities of genomic sequences with each other and 39.9%-44.3% identities with Statoviruses. The phylogenetic analysis revealed that Restviruses together with a Stato-like virus from nasal-throat swabs of Vietnamese patients with acute respiratory disease, formed a well-supported clade distinct from the taxon of Statoviruses. However, the consistent genome characteristics of Restviruses and Statoviruses suggested that they might share similar evolutionary trajectories. These findings warrant further studies to elucidate the etiological and epidemiological significance of the emerging Restviruses.

Continuous evolution and emerging lineage of seasonal human coronaviruses: A multicenter surveillance study.

The seasonal human coronaviruses (HCoVs) have zoonotic origins, repeated infections, and global transmission. The objectives of this study are to elaborate the epidemiological and evolutionary characteristics of HCoVs from patients with acute respiratory illness. We conducted a multicenter surveillance at 36 sentinel hospitals of Beijing Metropolis, China, during 2016-2019. Patients with influenza-like illness (ILI) and severe acute respiratory infection (SARI) were included, and submitted respiratory samples for screening HCoVs by multiplex real-time reverse transcription-polymerase chain reaction assays. All the positive samples were used for metatranscriptomic sequencing to get whole genomes of HCoVs for genetical and evolutionary analyses. Totally, 321 of 15 677 patients with ILI or SARI were found to be positive for HCoVs, with an infection rate of 2.0% (95% confidence interval, 1.8%-2.3%). HCoV-229E, HCoV-NL63, HCoV-OC43, and HCoV-HKU1 infections accounted for 18.7%, 38.3%, 40.5%, and 2.5%, respectively. In comparison to ILI cases, SARI cases were significantly older, more likely caused by HCoV-229E and HCoV-OC43, and more often co-infected with other respiratory pathogens. A total of 179 full genome sequences of HCoVs were obtained from 321 positive patients. The phylogenetical analyses revealed that HCoV-229E, HCoV-NL63 and HCoV-OC43 continuously yielded novel lineages, respectively. The nonsynonymous to synonymous ratio of all key genes in each HCoV was less than one, indicating that all four HCoVs were under negative selection pressure. Multiple substitution modes were observed in spike glycoprotein among the four HCoVs. Our findings highlight the importance of enhancing surveillance on HCoVs, and imply that more variants might occur in the future.

The suppression of innate immune response by human rhinovirus C.

Rhinovirus C (RV-C), a newly identified group of human rhinoviruses (RVs), is associated with exacerbation of severe asthma. The type I interferon (IFN) response induced by this virus and the mechanisms of evasion of IFN-mediated innate immunity for RV-C remain unclear. In this study, we constructed a full-length cDNA clone of RV-C (LZ651) from a clinical sample. IFN-ß mRNA and protein levels were not elevated in differentiated Human bronchial epithelial (HBE) cells at the air-liquid interface infected with RV-C, except in the early stage of infection. The ability to attenuate IFN-ß activation was ascribed to 3Cpro of RV-C, and the 40-His site of 3Cpro played an important role. Furthermore, RIG-I was degraded by 3Cpro in a caspase-dependent manner and 3Cpro cleaved MAVS at 148 Q/A, which inhibited IFN signaling. Taken together, our results demonstrate the mechanism by which RV-C circumvents the production of type I IFN in infected cells.

Identification and genetic characterization of two porcine astroviruses from domestic piglets in China.

Porcine astrovirus are divided into five genotypes. In this study, we identified two porcine astroviruses (AstV-LL-1 and AstV-LL-2) by using sequence-independent single-primer amplification (SISPA) on faecal specimens of healthy domestic piglets younger than 15 days. The detection rate for both was 2.82% (14/497). AstV-LLs were then sequenced and characterised. Phylogenetic analysis revealed that they have the characteristics of porcine astrovirus (PastV) 2 and 5 and have some unique genetic features. Our findings show that the two astroviruses are novel lineages of PAstV2 and 5. The findings may be helpful in evaluating the ecology and evolution of astroviruses in pigs.

Development and influencing factors of compliance behaviors of investigators in clinical trials.

The development and influencing factors of compliance behavior of investigators in clinical trials were explored. According to literature review, a hypothetical model of development of compliance behavior of investigators in clinical trials was established, and the influencing factors of compliance behavior of investigators and their interrelationships were studied based on questionnaire survey of five hundred investigators sampled randomly from one hundred clinical trial institutions in China. Cronbach's alpha coefficient and structural equation modeling were adopted to empirically analyze the results. Six variables in the hypothetical model were included: compliance behavior of investigators, credibility of clinical trial, capability of government regulation, quality control of sponsor, quality control of clinical institution and compliance intention of investigators. Empirical analysis showed that the compliance behavior of investigators in clinical trial was directly affected by compliance intention of investigators, quality control of sponsor and quality control of clinical institution. In addition, credibility of clinical trial and capability of government regulation indirectly affected the compliance behavior of investigators in clinical trial through influencing the compliance intention of investigators, quality control of sponsor and quality control of clinical institution. Quality control of sponsor was affected by credibility of clinical trial and capability of government regulation while quality control of clinical institution was only influenced by capability of government regulation.

Association of Chemotactic Chemokine Ligand 5 Polymorphisms with the Risk of Developing Severe Enterovirus 71 Infection.

Respiratory damage is a main manifestation of severe Enterovirus 71 (EV71) infection. Polymorphisms of -403G/A (rs2107538), -28C/G (rs2280788), and In1.1T/C (rs2280789) in chemotactic chemokine ligand 5 (CCL5) have linked with many respiratory diseases. In this study, we explored the possible correlation of CCL5 polymorphisms with severe EV71 infection. Blood samples were obtained from 87 children hospitalized for EV71 infection. Fifty-seven healthy children were enrolled as asymptomatic controls. Genotype and allele frequencies were analyzed by logistic regression analysis. There were statistically significant differences in polymorphisms of CCL5 -403G/A and In1.1T/C for dominant model (P = 0.016; P = 0.027) and additive model (P = 0.010; P = 0.019) between patients with severe EV71 infection and asymptomatic controls. With ordinal logistic regression model analysis, statistically significant differences were found between polymorphisms of CCL5 (-403G/A) (P = 0.034) with the severity of EV71 infection after adjusting for age. The frequency of A-C-C haplotype was significantly higher in EV71 infection patients than controls (P = 0.032). These results suggest that CCL5 -403G/A and In1.1T/C polymorphisms may contribute to severe EV71 infection and individuals with haplotype of A-C-C may exhibit higher risk of developing severe EV71 infection. These findings may provide insights into pathogenic and protective mechanisms of severe EV71 infection.