The 2015-2016 outbreak of Zika virus (ZIKV) disease has affected many countries and is a major public health concern. ZIKV is associated with fetal microcephaly and neurological complications, and countermeasures are needed to treat and prevent ZIKV infection. We report the isolation of 13 specific human monoclonal antibodies from a single patient infected with ZIKV. Two of the isolated antibodies (Z23 and Z3L1) demonstrated potent ZIKV-specific neutralization in vitro without binding or neutralizing activity against strains 1 to 4 of dengue virus, the closest relative to ZIKV. These two antibodies provided postexposure protection to mice in vivo. Structural studies revealed that Z23 and Z3L1 bound to tertiary epitopes in envelope protein domain I, II, or III, indicating potential targets for ZIKV-specific therapy. Our results suggest the potential of antibody-based therapeutics and provide a structure-based rationale for the design of future ZIKV-specific vaccines.

Rickettsiales are important zoonotic pathogens, causing severe disease in humans globally. Although mosquitoes are an important vector for diverse pathogens, with the exception of members of the genus Wolbachia little is known about their role in the transmission of Rickettsiales. Herein, Rickettsiales were identified by PCR in five species of mosquitoes (Anopheles sinensis, Armigeres subalbatus, Aedes albopictus, Culex quinquefasciatus and Cu. tritaeniorhynchus) collected from three Chinese provinces during 2014–2015. Subsequent phylogenetic analyses of the rrs, groEL and gltA genes revealed the presence of Anaplasma, Ehrlichia, Candidatus Neoehrlichia, and Rickettsia bacteria in mosquitoes, comprising nine documented and five tentative species bacteria, as well as three symbionts/endosybionts. In addition, bacteria were identified in mosquito eggs, larvae, and pupae sampled from aquatic environments. Hence, these data suggest that Rickettsiales circulate widely in mosquitoes in nature. Also of note was that Ehrlichia and Rickettsia bacteria were detected in each life stage of laboratory cultured mosquitoes, suggesting that Rickettsiales may be maintained in mosquitoes through both transstadial and transovarial transmission. In sum, these data indicate that mosquitoes may have played an important role in the transmission and evolution of Rickettsiales in nature.

Although shrews are one of the largest groups of mammals little is known about their role in the evolution and transmission of viral pathogens including coronaviruses. We captured 266 Asian house shrews () in Jiangxi and Zhejiang provinces, China, during 2013-2015. Coronavirus (CoV) RNA was detected in 24 Asian house shrews, with an overall prevalence of 9.02%. Complete viral genome sequences were successfully recovered from the RNA positive samples. The newly discovered shrew CoV fell into four lineages reflecting their geographic origins, indicative of largely allopatric evolution. Notably, these viruses were most closely related to alphacoronaviruses, but sufficiently divergent that they should be considered a novel member of the genus , which we denote Wénchéng shrew virus (WESV). Phylogenetic analysis revealed that WESV was a highly divergent member of the alphacoronaviruses and, more dramatically, that the S gene of WESV fell in a cluster that was genetically distinct from that of known coronaviruses. The divergent position of WESV suggests that coronaviruses have a long association with Asian house shrews. In addition, the genome of WESV contains a distinct NS7 gene that exhibits no sequence similarity to any known viruses. Together, these data suggest that shrews are natural reservoirs for coronaviruses and may have played an important and long-term role in CoV evolution. The subfamily contains several notorious human and animal pathogens, including severe acute respiratory syndrome coronavirus, Middle East respiratory syndrome coronavirus, and porcine epidemic diarrhea virus. Because of their genetic diversity and phylogenetic relationships it has been proposed that the alphacoronaviruses likely have their ultimate ancestry in those viruses residing in bats. Here, we described a novel alphacoronavirus (Wénchéng shrew virus, WESV) that was sampled from Asian house shrews in China. Notably, WESV is a highly divergent member of the alphacoronaviruses and possesses an S gene that is genetically distinct from that of all known coronaviruses. In addition, the genome of WESV contains a distinct NS7 gene that exhibits no sequence similarity to any known viruses. Together, these data suggest that shrews are important and long-standing hosts for coronaviruses that merit additional research and surveillance.

Diseases caused by Rickettsiales bacteria are a global public health problem. To better understand the diversity and origins of Rickettsiales infection in humans and animals, we sampled 134 febrile patients, 173 rodents and 43 shrews, as well as 358 ticks, from two cities in Jiangsu and Jiangxi provinces, China. Our data revealed a relatively high prevalence of scrub typhus cases in both localities. In addition, both serological tests and genetic analysis identified three patients infected with Anaplasma bovis, Rickettsia monacensis, and Orientia tsutsugamushi bacteria. Molecular epidemiological investigation revealed the co-circulation of multiple species of Rickettsiales bacteria in small mammals and ticks in both provinces, potentially including novel bacterial species. In sum, these data demonstrate the ongoing importance of Rickettsiales infection in China and highlight the need for the regular surveillance of local arthropods, mammals and humans.

Live poultry markets (LPMs) are an important source of novel avian influenza viruses (AIV). During 2015-2016 we surveyed AIV diversity in ten LPMs in Hubei, Zhejiang and Jiangxi provinces, China. A high diversity and prevalence of AIVs (totaling 12 subtypes) was observed in LPMs in these provinces. Strikingly, however, the subtypes discovered during 2015-2016 were markedly different to those reported by us in these same localities one year previously, suggesting a dynamic shift in viral genetic diversity over the course of a single year. Phylogenetic analyses revealed frequent reassortment, including between high and low pathogenic AIV subtypes and among those that circulate in domestic and wild birds. Notably, the novel H5N6 reassortant virus, which contains a set of H9N2-like internal genes, was prevalent in all three regions surveyed. Overall, these data highlight the profound changes in genetic diversity and in patterns of reassortment in those AIVs that circulate in LPMs.

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Chinese horseshoe crabs ( Tachypleus tridentatus ), ancient marine arthropods dating back to the mid-Palaeozoic Era, have provided valuable resources for the detection of bacterial or fungal contamination. However, excessive exploitation for the amoebocyte lysate of Tachypleus has dramatically decreased the population of the Chinese horseshoe crabs. Thus, we present sequencing, assembly and annotation of T. tridentatus, with the hope of understanding the genomic feature of the living fossil and assisting scientists with the protection of this endangered species. The final genome contained a total size of 1.943 Gb, covering 90.23% of the estimated genome size. The transcriptome of three larval stages was constructed to investigate the candidate gene involved in the larval development and validate annotation. The completeness of the genome and gene models was estimated by BUSCO, reaching 96.2% and 95.4%, respectively. The synonymous substitution distribution of paralogues revealed that T. tridentatus had undergone two rounds of whole-genome duplication. All genomic and transcriptome data have been deposited in public databases, ready to be used by researchers working on horseshoe crabs.

Patients with laryngeal cancer with early relapse usually have a poor prognosis. In this study, we aimed to identify a multi‐gene signature to improve the relapse prediction in laryngeal cancer. One microarray data set GSE27020 (training set, N = 109) and one RNA‐sequencing data set (validation set, N = 85) were included into the analysis. In the training set, the microarray expression profile was re‐annotated into an mRNA‐long noncoding RNA (lncRNA) biphasic profile. Then, LASSO Cox regression model identified nine relapse‐related RNA (eight mRNA and one lncRNA), and a risk score was calculated for each sample according to the model coefficients. Patients with high‐risk showed poorer relapse‐free survival than patients with low risk (hazard ratios (HR): 6.189, 95% confidence interval (CI): 3.075‐12.460, P < 0.0001). The risk score demonstrated good accuracy in predicting the relapse (area under time‐dependent receiver‐operating characteristic (AUC): 0.859 at 1 year, 0.822 at 3 years, and 0.815 at 5 years). The results were validated in the validation set (HR: 3.762, 95% CI: 1.594‐8.877, P = 0.011; AUC: 0.770 at 1 year, 0.769 at 3 years, and 0.728 at 5 years). The multivariate analysis reached consistent results after adjustment by multiple confounders. When compared with a 27‐gene signature, a 2‐lncRNA signature, and Tumor‐Node‐Metastasis stage, the risk score also showed better performance (P < 0.05). In conclusion, we successfully developed a robust mRNA‐lncRNA signature that can accurately predict the relapse in laryngeal cancer.