[Mammalian DMRTs: Structure, function and relationship with cancer].

DMRT, a gene family related to sexual determination, encodes a large group of transcription factors (DMRTs) with the double-sex and mab-3 (DM) domain (except for DMRT8), which is able to bind to and regulate DNAs. Current studies have shown that the DMRT gene family plays a critical role in the development of sexual organs (such as gender differentiation, gonadal development, germ cell development, etc.) as well as extrasexual organs (such as musculocartilage development, nervous system development, etc.). Additionally, it has been suggested that DMRTs may be involved in the cancer development and progression (such as prostate cancer, breast cancer, lung cancer, etc.). This review summarizes the research progress about the mammalian DMRTs' structure, function and its critical role in cancer development, progression and therapy (mainly in human and mice), which suggests that DMRT gene could be a candidate gene in the study of tumor formation and therapeutic strategy.

Detection and genome characterization of two novel papillomaviruses and a novel polyomavirus in tree shrew (Tupaia belangeri chinensis) in China.

BACKGROUND: Papillomaviruses (PVs) and polyomaviruses (PyVs) infect diverse vertebrates including human and cause a broad spectrum of outcomes from asymptomatic infection to severe disease. There has been no PV and only one PyV detected in tree shrews, though the genomic properties of tree shrews are highly similar to those of the primates. METHODS: Swab and organ samples of tree shrews collected in the Yunnan Province of China, were tested by viral metagenomic analysis and random PCR to detect the presence of PVs and PyVs. By PCR amplification using specific primers, cloning, sequencing and assembling, genomes of two PVs and one PyV were identified in the samples. RESULTS: Two novel PVs and a novel PyV, named tree shrew papillomavirus 1 and 2 (TbelPV1 and TbelPV2) and polyomavirus 1 (TbelPyV1) were characterized in the Chinese tree shrew (Tupaia belangeri chinensis). The genomes of TbelPV1, TbelPV2, and TbelPyV1 are 7410 bp, 7526 bp, and 4982 bp in size, respectively. The TbelPV1 genome contains 7 putative open-reading frames (ORFs) coding for viral proteins E1, E2, E4, E6, E7, L1, and L2; the TbelPV2 genome contains 6 ORFs coding for viral proteins E1, E2, E6, E7, L1, and L2; and the TbelPyV1 genome codes for the typical small and large T antigens of PyV, as well as the VP1, VP2, and VP3 capsid proteins. Genomic comparison and phylogenetic analysis indicated that TbelPV1 and TbelPV2 represented 2 novel PV genera of Papillomaviridae, and TbelPyV1 represented a new species of genus Alphapolyomavirus. Our epidemiologic study indicated that TbelPV1 and TbelPV2 were both detected in oral swabs, while TbelPyV1 was detected in oral swabs and spleens. CONCLUSION: Two novel PVs (TbelPV1 and TbelPV2) and a novel PyV (TbelPyV) were discovered in tree shrews and their genomes were characterized. TbelPV1, TbelPV2, and TbelPyV1 have the highest similarity to Human papillomavirus type 63, Ursus maritimus papillomavirus 1, and Human polyomavirus 9, respectively. TbelPV1 and TbelPV2 only showed oral tropism, while TbelPyV1 showed oral and spleen tropism.

Systematic review of comparing single-incision versus conventional laparoscopic right hemicolectomy for right colon cancer.

BACKGROUND: Single-incision laparoscopic right hemicolectomy (SILS) has long used in surgery for a long time. However, there is barely a systemic review related to the comparison between the SILS and the conventional laparoscopic right hemicolectomy (CLS) for the right colon cancer in the long term follow-up. Herein, we used the most recent articles to compare these two techniques by meta-analysis. METHODS: We searched PubMed, Web of Science, Cochrane Library and Wanfang databases to compare SILS with CLS for right colon cancer up to May 2019. The operative, postoperative, pathological and mid-term follow-up outcomes of nine studies were extracted and compared. RESULTS: A total of 1356 patients participated in 9 studies, while 653 patients were assigned to the SILS group and 703 patients were assigned to the CLS group. The patients' baselines in the SILS group were consistent with those in the CLS group. Compared to the CLS group, the SILS group had a shorter operation duration (SMD - 23.49, 95%CI - 36.71 to - 10.27, P < 0.001, chi-square = 24.11), shorter hospital stay (SMD - 0.76, 95% `CI - 1.07 to - 0.45, P < 0.001, chi-square = 9.85), less blood loss (SMD - 8.46, 95% CI - 14.59 to - 2.34; P < 0.05; chi-square = 2.26), smaller incision length (SMD - 1.60, 95% CI - 2.66 to - 0.55, P < 0.001; chi-square = 280.44), more lymph node harvested (SMD - 0.98, 95% CI - 1.79 to - 0.16, P < 0.05; chi-square = 4.61), and a longer proximal surgical edge (SMD - 0.51, 95% CI - 0.93 to - 0.09, P < 0.05; chi-square = 2.42). No significant difference was found in other indexes. After we removed a single large study, we performed another meta-analysis again. The operation duration in the SILS group was still better than that in the CLS group. CONCLUSION: SILS could be a faster and more reliable approach than CLS for the right colon cancer and could accelerate patient recovery, especially for patients with a low BMI.

Detection of alpha- and betacoronaviruses in rodents from Yunnan, China.

BACKGROUND: Rodents represent the most diverse mammals on the planet and are important reservoirs of human pathogens. Coronaviruses infect various animals, but to date, relatively few coronaviruses have been identified in rodents worldwide. The evolution and ecology of coronaviruses in rodent have not been fully investigated. RESULTS: In this study, we collected 177 intestinal samples from thress species of rodents in Jianchuan County, Yunnan Province, China. Alphacoronavirus and betacoronavirus were detected in 23 rodent samples from three species, namely Apodemus chevrieri (21/98), Eothenomys fidelis (1/62), and Apodemus ilex (1/17). We further characterized the full-length genome of an alphacoronavirus from the A. chevrieri rat and named it as AcCoV-JC34. The AcCoV-JC34 genome was 27,649 nucleotides long and showed a structure similar to the HKU2 bat coronavirus. Comparing the normal transcription regulatory sequence (TRS), 3 variant TRS sequences upstream the spike (S), ORF3, and ORF8 genes were found in the genome of AcCoV-JC34. In the conserved replicase domains, AcCoV-JC34 was most closely related to Rattus norvegicus coronavirus LNRV but diverged from other alphacoronaviruses, indicating that AcCoV-JC34 and LNRV may represent a novel alphacoronavirus species. However, the S and nucleocapsid proteins showed low similarity to those of LRNV, with 66.5 and 77.4% identities, respectively. Phylogenetic analysis revealed that the S genes of AcCoV-JC34, LRNV, and HKU2 formed a distinct lineage with all known coronaviruses. CONCLUSIONS: Both alphacoronaviruses and betacoronaviruses were detected in Apodemus chevrieri in the Yunnan Province of China, indicating that Apodemus chevrieri is an important host for coronavirus. Several new features were identified in the genome of an Apodemus chevrieri coronavirus. The phylogenetic distance to other coronaviruses suggests a variable origin and evolutionary route of the S genes of AcCoV-JC34, LRNV, and HKU2. These results indicate that the diversity of rodent coronaviruses is much higher than previously expected. Further surveillance and functional studies of these coronaviruses will help to better understand the importance of rodent as host for coronaviruses.

Severe Acute Respiratory Syndrome (SARS) Coronavirus ORF8 Protein Is Acquired from SARS-Related Coronavirus from Greater Horseshoe Bats through Recombination.

UNLABELLED: Despite the identification of horseshoe bats as the reservoir of severe acute respiratory syndrome (SARS)-related coronaviruses (SARSr-CoVs), the origin of SARS-CoV ORF8, which contains the 29-nucleotide signature deletion among human strains, remains obscure. Although two SARS-related Rhinolophus sinicus bat CoVs (SARSr-Rs-BatCoVs) previously detected in Chinese horseshoe bats (Rhinolophus sinicus) in Yunnan, RsSHC014 and Rs3367, possessed 95% genome identities to human and civet SARSr-CoVs, their ORF8 protein exhibited only 32.2 to 33% amino acid identities to that of human/civet SARSr-CoVs. To elucidate the origin of SARS-CoV ORF8, we sampled 348 bats of various species in Yunnan, among which diverse alphacoronaviruses and betacoronaviruses, including potentially novel CoVs, were identified, with some showing potential interspecies transmission. The genomes of two betacoronaviruses, SARSr-Rf-BatCoV YNLF_31C and YNLF_34C, from greater horseshoe bats (Rhinolophus ferrumequinum), possessed 93% nucleotide identities to human/civet SARSr-CoV genomes. Although these two betacoronaviruses displayed lower similarities than SARSr-Rs-BatCoV RsSHC014 and Rs3367 in S protein to civet SARSr-CoVs, their ORF8 proteins demonstrated exceptionally high (80.4 to 81.3%) amino acid identities to that of human/civet SARSr-CoVs, compared to SARSr-BatCoVs from other horseshoe bats (23.2 to 37.3%). Potential recombination events were identified around ORF8 between SARSr-Rf-BatCoVs and SARSr-Rs-BatCoVs, leading to the generation of civet SARSr-CoVs. The expression of ORF8 subgenomic mRNA suggested that the ORF8 protein may be functional in SARSr-Rf-BatCoVs. The high Ka/Ks ratio among human SARS-CoVs compared to that among SARSr-BatCoVs supported that ORF8 is under strong positive selection during animal-to-human transmission. Molecular clock analysis using ORF1ab showed that SARSr-Rf-BatCoV YNLF_31C and YNLF_34C diverged from civet/human SARSr-CoVs in approximately 1990. SARS-CoV ORF8 originated from SARSr-CoVs of greater horseshoe bats through recombination, which may be important for animal-to-human transmission. IMPORTANCE: Although horseshoe bats are the primary reservoir of SARS-related coronaviruses (SARSr-CoVs), it is still unclear how these bat viruses have evolved to cross the species barrier to infect civets and humans. Most human SARS-CoV epidemic strains contain a signature 29-nucleotide deletion in ORF8, compared to civet SARSr-CoVs, suggesting that ORF8 may be important for interspecies transmission. However, the origin of SARS-CoV ORF8 remains obscure. In particular, SARSr-Rs-BatCoVs from Chinese horseshoe bats (Rhinolophus sinicus) exhibited <40% amino acid identities to human/civet SARS-CoV in the ORF8 protein. We detected diverse alphacoronaviruses and betacoronaviruses among various bat species in Yunnan, China, including two SARSr-Rf-BatCoVs from greater horseshoe bats that possessed ORF8 proteins with exceptionally high amino acid identities to that of human/civet SARSr-CoVs. We demonstrated recombination events around ORF8 between SARSr-Rf-BatCoVs and SARSr-Rs-BatCoVs, leading to the generation of civet SARSr-CoVs. Our findings offer insight into the evolutionary origin of SARS-CoV ORF8 protein, which was likely acquired from SARSr-CoVs of greater horseshoe bats through recombination.

Fugong virus, a novel hantavirus harbored by the small oriental vole (Eothenomys eleusis) in China.

BACKGROUND: Rodents are natural reservoirs of hantaviruses, which cause two disease types: hemorrhagic fever with renal syndrome in Eurasia and hantavirus pulmonary syndrome in North America. Hantaviruses related human cases have been observed throughout Asia, Europe, Africa, and North America. To date, 23 distinct species of hantaviruses, hosted by reservoir, have been identified. However, the diversity and number of hantaviruses are likely underestimated in China, and hantavirus species that cause disease in many regions, including Yunnan province, are unknown. RESULTS: In August 2012, we collected tissue samples from 189 captured animals, including 15 species belonging to 10 genera, 5 families, and 4 orders in Fugong county, Yunnan province, China. Seven species were positive for hantavirus: Eothenomys eleusis (42/94), Apodemus peninsulae (3/25), Niviventer eha (3/27), Cryptotis montivaga (2/8), Anourosorex squamipes (1/1), Sorex araneus (1/1), and Mustela sibirica (1/2). We characterized one full-length genomic sequence of the virus (named fugong virus, FUGV) from a small oriental vole (Eothenomys eleusis). The full-length sequences of the small, medium, and large segments of FUGV were 1813, 3630, and 6531 nt, respectively. FUGV was most closely related to hantavirus LX309, a previously reported species detected in the red-backed vole in Luxi county, Yunnan province, China. However, the amino acid sequences of nucleocapsid (N), glycoprotein (G), and large protein (L) were highly divergent from those of Hantavirus LX309, with amino acid differences of 11.2, 15.3, and 12.7 %, respectively. In phylogenetic trees, FUGV clustered in the lineage corresponding to hantaviruses carried by rodents in the subfamily Arvicolinae. CONCLUSIONS: High prevalence of hantavirus infection in small mammals was found in Fugong county, Yunnan province, China. A novel hantavirus species FUGV was identified from the small oriental vole. This virus is phylogenetic clustering with another hantavirus LX309, but shows highly genomic divergence.

Effect of CYP3A4*1G, CYP3A5*3, POR*28, and ABCB1 C3435T on the pharmacokinetics of nifedipine in healthy Chinese volunteers.

OBJECTIVE: Nifedipine is a calcium channel blocker that is widely used in the treatment of cardiovascular disease. However, significant individual variances in the disposition of nifedipine have been reported, and genetic factors are considered to play an important role. The aim of the present study was to investigate the effect of CYP3A4*1G, CYP3A5*3, ABCB1-C3435T, and POR*28 genetic polymorphisms on nifedipine pharmacokinetics in healthy Chinese volunteers. METHODS: 45 healthy Chinese volunteers enrolled in this study received a single oral dose of 90 mg nifedipine after providing written informed consent. Volunteers were genotyped for CYP3A4*1G, CYP3A5*3, POR*28, and ABCB1-C3435T. The blood concentrations of nifedipine were determined by high performance liquid chromatography tandem mass spectrometry (LC-MS/MS) method. RESULTS AND DISCUSSION: There were significant differences of AUC00-∞ and AUC0-48h in the different CYP3A5*3 genotype groups (p = 0.043 and p = 0.048, respectively). The CYP3A5*3 GG group and POR*28 CT/TT group were found to have lower AUC00-∞ and Cmax compared with the POR*28 CC group (p = 0.046 and p = 0.002, respectively). In addition, the POR*28 CT/TT group was found to have longer t1/2 but lower Cmax than the CYP3A4*1G GG group (p = 0.032 and p = 0.002, respectively) as well as the CYP3A4*1G GG and the CYP3A5*3 GG group (p = 0.038 and p = 0.036, respectively) compared with the POR*28 CC group. No significant associations were found between CYP3A4*1G/ABCB1-C3435T polymorphism and pharmacokinetics of nifedipine. CONCLUSION: Both CYP3A5*3 and POR*28 polymorphisms are found to be associated with the difference in disposition of nifedipine; POR*28 is considered to have an impact on CYP3A4 activity.

Molecular epidemiology of reemergent rabies in Yunnan Province, southwestern China.

Yunnan Province in China borders 3 countries (Vietnam, Laos, and Myanmar) in Southeast Asia. In the 1980s, a large-scale rabies epidemic occurred in this province, which subsided by the late 1990s. However, 3 human cases of rabies in 2000 indicated reemergence of the disease in 1 county. In 2012, rabies was detected in 77 counties; 663 persons died of rabies during this new epidemic. Fifty two rabies virus strains obtained during 2008-2012 were identified and analyzed phylogenetically by sequencing the nucleoprotein gene. Of the 4 clades identified, clades YN-A and YN-C were closely related to strains from neighboring provinces, and clade YN-B was closely related to strains from Southeast Asia, but formed a distinct branch. Rabies virus diversity might be attributed to dog movements among counties, provinces, and neighboring countries. These findings suggest that Yunnan Province is a focal point for spread of rabies between Southeast Asia and China.

Molecular epidemiological study of Scrub Typhus in residence, farm and forest habitats from Yunnan Province, China.

The number of people suffering from scrub typhus, which is not of concern, is increasing year by year, especially in Yunnan Province, China. From June 1, 2021 to August 15, 2022, a total of 505 mammalian samples were collected from farm, forest, and residential habitats with high incidence of scrub typhus in Yunnan, China, for nPCR (nested PCR) and qPCR (quantitative real-time PCR) detection of Orientia tsutsugamushi. A total of 4 orders of murine-like animals, Rodentia (87.52%, n = 442), Insectivora (10.29%, n = 52), Lagomorpha (1.79%, n = 9) and Scandentia (0.40%, n = 2) were trapped. Comparing the qPCR infection rates in the three habitats, it was no significant difference that the infection rate of residential habitat (44.44%) and that of the farm habitat (45.05%, P>0.05), which is much larger than that of the forest habitat (3.08%) (P<0.001). Three genotypes (Karp-like, Kato-like and TA763-like) of O. tsutsugamushi were found from Yunnan, China in this study.

Metagenomic analysis of individual mosquito viromes reveals the geographical patterns and drivers of viral diversity.

Mosquito transmitted viruses are responsible for an increasing burden of human disease. Despite this, little is known about the diversity and ecology of viruses within individual mosquito hosts. Here, using a meta-transcriptomic approach, we determined the viromes of 2,438 individual mosquitoes (81 species), spanning ~4,000 km along latitudes and longitudes in China. From these data we identified 393 viral species associated with mosquitoes, including 7 (putative) species of arthropod-borne viruses (that is, arboviruses). We identified potential mosquito species and geographic hotspots of viral diversity and arbovirus occurrence, and demonstrated that the composition of individual mosquito viromes was strongly associated with host phylogeny. Our data revealed a large number of viruses shared among mosquito species or genera, enhancing our understanding of the host specificity of insect-associated viruses. We also detected multiple virus species that were widespread throughout the country, perhaps reflecting long-distance mosquito dispersal. Together, these results greatly expand the known mosquito virome, linked viral diversity at the scale of individual insects to that at a country-wide scale, and offered unique insights into the biogeography and diversity of viruses in insect vectors.

GW/P-bodies and autoimmune disease.

Human autoantibodies have performed admirably in the service of characterizing GW/P-bodies. These antibodies have provided a critical point of reference by which other proteins have been shown to be components of GW/P-bodies. In addition,autoantibodies have been used to identify new GW/P-body components, including Ge-l, GW182, RAP55, and YB-1. Using new, high-throughput screening assays, it is likely that additional, novel GW/P-body components will be identified. Human auto antibodies have also raised the possibility of a functional link between two apparently unrelated cellular structures, PML-SplOO nuclear bodies and GW/P-bodies.A key unanswered question remains: What is the role of GW/P-bodies in the pathogenesis of autoimmune disease? Over the next 10 years, as more is learned about the function of GW/P-bodies, it is hoped that molecular and cellular biologists will further consider this question and remember the important contributions of patients with autoimmune disease to the early characterization of these cellular structures.

Sclerotherapy for congenital vascular malformations with mixing foam of polidocanol and liquid of bleomycin.

OBJECTIVE: To evaluate the efficacy of sclerotherapy for congenital vascular malformation (CVM) using a combination of polidocanol foam and bleomycin liquid. METHODS: A retrospective review of a prospectively collected data on patients who had sclerotherapy for CVM from May 2015 to July 2022 was performed. RESULTS: A total of 210 patients with a mean age of 24.8 ± 2.0 years were included. Venous malformation (VM) was the most common type of CVM, accounting for 81.9% (172/210) of all patients. At 6 months follow-up, the overall clinical effective rate was 93.3% (196/210), and 50% (105/210) of patients were clinically cured. The clinical effective rates in VM, lymphatic, and arteriovenous malformation group were 94.2%, 100%, and 100%. CONCLUSION: Sclerotherapy using a combination of polidocanol foam and bleomycin liquid is an effective and safe treatment for venous and lymphatic malformations. It is a promising treatment option with satisfactory clinical outcome in arteriovenous malformations.

Repressing IRS1/2 by NT157 inhibits the malignant behaviors of ovarian cancer through inactivating PI3K/AKT/mTOR pathway and inducing autophagy.

Insulin receptor substrate 1 and 2 (IRS1/2) have been found involved in many cancers development and their inhibitors exert significant tumor-suppressive effects. Here, we tried to explore the function of NT157, an IGF1R-IRS1/2 inhibitor, in ovarian cancer. We treated ovarian cancer cells with varying doses of NT157. The MTT assay was employed to evaluate cell proliferation and colony formation assay was used for detecting colony-forming ability. TUNEL assay was adopted to test cell apoptosis. Cell invasion was checked by the Transwell assay. The expression of apoptosis-related proteins, autophagy markers, IRS1/2, and PI3K/AKT/mTOR pathway was compared by Western blot, immunofluorescence, or qRT-PCR. As indicated by the data, NT157 abated the viability, proliferation, and induced autophagy of ovarian cancer cells. Overexpressing IRS1/2 attenuated the tumor-suppressive effect of NT157 and heightened the PI3K/AKT/mTOR pathway activation. Inhibition of the PI3K/AKT/mTOR pathway enhanced the tumor-suppressive effect of NT157 and facilitated NT157-mediated autophagy. However, the autophagy inhibitor 3-MA partly reversed NT-157-mediated antitumor effects. In conclusion, this study disclosed that NT157 suppressed the malignant phenotypes of ovarian cancer cells by inducing autophagy and hampering the expression of IRS1/2 and PI3K/AKT/mTOR pathway.

Individual bat virome analysis reveals co-infection and spillover among bats and virus zoonotic potential.

Bats are reservoir hosts for many zoonotic viruses. Despite this, relatively little is known about the diversity and abundance of viruses within individual bats, and hence the frequency of virus co-infection and spillover among them. We characterize the mammal-associated viruses in 149 individual bats sampled from Yunnan province, China, using an unbiased meta-transcriptomics approach. This reveals a high frequency of virus co-infection (simultaneous infection of bat individuals by multiple viral species) and spillover among the animals studied, which may in turn facilitate virus recombination and reassortment. Of note, we identify five viral species that are likely to be pathogenic to humans or livestock, based on phylogenetic relatedness to known pathogens or in vitro receptor binding assays. This includes a novel recombinant SARS-like coronavirus that is closely related to both SARS-CoV and SARS-CoV-2. In vitro assays indicate that this recombinant virus can utilize the human ACE2 receptor such that it is likely to be of increased emergence risk. Our study highlights the common occurrence of co-infection and spillover of bat viruses and their implications for virus emergence.

Metagenomic analysis of individual mosquitos reveals the ecology of insect viruses.

Mosquito transmitted viruses are responsible for an increasing burden of human disease. Despite this, little is known about the diversity and ecology of viruses within individual mosquito hosts. Using a meta-transcriptomic approach, we analysed the virome of 2,438 individual mosquitos (79 species), spanning ~4000 km along latitudes and longitudes in China. From these data we identified 393 core viral species associated with mosquitos, including seven (putative) arbovirus species. We identified potential species and geographic hotspots of viral richness and arbovirus occurrence, and demonstrated that host phylogeny had a strong impact on the composition of individual mosquito viromes. Our data revealed a large number of viruses shared among mosquito species or genera, expanding our knowledge of host specificity of insect-associated viruses. We also detected multiple virus species that were widespread throughout the country, possibly facilitated by long-distance mosquito migrations. Together, our results greatly expand the known mosquito virome, linked the viral diversity at the scale of individual insects to that at a country-wide scale, and offered unique insights into the ecology of viruses of insect vectors.

Identification and characterization of protein interactions in the mammalian mRNA processing body using a novel two-hybrid assay.

Components of the mRNA processing body (P-body) regulate critical steps in mRNA storage, transport, translation and degradation. At the core of the P-body is the decapping complex, which removes the 5' cap from de-adenylated mRNAs and mediates an irreversible step in mRNA degradation. The assembly of P-bodies in Saccharomyces cerevisiae, Arabidopsis thaliana and Drosophila melanogaster has been previously described. Less is known about the assembly of mammalian P-bodies. To investigate the interactions that occur between components of mammalian P-bodies, we developed a fluorescence-based, two-hybrid assay system. The assay depends on the ability of one P-body component, fused to an exogenous nuclear localization sequence (NLS), to recruit other P-body components to the nucleus. The assay was used to investigate interactions between P-body components Ge-1, DCP2, DCP1, EDC3, RAP55, and RCK. The results of this study show that the modified two-hybrid assay can be used to identify protein interactions that occur in a macromolecular complex. The assay can also be used to efficiently detect protein interaction domains. The results provide important insights into mammalian P-body assembly and demonstrate similarities, and critical differences, between P-body assembly in mammalian cells compared with that of other species.

A time-series meta-transcriptomic analysis reveals the seasonal, host, and gender structure of mosquito viromes.

Although metagenomic sequencing has revealed high numbers of viruses in mosquitoes sampled globally, our understanding of how their diversity and abundance varies in time and space as well as by host species and gender remains unclear. To address this, we collected 23,109 mosquitoes over the course of 12 months from a bat-dwelling cave and a nearby village in Yunnan province, China. These samples were organized by mosquito species, mosquito gender, and sampling time for meta-transcriptomic sequencing. A total of 162 eukaryotic virus species were identified, of which 101 were novel, including representatives of seventeen RNA virus multi-family supergroups and four species of DNA virus from the families Parvoviridae, Circoviridae, and Nudiviridae. In addition, two known vector-borne viruses-Japanese encephalitis virus and Banna virus-were found. Analyses of the entire virome revealed strikingly different viral compositions and abundance levels in warmer compared to colder months, a strong host structure at the level of mosquito species, and no substantial differences between those viruses harbored by male and female mosquitoes. At the scale of individual viruses, some were found to be ubiquitous throughout the year and across four mosquito species, while most of the other viruses were season and/or host specific. Collectively, this study reveals the diversity, dynamics, and evolution of the mosquito virome at a single location and sheds new lights on the ecology of these important vector animals.

Individual bat viromes reveal the co-infection, spillover and emergence risk of potential zoonotic viruses.

Bats are reservoir hosts for many zoonotic viruses. Despite this, relatively little is known about the diversity and abundance of viruses within bats at the level of individual animals, and hence the frequency of virus co-infection and inter-species transmission. Using an unbiased meta-transcriptomics approach we characterised the mammalian associated viruses present in 149 individual bats sampled from Yunnan province, China. This revealed a high frequency of virus co-infection and species spillover among the animals studied, with 12 viruses shared among different bat species, which in turn facilitates virus recombination and reassortment. Of note, we identified five viral species that are likely to be pathogenic to humans or livestock, including a novel recombinant SARS-like coronavirus that is closely related to both SARS-CoV-2 and SARS-CoV, with only five amino acid differences between its receptor-binding domain sequence and that of the earliest sequences of SARS-CoV-2. Functional analysis predicts that this recombinant coronavirus can utilize the human ACE2 receptor such that it is likely to be of high zoonotic risk. Our study highlights the common occurrence of inter-species transmission and co-infection of bat viruses, as well as their implications for virus emergence.

PML nuclear body component Sp140 is a novel autoantigen in primary biliary cirrhosis.

OBJECTIVES: Some patients with primary biliary cirrhosis (PBC) have antinuclear antibodies (ANAs). These ANAs include the "multiple nuclear dots" (MND) staining pattern, targeting promyelocytic leukemia protein (PML) nuclear body (NB) components, such as "speckled 100-kD" protein (Sp100) and PML. A new PML NB protein, designated as Sp140, was identified using serum from a PBC patient. The aim of this study was to analyze the immune response against Sp140 protein in PBC patients. METHODS: We studied 135 PBC patients and 157 pathological controls with type 1 autoimmune hepatitis, primary sclerosing cholangitis, and systemic lupus erythematosus. We used indirect immunofluorescence and a neuroblastoma cell line expressing Sp140 for detecting anti-Sp140 antibodies, and a commercially available immunoblot for detecting anti-Sp100 and anti-PML antibodies. RESULTS: Anti-Sp140 antibodies were present in 20 (15%) PBC patients but not in control samples, with a higher frequency in antimitochondrial antibody (AMA)-negative cases (53 vs. 9%, P<0.0001). Anti-Sp140 antibodies were found together with anti-Sp100 antibodies in all but one case (19 of 20, 90%) and with anti-PML antibodies in 12 (60%) cases. Anti-Sp140 positivity was not associated with a specific clinical feature of PBC. CONCLUSIONS: Our study identifies Sp140 as a new, highly specific autoantigen in PBC for the first time. The very frequent coexistence of anti-Sp140, anti-Sp100 and anti-PML antibodies suggests that the NB is a multiantigenic complex in PBC and enhances the diagnostic significance of these reactivities, which are particularly useful in AMA-negative cases.