Prohibitin mediates the cellular invasion of spring viremia of the carp virus.

Spring viremia of carp virus (SVCV) is strongly contagious and pathogenic to common carp and cyprinoid species. However, knowledge of how SVCV enters host cells is still inadequate. In this study, mass spectrometry (MS) was incorporated with tandem affinity purification (TAP) to identify host proteins that interact with SVCV glycoprotein, the main attachment protein of SVCV. Specifically, prohibitin (PHB) received the utmost attention from all the candidate proteins, and its interaction with the SVCV-G protein was confirmed by immunoprecipitation and immunofluorescence assays. Treatment with PHB-specific inhibitors or knockdown of the expression of PHB by siRNAs resulted in a marked reduction in binding and entry of SVCV on host cells, while overexpression of PHB increased SVCV attachment and invasion. Furthermore, binding of SVCV to ZF4 and FHM cells was inhibited by pre-incubating the virus with recombinant PHB protein (rPHB) or blocking the cell surface PHB with its polyclonal antibodies. In addition, overexpression of PHB on SVCV-nonpermissive Grouper spleen cells (GSs) conferred susceptibility to SVCV infection. In vivo, treatment of rPHB could significantly inhibit SVCV propagation within zebrafish and benefit the survival rate of SVCV-infected zebrafish. These results demonstrate that PHB plays a crucial role in both the attachment and entry stages of SVCV infection.

STUB1 activates antiviral response in zebrafish by promoting the expression of RIG-I.

Spring viraemia of carp virus (SVCV) is a fierce pathogen causing high mortality in the common carp. At present, the treatment of spring viraemia of carp (SVC) is limited. Innate immunity is the host's first line of defense against microbial pathogens. Retinoic acid-inducible gene I (RIG-I) activation plays an essential role in the antiviral immune response. Virus infection can activate the RIG-I signaling and induce the production of interferon (IFN) and the expression of IFN-stimulated genes (ISGs). STUB1 (STIP1 homology and U-box containing protein 1) is a highly conserved cytoplasmic protein. This protein is known to exist widely in many biological systems and plays an important role in the process of immune regulation, but little is known in fish. To explore the immune function of STUB1 in fish, STUB1 gene was cloned from zebrafish and analyzed in this study. Zebrafish STUB1 showed 77% and 79% amino acid sequence homology with those from human and mouse, respectively. The amino acid sequence of zebrafish STUB1 contains three TPR domains and one U-box domain. Subcellular localization study revealed that STUB1 is located in the cytoplasm. And overexpression of zebrafish STUB1 resulted in the activation of the transcription of IFN1 and ISGs. Functional analysis showed that STUB1 was able to activate RIG-I signaling, and promote the expression of RIG-I, but STUB1 can degrade RIG-I in mammals. The proliferation of SVCV was significantly inhibited after the overexpression of STUB1 and N-terminal TPR domain of STUB1 in EPC cells. And through secondary structure analysis, overexpression of the mutant of STUB1 110 amino acid resulted in weakened antiviral ability. The expression of STUB1 was attenuated by poly(I:C) treatment and SVCV infection. In summary, this study demonstrated for the first time that STUB1 can induce the production of IFN, enhance the expression of ISGs by promoting the expression of RIG-I and inhibiting viral replication in fish. These findings may form the essential basis for the development of antiviral targets and drugs.

Zebrafish NIK Mediates IFN Induction by Regulating Activation of IRF3 and NF-κB.

Type I IFN mediates the innate immune system to provide defense against viral infections. NF-κB-inducing kinase (NIK) potentiates the basal activation of endogenous STING, which facilitates the recruitment of TBK1 with the ectopically expressed IRF3 to induce IFN production. Moreover, NIK phosphorylates IKKα and confers its ability to phosphorylate p100 (also known as NF-κB2) in mammals. Our study demonstrated that NIK plays a critical role in IFN production in teleost fish. It was found that NIK interacts with IKKα in the cytoplasm and that IKKα phosphorylates the NIK at the residue Thr432, which is different from the mammals. Overexpression of NIK caused the activation of IRF3 and NF-κB, which in turn led to the production of IFN and IFN-stimulated genes (ISGs). Furthermore, the ectopic expression of NIK was observed to be associated with a reduced replication of the fish virus, whereas silencing of endogenous NIK had an opposite effect in vitro. Furthermore, NIK knockdown significantly reduced the expression of IFN and key ISGs in zebrafish larvae after spring viremia of carp virus infection. Additionally, the replication of spring viremia of carp virus was enhanced in NIK knockdown zebrafish larvae, leading to a lower survival rate. In summary, our findings revealed a previously undescribed function of NIK in activating IFN and ISGs as a host antiviral response. These findings may facilitate the establishment of antiviral therapy to combat fish viruses.

Analysis of medical resources for allocation equity using traditional Chinese medicine resource as a model.

OBJECTIVES: This study is designed to analyse current allocation equity of medical resources in China for a better distribution of medical resources. METHODS: Descriptive statistical methods were used to analyse the overall allocation of Traditional Chinese medicine (TCM) resources between 2012 and 2018. Lorentz curve and Gini coefficient were used to quantitatively analyse the fairness of the allocation from the population and geography two dimensions. RESULTS: This study revealed an increase of TCM resources for the 6-year period, but the fair allocation of these resources was subjected to the methods used. The Gini coefficients were <0.3 based on population distribution but >0.5 basing on the geography allocation. CONCLUSION: Population based analysis for the equity of the TCM resource allocation is superior, more attention for health resource planning is needed to focus on geographical fairness in the future, especially for the less populated rural regions.

Short-term effects of ambient air pollution on the incidence of influenza in Wuhan, China: A time-series analysis.

BACKGROUND: Evidence suggests that air pollution is associated with many adverse health outcomes such as cardiovascular diseases (CVD), respiratory diseases, cancer, and birth defects. Yet few studies dig into the relationship between air pollution and airborne infectious diseases. METHODS: Daily data on influenza incidence were obtained from Hubei Provincial Center for Disease Control and Prevention (Hubei CDC). Data on air pollutants including nitrogen dioxide (NO2), sulfur dioxide (SO2), ground-level ozone (O3), particulate matter (PM) with aerodynamic diameter ≤ 2.5 µm (PM2.5), and PM with aerodynamic diameter ≤ 10 µm (PM10) were retrieved from ten national air sampling stations located at Wuhan. We applied generalized additive model (GAM) to estimate the associations between air pollution and the risk of influenza in Wuhan, China during 2015-2017. RESULTS: In the single-day lag model, the largest effect estimates were observed at lag 0. An increased relative risk (RR) of influenza was significantly associated with a 10 µg/m3 increase in SO2 (RR: 1.099; 95% confidence interval [CI]: 1.011-1.195), NO2 (RR: 1.039; 95% CI: 1.013-1.065), and O3 (RR: 1.005; 95% CI: 0.994-1.016), respectively. In the multi-day lag model, concentrations of SO2, NO2, and O3 were statistically significantly associated with the risk of influenza at lag 0-1. The seasonal analysis suggests that the influence of air pollution on influenza is greater in the cold season as compared in the warm season in the early lag days. The multi-pollutant model indicates that NO2 may be a potential confounder for co-pollutants. CONCLUSIONS: Our study shows that air pollution may be associated with the risk of influenza in a broad sense. Therefore, when formulating policies to deal with influenza outbreaks in the future, factors regarding air pollution should be taken into consideration.

Equity analysis of Chinese physician allocation based on Gini coefficient and Theil index.

BACKGROUND: Unequal allocation of medical physician resource represents one of major problems in the current medical service management in China and many other countries. This study is designed to analyze the current distribution of physicians in 31 provincial administrative regions in China, to estimate the fairness of the distribution of physicians and provide a theoretical basis for the improvement of the allocation of physicians. METHODS: This study took physicians from 31 provincial administrative regions in China as the study objects, and the data were obtained from the China Health Statistics Yearbook 2019 and the official website of the National Bureau of Statistics of China. Calculation of the Gini coefficient (G) and the Theil index (T) were carried out by drawing the Lorenz curve. The fairness of present physician location in 31 provincial administrative regions in China was analyzed from the perspective of distribution by both population and service area. RESULTS: The Gini coefficients of medical physicians in China are 0.003 and 0.88 by population and by service area, respectively. This shows that the distribution of medical physicians is fair basing on population, and there is little difference in the number of physicians per 1000 population in different regions. However, the physician distribution basing on service area is highly unfair and shows a large gap in the number of physicians per square kilometer between different regions. In general, Beijing, Zhejiang, Shanghai, Jiangsu, Shandong, and Tianjin are higher than the overall level of 31 provincial administrative regions. In addition, the number of medical physicians in Zhejiang, Shandong, Beijing and Jiangsu is over-provisioned. CONCLUSION: Bridging the number of medical physicians in different regions is a key step to improve the equity of physicians' resource allocation. Thus, findings from this study emphasize the need to take more measures to reduce physician quality differences between regions, balance and coordinate medical resources. This will increase the access of all citizens to quality medical services.

A Lymphoid Organ Specific Anti-Lipopolysaccharide Factor from Litopenaeus vannamei Exhibits Strong Antimicrobial Activities.

Different shrimp species are known to possess apparent distinct resistance to different pathogens in aquaculture. However, the molecular mechanism underlying this finding still remains unknown. One kind of important antimicrobial peptides, anti-lipopolysaccharide factors (ALF), exhibit broad-spectrum antimicrobial activities. Here, we reported a newly identified ALF from the shrimp Litopenaeus vannamei and compared the immune function with its counterpart in the shrimp Fenneropenaeus chinensis. The ALF, designated as LvALF8, was specifically expressed in the lymphoid organ of L. vannamei. The expression level of LvALF8 was apparently changed after white spot syndrome virus (WSSV) or Vibrio parahaemolyticus challenges. The synthetic LBD peptide of LvALF8 (LvALF8-LBD) showed strong antibacterial activities against most tested Gram-negative and Gram-positive bacteria. LvALF8-LBD could also inhibit the in vivo propagation of WSSV similar as FcALF8-LBD, the LBD of LvALF8 counterpart in F. chinensis. However, LvALF8-LBD and FcALF8-LBD exhibited apparently different antibacterial activity against V. parahaemolyticus, the main pathogen causing acute hepatopancreatic necrosis disease (AHPND) of affected shrimp. A structural analysis showed that the positive net charge and amphipathicity characteristics of LvALF8-LBD peptide were speculated as two important components for its enhanced antimicrobial activity compared to those of FcALF8-LBD. These new findings may not only provide some evidence to explain the distinct disease resistance among different shrimp species, but also lay out new research ground for the testing and development of LBD-originated antimicrobial peptides to control of shrimp diseases.

FTR67, a member of the fish-specific finTRIM family, triggers IFN pathway and against spring viremia of carp virus.

Tripartite motif (TRIM) proteins have attracted particular research interest because of their multiple functions in the antiviral innate immune response. TRIM proteins perform different functions during virus infection, some play a role in inhibiting while others play a role in promoting. In this study, we described a species-specific TRIM gene named ftr67. Analysis of tissue distribution showed that ftr67 was mainly expressed in the gill and liver in five examined tissues of zebrafish. The phylogenic analysis showed that ftr67 was closest to the grass carp TRIM67. Overexpression of ftr67 resulted in a significantly decreased SVCV entry and impaired SVCV replication in FHM cells. Furthermore, overexpression of ftr67 could significantly induce the upregulation of molecular sensor RIG-I, IRF3/7, IFN and ISGs. In addition, RING domain of ftr67 was a required part essential for the antiviral effect. In summary, our results demonstrated that the important role of ftr67 in regulating SVCV infection, which offers a potential target for development of anti-SVCV therapies.

Effects of ambient temperature and precipitation on the risk of dengue fever: A systematic review and updated meta-analysis.

OBJECTIVES: We systematically reviewed the published studies on the relationship between dengue fever and meteorological factors and applied a meta-analysis to explore the effects of ambient temperature and precipitation on dengue fever. METHODS: We completed the literature search by the end of September 1st, 2019 using databases including Science Direct, PubMed, Web of Science, and Google Scholar. We extracted relative risks (RRs) in selected studies and converted all effect estimates to the RRs per 1 °C increase in temperature and 10 mm increase in precipitation, and combined all standardized RRs together using random-effect meta-analysis. RESULTS: Our results show that dengue fever was significantly associated with both temperature and precipitation. Our subgroup analyses suggested that the effect of temperature on dengue fever was most pronounced in high-income subtropical areas. The pooled RR of dengue fever associated with the maximum temperature was much lower than the overall effect. CONCLUSIONS: Temperature and precipitation are important risk factors for dengue fever. Future studies should focus on factors that can distort the effects of temperature and precipitation.

Associations between long-term exposure to air pollution and blood pressure and effect modifications by behavioral factors.

BACKGROUND: Studies on the hypertensive effect of long-term air pollution exposure were inconclusive and showed scarce evidence from rural areas in developing countries. In this context, we examined the associations of air pollution exposure with hypertension and blood pressure, and their effect modifiers in rural Chinese adults. METHODS: We studied 39,259 participants from a cohort established in five rural regions of central China. Individual exposures to PM2.5 and PM10 (particulate matter with an aerodynamic diameter less than or equal to 2.5 µm and 10 µm) and nitrogen dioxide (NO2) was evaluated using satellite-based spatiotemporal models. Mixed-effect regression models were applied to examine the associations of long-term exposure to air pollution with hypertension and four blood pressure component measurements, including systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure (PP). Several potential effect modifiers related to demographic and behavioral factors were also examined. RESULTS: The results showed that for each 1 µg/m3 increase in PM2.5, PM10 and NO2, the adjusted odds ratio of hypertension was 1.029 (95%CI: 1.001,1.057), 1.015 (95%CI: 1.001, 1.029) and 1.069 (95%CI: 1.038, 1.100), respectively. These three air pollutants were also associated with increased SBP (except for PM10), DBP and MAP. The hypertensive effects of air pollution were more pronounced among males, smokers, drinkers, individuals with a high-fat diet, and those with high-level physical activity. CONCLUSION: Long-term exposure to PM2.5, PM10 and NO2 was associated with increased blood pressure and hypertension in rural Chinese adults, and the associations were modified by several behavioral factors.

Role of IL-9 and IL-10 in the pathogenesis of chronic spontaneous urticaria through the JAK/STAT signalling pathway.

This study investigated the role of interleukin (IL)-9 and IL-10 in the pathogenesis of chronic spontaneous urticaria (CSU). Autologous serum skin test and histamine release test were performed in CSU patients and normal subjects. Kunming mice were used to develop a mouse model for CSU. We induced IL-9 overexpression, IL-10 overexpression, and JAK/STAT pathway inhibition as well as a combination of all three conditions in CSU and control mice. Eosinophils in the skin tissues, inflammatory cytokine expression, and distribution of T lymphocyte subsets in peripheral blood of mice were detected. Expression patterns of IL-9, IL-10, STAT3, JAK2, and INF-γ in clinical samples and mice were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. The positive rate of autologous serum skin test and the histamine release rate of CSU patients, compared with normal subjects, were apparently elevated. Compared with controls, mice with CSU experienced longer duration and higher frequency of pruritus and demonstrated enhanced levels of CD8+ , the ratio of CD4+ /CD8+ , number of eosinophils, and inflammatory cytokine expression in serum as well as activated JAK/STAT signalling pathway; at the same time, levels of CD4+ and INF-γ were reduced. This trend was found in CSU mice overexpressing IL-9 and IL-10 when compared with the CSU mice without treatment. In contrast, JAK/STAT inhibition reversed the above trend. Overall, our study suggests that IL-9 and IL-10 contribute to CSU development via activation of the JAK/STAT signalling pathway.

Acute effect of ambient fine particulate matter on heart rate variability: an updated systematic review and meta-analysis of panel studies.

BACKGROUND: Decreased heart rate variability (HRV) is a predictor of autonomic system dysfunction, and is considered as a potential mechanism of increased risk of cardiovascular disease (CVD) induced by exposure to particulate matter less than 2.5 µm in diameter (PM2.5). Previous studies have suggested that exposure to PM2.5 may lead to decreased HRV levels, but the results remain inconsistent. METHODS: An updated systematic review and meta-analysis of panel studies till November 1, 2019 was conducted to evaluate the acute effect of exposure to ambient PM2.5 on HRV. We searched electronic databases (PubMed, Web of Science, and Embase) to identify panel studies reporting the associations between exposure to PM2.5 and the four indicators of HRV (standard deviation of all normal-to-normal intervals (SDNN), root mean square of successive differences in adjacent normal-to-normal intervals (rMSSD), high frequency power (HF), and low frequency power (LF)). Random-effects model was used to calculate the pooled effect estimates. RESULTS: A total of 33 panel studies were included in our meta-analysis, with 16 studies conducted in North America, 12 studies in Asia, and 5 studies in Europe. The pooled results showed a 10 µg/m3 increase in PM2.5 exposure which was significantly associated with a - 0.92% change in SDNN (95% confidence intervals (95%CI) - 1.26%, - 0.59%), - 1.47% change in rMSSD (95%CI - 2.17%, - 0.77%), - 2.17% change in HF (95%CI - 3.24%, - 1.10%), and - 1.52% change in LF (95%CI - 2.50%, - 0.54%), respectively. Overall, subgroup analysis suggested that short-term exposure to PM2.5 was associated with lower HRV levels in Asians, healthy population, and those aged ≥ 40 years. CONCLUSION: Short-term exposure to PM2.5 was associated with decreased HRV levels. Future studies are warranted to clarity the exact mechanism of exposure to PM2.5 on the cardiovascular system through disturbance of autonomic nervous function.

Fish-specific finTRIM FTR36 triggers IFN pathway and mediates inhibition of viral replication.

The tripartite motif (TRIM) family involves many cellular processes, including fundamental functions in antiviral immunity. Antiviral activities of TRIMs are reported in a variety of patterns, and one of the most significant channels is related to the activation of the type-I interferon (IFN) pathway. In this study, we described a fintrim (ftr) gene named ftr36, which is mainly expressed in the gills, skin, and intestines. This study shows that ftr36 encodes a protein affording a potent antiviral effect. In vitro, overexpression of FTR36 mediated an upregulated pattern of recognition receptor retinoic acid-inducible gene I (RIG-I), interferon regulatory factor 3/7(IRF3/7), IFN, and IFN-stimulated genes (ISGs) expression. Thereby, FTR36 expression could afford host defense against the spring viremia of carp virus (SVCV) and the giant salamander iridovirus (GSIV). With the deletion of the RING domain or B30.2 domain separately, the antiviral ability of FTR36 was abolished partially and almost lost its ability to activate the IFN-pathway. These findings indicate that both RING and B30.2 domains are indispensable for the antiviral activity of FTR36. Altogether, this study described a finTRIM FTR36, which can activate IFN-pathways and stimulate ISGs to provide host defense against viral infections.

The antiviral mechanism of viperin and its splice variant in spring viremia of carp virus infected fathead minnow cells.

Viperin is known to play an important role in innate immune and its antiviral mechanisms are well demonstrated in mammals. Fish Viperin mediates antiviral activity against several viruses. However, little has been done to the underlying mechanism. Here, we discovered a novel Viperin splice variant named Viperin_sv1 from viral-infected FHM cells. Spring varimia of carp virus (SVCV) was able to increase the mRNA levels of both Viperin and Viperin_sv1, while poly(I:C) only has effect on Viperin. Viperin functions as an antiviral protein at 24 h post-SVCV infection, but the antiviral activity dramatically declined at late infection stages. However, Viperin_sv1 inhibited SVCV replication significantly at all the tested time. Viperin_sv1, but not Viperin can facilitate the production of type I IFN and IFN stimulate genes (ISGs) through activation of RIG-1, IRF3 and IRF7 signaling cascades. On the other hand, SVCV down-regulated Viperin_sv1 at the protein level through the proteasome pathway to keep itself away from the immune system monitoring. Taken together, these findings provide new insights into the regulation of Viperin from the posttranscriptional modification perspective and the role of splicing variant Viperin_sv1 in virus-host interaction.

Identification of fish CMPK2 as an interferon stimulated gene against SVCV infection.

Cytidine/uridine monophosphate kinase 2 (CMPK2) is known as a nucleoside monophosphate kinase in mitochondria to maintains intracellular UTP/CTP, and could be induced by immunostimulants LPS and Poly (I:C) in mammals, suggesting its potential antiviral and antibacterial role. In this study, CMPK2 was cloned and characterized in Fathead minnow (FHM) cells. In vivo analysis of tissue distribution revealed that CMPK2 transcript was detected in all the tissues of zebrafish (Danio rerio) examined in this study, particularly abundant in liver, spleen and kidney. In addition, indirect immunofluorescence showed that CMPK2 was localized in the cytoplasm of FHM cells. Expression of CMPK2 mRNA was significantly up-regulated following challenge with Spring viraemia of carp virus (SVCV), poly(I:C), or zebrafish IFN1 and IFN3 both in vitro and in vivo. Furthermore, overexpression and RNA interference of CMPK2 in SVCV-infected FHM cells showed significantly antiviral effect. In summary, this study for the first time shows the presence and distribution of CMPK2 in different tissues of zebrafish, but also demonstrates its antiviral potential against SVCV infection in vivo. These new findings could contribute to explain the molecular mechanism of the CMPK2 mediated antiviral function.

The association between short-term exposure to ambient air pollution and the incidence of mumps in Wuhan, China: A time-series study.

BACKGROUND: Previous studies have estimated the association between meteorological factors and mumps outbreaks without assessing the influence of air pollution. In this research, we explored the effects of short-term exposure to air pollution on the incidence of mumps. METHODS: Our time-series analysis was conducted using data collected in Wuhan, China from 2015 to 2017. Daily number of mumps cases was obtained from Disease Reporting System in Hubei Provincial Center for Disease Control and Prevention. Data on air pollution was obtained from 10 national air quality monitoring stations, including nitrogen dioxide (NO2), sulfur dioxide (SO2), ground-level ozone (O3), particulate matter less than or equal to 10 µm in aerodynamic diameter (PM10), and particulate matter less than or equal to 2.5 µm in aerodynamic diameter (PM2.5). Daily meteorological data including temperature and relative humidity were obtained from Hubei Meteorological Bureau. We performed a Poisson regression in generalized additive models (GAM) to explore the association between the incidence of mumps and exposure to air pollution. RESULTS: We observed that the effects of air pollutants were statistically significant mainly in two periods, lag 0 to lag 5 and lag 20 to lag 25, with the strongest effects appearing at lag 2 and lag 23. The cumulative effects were stronger than single-day lag effects. The stratified analysis showed the effect of pollutants during the hot season was stronger than that during the cold season, especially for NO2 and SO2. CONCLUSIONS: We found that exposure to NO2 and SO2 was significantly associated with higher risk of developing mumps. Our findings could help deepen the understanding of how air pollution exposure affects the incidence of mumps.

Monitoring of Poyang lake water for sewage contamination using human enteric viruses as an indicator.

BACKGROUND: Recreational water contaminated with fecal pollution poses a great public health concern, as fecal waste may cause serious waterborne illnesses. Current recreational water standards using fecal indicator bacteria (FIB) have their limitations for human protection especially in developing countries such as China. METHODS: To explore the potential use of enteric viruses as a potential indicator of fecal contamination, four viruses: norovirus geno-groups I and II, enteroviruses, and adenoviruses were tested in this study using molecular detection methods and sensitive RT-PC developed in the University of Hawaii. Water samples were also tested for FIB in order to determine their association with enteric virus detection. RESULTS: All sample sites tested positive for four enteric viruses. Human enterovirus (58%) and adenovirus (67%) were more frequently detected from these six sites, followed by norovirus I (50%) and norovirus II (38%). Six sampling sites all met the level-I water quality of GB3838-2002 criteria in microbiological level, but they all tested positive for enteric viruses. CONCLUSION: These findings indicate the current sewage contamination of Poyang Lake and also support the essential need of additional indicator such as human enteric viruses for enhanced monitoring of water quality since the presence of enteric viruses does not always correlate with fecal bacterial indicator detection.

14-3-3ß/α-A interacts with glycoprotein of spring viremia of carp virus and positively affects viral entry.

Spring viremia of carp virus (SVCV) is a fierce pathogen causing high mortality in the common carp. The glycoprotein (G protein) of SVCV is a pivotal component of the viral structure, located in the surface of the virion, and plays a key role in viral endocytosis. In this study, tandem affinity purification (TAP) followed by mass spectrometry analysis (LC-MS/MS) was carried out to search for novel host molecules that interact with SVCV G protein and a 14-3-3ß/α-A protein was identified. The level of 14-3-3ß/α-A mRNA expression was dramatically down regulated by SVCV infection. Furthermore, over expression of 14-3-3ß/α-A results in a significantly increased SVCV attachment and entry in FHM cells. This study reveals an important role of 14-3-3 protein in regulating the early stage of SVCV infection, which offers a potential target for development of anti-SVCV therapies.

Human adenosine deaminases ADA1 and ADA2 bind to different subsets of immune cells.

At sites of inflammation and tumor growth, the local concentration of extracellular adenosine rapidly increases and plays a role in controlling the immune responses of nearby cells. Adenosine deaminases ADA1 and ADA2 (ADAs) decrease the level of adenosine by converting it to inosine, which serves as a negative feedback mechanism. Mutations in the genes encoding ADAs lead to impaired immune function, which suggests a crucial role for ADAs in immune system regulation. It is not clear why humans and other mammals possess two enzymes with adenosine deaminase activity. Here, we found that ADA2 binds to neutrophils, monocytes, NK cells and B cells that do not express CD26, a receptor for ADA1. Moreover, the analysis of CD4+ T-cell subset revealed that ADA2 specifically binds to regulatory T cells expressing CD39 and lacking the receptor for ADA1. Also, it was found that ADA1 binds to CD16- monocytes, while CD16+ monocytes preferably bind ADA2. A study of the blood samples from ADA2-deficient patients showed a dramatic reduction in the number of lymphocyte subsets and an increased concentration of TNF-α in plasma. Our results suggest the existence of a new mechanism, where the activation and survival of immune cells is regulated through the activities of ADA2 or ADA1 anchored to the cell surface.

Comparative transcriptome analysis of zebrafish (Danio rerio) brain and spleen infected with spring viremia of carp virus (SVCV).

Spring viremia of carp virus (SVCV) is the pathogen of spring viremia of carp (SVC) and often causes acute hemorrhagic symptoms in various kinds of cyprinids and induces serious environmental and economic losses. However, the molecular mechanisms of infection remain poorly understood, especially at the individual level. In this study, zebrafish was employed as the infection model to explore the pathogenesis of SVCV. 4 groups of zebrafish tissues were set and RNA sequencing (RNA-Seq) technology was employed to analyze the differentially expressed genes (DEGs) after SVCV-infection. A total of 360,971,498 clean reads were obtained from 12 samples, 382 DEGs in the brain and 926 DEGs in the spleen were identified. These DEGs were annotated into three ontologies after gene ontology (GO) enrichment analysis. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that these DEGs were primarily related to Influenza A pathway and Herpes simplex infection pathway in brain and Tuberculosis and Toxoplasmosis pathways in spleen, and all of these pathways may be involved in response to pathogen invasion. At the same time, 3' and 5' alternative splicing (AS) events were significantly up-regulated in the spleen. The transcriptome analysis results demonstrated changes and tissue-specific influences caused by SVCV in vivo, which provided us with more information to understand the complex relationships between SVCV and its host.