Immune Evasion of Mycoplasma gallisepticum: An Overview.

Mycoplasma gallisepticum is one of the smallest self-replicating organisms. It causes chronic respiratory disease, leading to significant economic losses in poultry industry. Following M. gallisepticum invasion, the pathogen can persist in the host owing to its immune evasion, resulting in long-term chronic infection. The strategies of immune evasion by mycoplasmas are very complex and recent research has unraveled these sophisticated mechanisms. The antigens of M. gallisepticum exhibit high-frequency changes in size and expression cycle, allowing them to evade the activation of the host humoral immune response. M. gallisepticum can invade non-phagocytic chicken cells and also regulate microRNAs to modulate cell proliferation, inflammation, and apoptosis in tracheal epithelial cells during the disease process. M. gallisepticum has been shown to transiently activate the inflammatory response and then inhibit it by suppressing key inflammatory mediators, avoiding being cleared. The regulation and activation of immune cells are important for host response against mycoplasma infection. However, M. gallisepticum has been shown to interfere with the functions of macrophages and lymphocytes, compromising their defense capabilities. In addition, the pathogen can cause immunological damage to organs by inducing an inflammatory response, cell apoptosis, and oxidative stress, leading to immunosuppression in the host. This review comprehensively summarizes these evasion tactics employed by M. gallisepticum, providing valuable insights into better prevention and control of mycoplasma infection.

Exploring the association between sexual motivation and quality of life in China and the United Kingdom.

Previous research suggests that different sexual motivations may be associated with different sexual behaviours and levels of sexual satisfaction, and these may vary with cultural differences. As such, sexual motivations and cultural factors might also be associated with quality of life (QoL); however, this has not yet been explored. Using a biopsychosocial approach, this study aimed to explore associations between sexual motivation and quality of life between participants in the United Kingdom and China. 276 participants (143 British, 133 Chinese, mean age = 21.5 years) completed an anonymous online survey including validated measures for sexual motivation (YSEX?-SF) and QoL (WHOQOL-BREF). In multivariable linear regressions, pleasure motivations for sex were associated with increased physical health QoL (aOR = 0.20, 95%CI:.15-.65), while love and commitment motivations were associated with increased psychological health QoL (aOR = 0.13, 95%CI:.01-.43). Both love and commitment motivations (aOR = 0.21, 95%CI:.09-.35) and pleasure motivations (aOR = 0.20, 95%CI:.08-.36) were associated with increased social support QoL. A significant interaction was found between emotional motivations and culture (p = 0.037) such that among individuals from China, emotional motivations (i.e., love and commitment and expression) were positively associated with psychological QoL. This suggests culture may differentially affect how sexual motivations are associated with QoL and warrants further consideration in future research.

Reduced NR2F2 Expression in the Host Response to Infectious Bursal Disease Virus Infection Suppressed Viral Replication by Enhancing Type I Interferon Expression by Targeting SOCS5.

Nuclear receptors are ligand-activated transcription factors that play an important role in regulating innate antiviral immunity and other biological processes. However, the role of nuclear receptors in the host response to infectious bursal disease virus (IBDV) infection remains elusive. In this study, we show that IBDV infection or poly(I·C) treatment of DF-1 or HD11 cells markedly decreased nuclear receptor subfamily 2 group F member 2 (NR2F2) expression. Surprisingly, knockdown, knockout, or inhibition of NR2F2 expression in host cells remarkably inhibited IBDV replication and promoted IBDV/poly(I·C)-induced type I interferon and interferon-stimulated genes expression. Furthermore, our data show that NR2F2 negatively regulates the antiviral innate immune response by promoting the suppressor of cytokine signaling 5 (SOCS5) expression. Thus, reduced NR2F2 expression in the host response to IBDV infection inhibited viral replication by enhancing the expression of type I interferon by targeting SOCS5. These findings reveal that NR2F2 plays a crucial role in antiviral innate immunity, furthering our understanding of the mechanism underlying the host response to viral infection. IMPORTANCE Infectious bursal disease (IBD) is an immunosuppressive disease causing considerable economic losses to the poultry industry worldwide. Nuclear receptors play an important role in regulating innate antiviral immunity. However, the role of nuclear receptors in the host response to IBD virus (IBDV) infection remains elusive. Here, we report that NR2F2 expression decreased in IBDV-infected cells, which consequently reduced SOCS5 expression, promoted type I interferon expression, and suppressed IBDV infection. Thus, NR2F2 serves as a negative factor in the host response to IBDV infection by regulating SOCS5 expression, and intervention in the NR2F2-mediated host response by specific inhibitors might be employed as a strategy for prevention and treatment of IBD.

Critical Role of Viral Protein Hexon in Hypervirulent Fowl Adenovirus Serotype-4-Induced Autophagy by Interaction with BAG3 and Promotion of Viral Replication in LMH Cells.

Hepatitis-pericardial syndrome (HHS) is an acute highly infectious avian disease caused by fowl adenovirus serotype 4 (FAdV-4), characterized by fulminant hepatitis and hydropericardium in broilers. Since 2015, a widespread epidemic has occurred in China due to the emergence of hypervirulent FAdV-4 (HPFAdV-4), causing huge losses to the stakeholders. However, the pathogenesis of HPFAdV-4 and the host responses to its infection remain elusive. Here, we show that infection of leghorn male hepatocellular (LMH) cells by HPFAdV-4 induced complete autophagy in cells and that the autophagy induced by recombinant HPFAdV-4-ON1 (rHPFAdV-4-ON1), a viral strain generated by replacing the hexon gene of wild-type HPFAdV-4 (HPFAdV-4-WT) with the one of nonpathogenic strain FAdV-4-ON1, was remarkably mitigated compared to that of the rHPFAdV-4-WT control, suggesting that HPFAdV-4 hexon is responsible for virus-induced autophagy. Importantly, we found that hexon interacted with a cellular protein, BAG3, a host protein that initiates autophagy, and that BAG3 expression increased in cells infected with HPFAdV-4. Furthermore, knockdown of BAG3 by RNA interference (RNAi) significantly inhibited HPFAdV-4- or hexon-induced autophagy and suppressed viral replication. On the contrary, expression of hexon markedly upregulated the expression of BAG3 via activating the P38 signaling pathway, triggering autophagy. Thus, these findings reveal that HPFAdV-4 hexon interacts with the host protein BAG3 and promotes BAG3 expression by activating P38 signaling pathway, thereby inducing autophagy and enhancing viral proliferation, which immensely furthers our understanding of the pathogenesis of HPFAdV-4 infection. IMPORTANCE HHS, mainly caused by HPFAdV-4, has caused large economic losses to the stakeholders in recent years. Infection of leghorn male hepatocellular (LMH) cells by HPFAdV-4 induced complete autophagy that is essential for HPFAdV-4 replication. By a screening strategy, the viral protein hexon was found responsible for virus-induced autophagy in cells. Importantly, hexon was identified as a factor promoting viral replication by interaction with BAG3, an initiator of host cell autophagy. These findings will help us to better understand the host response to HPFAdV-4 infection, providing a novel insight into the pathogenesis of HPFAdV-4 infection.

Genetic Insight into the Interaction of IBDV with Host-A Clue to the Development of Novel IBDV Vaccines.

Infectious bursal disease virus (IBDV) is an immunosuppressive pathogen causing enormous economic losses to the poultry industry across the globe. As a double-stranded RNA virus, IBDV undergoes genetic mutation or recombination in replication during circulation among flocks, leading to the generation and spread of variant or recombinant strains. In particular, the recent emergence of variant IBDV causes severe immunosuppression in chickens, affecting the efficacy of other vaccines. It seems that the genetic mutation of IBDV during the battle against host response is an effective strategy to help itself to survive. Therefore, a comprehensive understanding of the viral genome diversity will definitely help to develop effective measures for prevention and control of infectious bursal disease (IBD). In recent years, considerable progress has been made in understanding the relation of genetic mutation and genomic recombination of IBDV to its pathogenesis using the reverse genetic technique. Therefore, this review focuses on our current genetic insight into the IBDV's genetic typing and viral genomic variation.

MAPK4 predicts poor prognosis and facilitates the proliferation and migration of glioma through the AKT/mTOR pathway.

BACKGROUND: Mitogen-activated protein kinase 4 (MAPK4) is an atypical member of the mitogen-activated protein kinase (MAPK) family. We report here that MAPK4 is overexpressed in glioma. The clinical significance, biological roles and underlying molecular mechanisms through which MAPK4 acts in glioma remain unclear. METHODS: Analysis of MAPK4 expression and associated survival in glioma patients was performed based on data obtained from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases and confirmed in human glioma tissue by immunohistochemistry. MAPK4 function and pathway enrichment were analyzed through Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO). The viability and migration ability of MAPK4-silenced glioblastoma multiforme (GBM) cells were evaluated using CCK8 and transwell assays, respectively, and cell cycle and apoptosis analyses were performed using flow cytometry. Immunoblotting was used to analyze the protein level in MAPK4 knockdown glioma cells. We also analyzed the correlation of MAPK4 expression with immune infiltration and immune checkpoints in glioma. RESULTS: MAPK4 was overexpressed in IDH wild-type (wt) and 1p/19q non-codeletion gliomas. MAPK4 expression predicted poor prognosis of glioma patients. MAPK4 was significantly related to functional states, including stemness, metastasis, cell cycle, differentiation and proliferation, in glioma at single-cell resolution. MAPK4 silencing inhibited proliferation and migration and induced G1 cell cycle arrest in glioma cells via the AKT/mTOR pathway. In vivo, MAPK4 knockdown markedly suppressed the growth of primary glioma. In addition, MAPK4 expression correlated negatively with the infiltration of plasmacytoid DC cells, CD8+ T cells and T helper cells. Moreover, MAPK4 expression correlated positively with expression of the main immunoinhibitor checkpoint molecules and some chemokines in glioma. CONCLUSION: MAPK4 functions as a prognostic indicator in glioma and promotes the proliferation and migration of GBM cells through the AKT/mTOR pathway. MAPK4 may participate in immune infiltration and the expression of immune checkpoints in the glioma microenvironment.

Chicken infectious anemia virus (CIAV) VP1 antagonizes type I interferon (IFN-I) production by inhibiting TBK1 phosphorylation.

Chicken infectious anemia virus (CIAV) infection induces immunosuppression or subclinical immunosuppression in chickens. CIAV infection has been reported to repress type I interferon (IFN-I) expression, but the underlying mechanisms are not yet understood. Here we reported that VP1, the capsid protein of CIAV, the major immunogenic protein that triggers the production of neutralizing antibodies in chickens, inhibited type I interferon (IFN-I) expression induced by cGAS-STING signaling. We showed that VP1 inhibited TBK1 phosphorylation and down stream signal transduction, leading to the inhibition of IFN-I expression. Subsequently, we demonstrated that VP1 interacted with TBK1. Finally, we clarified that aa 120-150 in VP1 was essential for VP1 to interact with TBK1 and inhibit cGAS-STING signaling. These findings will help us further understand the pathogenesis of CIAV in chickens.

The Use of Blended Teaching in Higher Medical Education during the Pandemic Era.

Objective: This study aims to compare the effect of blended teaching and traditional teaching in higher medical education during the pandemic era. Methods: Taking the teaching of neurology as an example, 293 Yangzhou University Clinical Medicine 2016 undergraduate students were selected as the research subjects, and were randomly divided into 2 groups a blended teaching group (n = 148) and a traditional teaching group (n = 145), and received blended teaching and traditional teaching, respectively. The blended teaching was based on a Massive Open Online Course, problem-based learning, and case-based learning and supplemented by Tencent video conferences, QQ messaging groups, and other auxiliary teaching tools. At the end of the course, the teaching effect and satisfaction rate were evaluated through theory assessment, practical skills assessment, and an anonymous questionnaire survey. Results: There were significant differences in theoretical achievements (81.83 ± 6.23 vs 76.79 ± 6.87, P < 0.001) and practical skill achievements (84.74 ± 6.50 vs 78.48 ± 6.53, P < 0.001). In addition, significant differences in all aspects of satisfaction rate were observed between the two groups (all P < 0.001). Conclusion: Blended teaching is beneficial to students' learning and stimulates their enthusiasm, cultivates clinical thinking ability, and improves teaching quality. Thus, it has played a positive role in the reform of higher medical teaching during the pandemic era.

Arrest of Cell Cycle by Avian Reovirus p17 through Its Interaction with Bub3.

Avian reoviruses (ARV) are a group of poultry pathogens that cause runting and stunting syndrome (RSS), a condition otherwise known as "frozen chicken", which are characterized by dramatically delayed growth in broilers. It has been known that p17, a nonstructural protein encoded by ARV, prohibits cellular proliferation by halting the cell cycle at the G2/M phase, the result of which is directly associated with the typical clinical sign of RSS. Nevertheless, the mechanism by which p17 modulates cell-cycle progression remains largely unknown. Here, we screened the interactome of ectopically expressed p17 through a yeast two-hybrid assay and identified Bub3, a cellular mitotic checkpoint protein, as a binding partner of p17. The infection of the Vero cells by ARV downregulated the Bub3 expression, while the knockdown of Bub3 alleviated the p17-modulated cell-cycle arrest during ARV infection. Remarkably, the suppression of Bub3 by RNAi in the Vero cells significantly reduced the viral mRNA and protein abundance, which eventually led to diminished virus replication. Altogether, our findings reveal that ARV p17 impedes host cell proliferation through a Bub3-dependent cell-cycle arrest, which eventually contributes to efficient virus replication. These results also unveil a hitherto unknown therapeutic target for RSS.

Host Combats IBDV Infection at Both Protein and RNA Levels.

Infectious bursal disease (IBD) is an acute, highly contagious, and immunosuppressive avian disease caused by infectious bursal disease virus (IBDV). In recent years, with the emergence of IBDV variants and recombinant strains, IBDV still threatens the poultry industry worldwide. It seems that the battle between host and IBDV will never end. Thus, it is urgent to develop a more comprehensive and effective strategy for the control of this disease. A better understanding of the mechanisms underlying virus-host interactions would be of help in the development of novel vaccines. Recently, much progress has been made in the understanding of the host response against IBDV infection. If the battle between host and IBDV at the protein level is considered the front line, at the RNA level, it can be taken as a hidden line. The host combats IBDV infection at both the front and hidden lines. Therefore, this review focuses on our current understanding of the host response to IBDV infection at both the protein and RNA levels.

Roles of RNA Sensors in Host Innate Response to Influenza Virus and Coronavirus Infections.

Influenza virus and coronavirus are two important respiratory viruses, which often cause serious respiratory diseases in humans and animals after infection. In recent years, highly pathogenic avian influenza virus (HPAIV) and SARS-CoV-2 have become major pathogens causing respiratory diseases in humans. Thus, an in-depth understanding of the relationship between viral infection and host innate immunity is particularly important to the stipulation of effective control strategies. As the first line of defense against pathogens infection, innate immunity not only acts as a natural physiological barrier, but also eliminates pathogens through the production of interferon (IFN), the formation of inflammasomes, and the production of pro-inflammatory cytokines. In this process, the recognition of viral pathogen-associated molecular patterns (PAMPs) by host pattern recognition receptors (PRRs) is the initiation and the most important part of the innate immune response. In this review, we summarize the roles of RNA sensors in the host innate immune response to influenza virus and coronavirus infections in different species, with a particular focus on innate immune recognition of viral nucleic acids in host cells, which will help to develop an effective strategy for the control of respiratory infectious diseases.

[Analysis of the structure of chicken Foxp3 and its expression profile in tissues].

In this study, we cloned the complete coding sequence (CDS) of chicken foxp3 (chfoxp3) gene, analyzed its structure, and investigated its expression profile in different chicken tissues. To be specific, chfoxp3 was cloned from the splenic tissue of 50-day-old specific-pathogen-free chickens, and analyzed by using online bioinformatics tools or software. The expression profiles of the chfoxp3 gene in different chicken tissues were detected by quantitative real-time PCR (qRT-PCR). The results indicated that the chfoxp3 gene contains an 882-bp open reading frame, encoding 293 amino acids hydrophilic protein with a molecular weight of 33.44 kDa. The chFoxp3 protein has a forkhead domain and carries a nuclear localization signal, which is typical in the Fox transcription factor family. The secondary structure of chFoxp3 consists of α-helix (29.35%), extended chain (10.92%), ß-turn (5.12%) and random coil (54.61%). The expression of chfoxp3 varied in different tissues. The expression levels of chfoxp3 in chicken heart and pancreas were higher than in spleen, bursa of Fabricius, thymus, and other immune organs (P < 0.01), which was quite different from that of mammals. Phylogenetic tree analysis showed that chFoxp3 belonged to the same clade as other wild birds did, but was far different from that of mammals. These results may facilitate further research on the role of chFoxp3 in immune regulation.

Gga-miR-30c-5p Suppresses Avian Reovirus (ARV) Replication by Inhibition of ARV-Induced Autophagy via Targeting ATG5.

Avian reovirus (ARV) causes viral arthritis, chronic respiratory diseases, retarded growth, and malabsorption syndrome. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression posttranscriptionally by silencing or degrading their targets, thus playing important roles in the host response to pathogenic infection. However, the role of miRNAs in host response to ARV infection is still not clear. In this study, we show that ARV infection markedly increased gga-miR-30c-5p expression in DF-1 cells and that transfection of cells with gga-miR-30c-5p inhibited ARV replication while knockdown of endogenous gga-miR-30c-5p enhanced viral growth in cells. Importantly, we identified the autophagy related 5 (ATG5), an important proautophagic protein, as a bona fide target of gga-miR-30c-5p. Transfection of DF-1 cells with gga-miR-30c-5p markedly reduced ATG5 expression accompanied with reduced conversion of ARV-induced-microtubule-associated protein 1 light chain 3 II (LC3-II) from LC3-I, an indicator of autophagy in host cell, while knockdown of endogenous gga-miR-30c-5p enhanced ATG5 expression as well as ARV-induced conversion of LC3-II, facilitating viral growth in cells. Furthermore, knockdown of ATG5 by RNA interference (RNAi) or treatment of cells with autophagy inhibitors (3-MA and wortmannin) markedly reduced ARV-induced LC3-II and syncytium formation, suppressing viral growth in cells, while overexpression of ATG5 increased ARV-induced LC3-II and syncytium formation, promoting viral growth in cells. Thus, gga-miR-30c-5p suppressed viral replication by inhibition of ARV-induced autophagy via targeting ATG5. These findings unraveled the mechanism of how host cells combat against ARV infection by self-encoded small RNA and furthered our understanding of the role of microRNAs in host response to pathogenic infection. IMPORTANCE Avian reovirus (ARV) is an important poultry pathogen causing viral arthritis, chronic respiratory diseases, and retarded growth, leading to considerable economic losses to the poultry industry across the globe. Elucidation of the pathogenesis of ARV infection is crucial to guiding the development of novel vaccines or drugs for the effective control of these diseases. Here, we investigated the role of miRNAs in host response to ARV infection. We found that infection of host cells by ARV remarkably upregulated gga-miR-30c-5p expression. Importantly, gga-miR-30c-5p suppressed ARV replication by inhibition of ARV-induced autophagy via targeting autophagy related 5 (ATG5) accompanied by suppression of virus-induced syncytium formation, thus serving as an important antivirus factor in host response against ARV infection. These findings will further our understanding of how host cells combat against ARV infection by self-encoded small RNAs and may be used as a potential target for intervening ARV infection.

Gga-miR-30c-5p Enhances Apoptosis in Fowl Adenovirus Serotype 4-Infected Leghorn Male Hepatocellular Cells and Facilitates Viral Replication through Myeloid Cell Leukemia-1.

Fowl adenovirus serotype 4 (FAdV-4) is the primary causative agent responsible for the hepatitis-hydropericardium syndrome (HHS) in chickens, leading to considerable economic losses to stakeholders. Although the pathogenesis of FAdV-4 infection has gained attention, the underlying molecular mechanism is still unknown. Here, we showed that the ectopic expression of gga-miR-30c-5p in leghorn male hepatocellular (LMH) cells enhanced apoptosis in FAdV-4-infected LMH cells by directly targeting the myeloid cell leukemia-1 (Mcl-1), facilitating viral replication. On the contrary, the inhibition of endogenous gga-miR-30c-5p markedly suppressed apoptosis and viral replication in LMH cells. Importantly, the overexpression of Mcl-1 inhibited gga-miR-30c-5p or FAdV-4-induced apoptosis in LMH cells, reducing FAdV-4 replication, while the knockdown of Mcl-1 by RNAi enhanced apoptosis in LMH cells. Furthermore, transfection of LMH cells with gga-miR-30c-5p mimics enhanced FAdV-4-induced apoptosis associated with increased cytochrome c release and caspase-3 activation. Thus, gga-miR-30c-5p enhances FAdV-4-induced apoptosis by directly targeting Mcl-1, a cellular anti-apoptotic protein, facilitating FAdV-4 replication in host cells. These findings could help to unravel the mechanism of how a host responds against FAdV-4 infection at an RNA level.

Advances on Innate Immune Evasion by Avian Immunosuppressive Viruses.

Innate immunity is not only the first line of host defense against pathogenic infection, but also the cornerstone of adaptive immune response. Upon pathogenic infection, pattern recognition receptors (PRRs) of host engage pathogen-associated molecular patterns (PAMPs) of pathogens, which initiates IFN production by activating interferon regulatory transcription factors (IRFs), nuclear factor-kappa B (NF-κB), and/or activating protein-1 (AP-1) signal transduction pathways in host cells. In order to replicate and survive, pathogens have evolved multiple strategies to evade host innate immune responses, including IFN-I signal transduction, autophagy, apoptosis, necrosis, inflammasome and/or metabolic pathways. Some avian viruses may not be highly pathogenic but they have evolved varied strategies to evade or suppress host immune response for survival, causing huge impacts on the poultry industry worldwide. In this review, we focus on the advances on innate immune evasion by several important avian immunosuppressive viruses (infectious bursal disease virus (IBDV), Marek's disease virus (MDV), avian leukosis virus (ALV), etc.), especially their evasion of PRRs-mediated signal transduction pathways (IFN-I signal transduction pathway) and IFNAR-JAK-STAT signal pathways. A comprehensive understanding of the mechanism by which avian viruses evade or suppress host immune responses will be of help to the development of novel vaccines and therapeutic reagents for the prevention and control of infectious diseases in chickens.

GATA3 Inhibits Viral Infection by Promoting MicroRNA-155 Expression.

Recognition of viral RNAs by melanoma differentiation associated gene-5 (MDA5) initiates chicken antiviral response by producing type I interferons. Our previous studies showed that chicken microRNA-155-5p (gga-miR-155-5p) enhanced IFN-ß expression and suppressed the replication of infectious burse disease virus (IBDV), a double-stranded RNA (dsRNA) virus causing infectious burse disease in chickens. However, the mechanism underlying IBDV-induced gga-miR-155-5p expression in host cells remains elusive. Here, we show that IBDV infection or poly(I:C) treatment of DF-1 cells markedly increased the expression of GATA-binding protein 3 (GATA3), a master regulator for TH2 cell differentiation, and that GATA3 promoted gga-miR-155-5p expression in IBDV-infected or poly(I:C)-treated cells by directly binding to its promoter. Surprisingly, ectopic expression of GATA3 significantly reduced IBDV replication in DF-1 cells, and this reduction could be completely abolished by treatment with gga-miR-155-5p inhibitors, whereas knockdown of GATA3 by RNA interference enhanced IBDV growth, and this enhancement could be blocked with gga-miR-155-5p mimics, indicating that GATA3 suppressed IBDV replication by gga-miR-155-5p. Furthermore, our data show that MDA5 is required for GATA3 expression in host cells with poly(I:C) treatment, so are the adaptor protein TBK1 and transcription factor IRF7, suggesting that induction of GATA3 expression in IBDV-infected cells relies on MDA5-TBK1-IRF7 signaling pathway. These results uncover a novel role for GATA3 as an antivirus transcription factor in innate immune response by promoting miR-155 expression, further our understandings of host response against pathogenic infection, and provide valuable clues to the development of antiviral reagents for public health. IMPORTANCE Gga-miR-155-5p acts as an important antivirus factor against IBDV infection, which causes a severe immunosuppressive disease in chicken. Elucidation of the mechanism regulating gga-miR-155-5p expression in IBDV-infected cells is essential to our understandings of the host response against pathogenic infection. This study shows that transcription factor GATA3 initiated gga-miR-155-5p expression in IBDV-infected cells by directly binding to its promoter, suppressing viral replication. Furthermore, induction of GATA3 expression was attributable to the recognition of dsRNA by MDA5, which initiates signal transduction via TBK1 and IRF7. Thus, it is clear that IBDV induces GATA3 expression via MDA5-TBK1-IRF7 signaling pathway, thereby suppressing IBDV replication by GATA3-mediated gga-miR-155-5p expression. This information remarkably expands our knowledge of the roles for GATA3 as an antivirus transcription factor in host innate immune response particularly at an RNA level and may prove valuable in the development of antiviral drugs for public health.

Gga-miR-29a-3p suppresses avian reovirus-induced apoptosis and viral replication via targeting Caspase-3.

Avian reovirus (ARV) is an important pathogen causing multiple types of clinical diseases in chickens, including viral arthritis, chronic respiratory diseases, retarded growth, and malabsorption syndrome, leading to considerable economic losses to the poultry industry across the globe. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression post transcriptionally by silencing or degrading their targets, thus playing important roles in the host response to pathogenic infection. However, the role of miRNAs in host response to ARV infection is still not clear. Here, we show that infection of DF-1 cells (a chicken fibroblast cell line) with ARV markedly altered the expressions of 583 chicken miRNAs(gga-miR), and that transfection of DF-1 cells with gga-miR-29a-3p, an upregulated miRNA in ARV-infected cells, significantly suppressed ARV-induced apoptosis via directly targeting Caspase-3, retarding ARV growth in cells. In contrast, knockdown of endogenous gga-miR-29a-3p in DF-1 cells by specific miRNA inhibitor enhanced ARV-induced apoptosis and increased the content and activity of caspase-3, facilitating viral growth in cells. Consistently, inhibition of Caspase-3 activity by inhibitors decreased viral titers in cell cultures. Thus, gga-miR-29a-3p plays an important antiviral role in host response to ARV infection by suppression of apoptosis via targeting Caspase-3. This information will further our understandings of how host cells combat against ARV infection by self-encoded small RNA and increase our knowledge of the role of microRNAs in host response to pathogenic infection.

The Evasion of Antiviral Innate Immunity by Chicken DNA Viruses.

The innate immune system constitutes the first line of host defense. Viruses have evolved multiple mechanisms to escape host immune surveillance, which has been explored extensively for human DNA viruses. There is growing evidence showing the interaction between avian DNA viruses and the host innate immune system. In this review, we will survey the present knowledge of chicken DNA viruses, then describe the functions of DNA sensors in avian innate immunity, and finally discuss recent progresses in chicken DNA virus evasion from host innate immune responses.