Influenza control strategies rely on annual immunization and require frequent updates of the vaccine, which is not always a foolproof process. Furthermore, current antivirals are also losing effectiveness as new viral strains often refractory to conventional treatments. Thus, there an urgent need find antiviral mechanisms develop therapeutic drugs based these mechanisms. Targeting virus-host interface emerging strategy because host factors controlling replication activity will be ideal...

Summary Neurologic dysfunctions such as Guillain–Barre′ syndrome, encephalitis, meningitis and transverse myelitis occur frequently in patients with hepatitis E virus ( HEV ) infection, this study was conducted to better characterize the role of pathogenesis neurologic disorders. Genotype 4 strain swine used inoculate Mongolian gerbils. Reverse transcription–nested polymerase chain reaction RT ‐ nPCR ), ELISA , histopathology, ultrastructural pathology enzyme immunohistochemistry method were...

Extrahepatic injury, particularly neurologic dydfunctions such as Guillain-Barré syndrome, amyotrophy, and encephalitis/meningoencephalitis /myositis were associated with HEV infection, which was supported by both clinical laboratory studies. Thus, it is crucial to figure out how the virus invades into central nervous system. In this study, system lesions determined in rabbits Mongolian gerbils inoculated genotype 4 HEV. Junctional proteins detected infected primary human brain microvascular...

The DNA sensor cGAS detects cytosolic and instigates type I interferon (IFN) expression. Recent studies find that also localizes in the nucleus binds chromatin. Despite mechanism controlling nuclear activation is well elucidated, whether participates sensing unclear. Here, we report herpes simplex virus 1 (HSV-1) infection caused release of from chromatin into soluble fraction. Like its counterpart, leaked sensed viral DNA, produced cGAMP, induced mRNA expression IFN interferon-stimulated...

Abstract NF-κB signaling regulates diverse processes such as cell death, inflammation, immunity, and cancer. The activity of is controlled by methionine 1-linked linear polyubiquitin, which assembled the ubiquitin chain assembly complex (LUBAC) ubiquitin-conjugating enzyme UBE2L3. Recent studies found that deubiquitinase OTULIN breaks chain, thus inhibiting signaling. Despite essential role in has been established, regulatory mechanism for not well elucidated. To discover potential...

Hepatitis E virus (HEV) infection has been associated with a wide range of extrahepatic manifestations, so this study was designed to examine the effect and role HEV on structural molecular changes in testicular tissues Mongolian gerbils experimentally infected swine HEV. RNA first detected testis at 14 days post-inoculation reached peak between 28 42 later viral load 3.12 6.23 logs/g by PCR assays. Changes including vacuolation, sloughing germ cells, formation multinuclear giant...

Hepatitis E virus (HEV) infection has been associated with extrahepatic manifestations, particularly neurological disorders. Although it reported that HEV induced hepatocyte apoptosis mitochondria injury, activation of mitochondrial apoptotic pathway in the central nervous system during was not clearly understood. In this study, induction apoptosis-associated proteins and pro-inflammatory cytokines were detected infected Mongolian gerbil model primary human brain microvascular endothelial...

Vesicular stomatitis virus (VSV) is a zoonotic, negative-stranded RNA of the family Rhabdoviridae. The nucleoprotein (N) VSV protects viral genomic and plays an essential role in transcription replication, which makes ideal target host defense. However, whether how innate/intrinsic immunity limits infection by targeting N protein are unknown. In this study, we found that (VSV-N) interacted with ubiquitin E3 ligase, tripartite motif 41 (TRIM41). Overexpression TRIM41 inhibited infection....

Increasing evidence demonstrates that hepatitis E virus (HEV) can be transmitted across species. According to previous reports, swine HEV has two genotypes, genotype 3 and 4, both infect humans by the fecal-oral route. Thus, it is crucial for control of zoonotic transmission evaluate dynamics viral shedding distribution in different tissues during cross-species infection HEV. In this study, rabbits were infected with 4 intraperitoneal The results showed RNA not only shed feces but also...

Influenza A virus (IAV) is a highly transmissible respiratory pathogen and constant threat to global health with considerable economic social impact. viral RNA sensed by host pattern recognition receptors (PRRs), such as the Toll-like receptor 7 (TLR7) retinoic acid-inducible gene I (RIG-I). The activation of these PRRs instigates interferon regulatory factor (IRF) nuclear kappa B (NF-κB) signaling pathways that induce expression interferon-stimulated genes (ISGs) inflammatory genes....

Epidermal growth factor receptor (EGFR) is a tyrosine kinase that instigates several signaling cascades, including the NF-κB pathway, to induce cell differentiation and proliferation. Overexpression mutations of EGFR are found in up 30% solid tumors correlate with poor prognosis. Although it known EGFR-mediated activation involved tumor development, axis not well elucidated. Here, we plakophilin 2 (PKP2) linear ubiquitin chain assembly complex (LUBAC) were required for activation. Upon EGF...

Human coronaviruses exhibit a spectrum of symptoms, ranging from mild seasonal colds to severe respiratory manifestations. Despite progress in understanding the host's innate defense mechanisms against coronaviruses, how these viruses manipulate immune response promote inflammation remains elusive. In this study, we unveil role coronavirus nonstructural protein 14 (NSP14) leveraging linear ubiquitin chain assembly complex (LUBAC) instigate NF-κB activation, thereby triggering proinflammatory...

The aim of this study was to investigate the occurrence hepatitis E virus (HEV) in sewage samples Shen Zhen, China. Sewage were collected from 152 plants including livestock sewage, domestic and treated May July 2015. Two HEV positive (1.32%) plants. Partial ORF2 fragments sequenced a phylogenetic tree constructed using MEGA5.1. Blast analyses showed that both these two sequences belonged Genotype 4. To best our knowledge, is first on molecular characterization wastewater China time detect 4...

Hepatitis E virus (HEV) infection can induce infertility and miscarriage in pregnant women infect neonates through vertical transmission. However, the mechanism of transmission remains unclear. In present study, we evaluated replication HEV ovary structural molecular changes induced by after intraperitoneal injection rabbits. Positive- negative-strand RNA was detected ovaries at 28 49 days post-infection. Positive open reading frames 2 3 signals were observed immunohistochemistry staining....

Abstract Retinoic acid-inducible gene I (RIG-I) senses viral RNA and instigates an innate immune signaling cascade to induce type interferon expression. Currently, the regulatory mechanisms controlling RIG-I activation remain be fully elucidated. Here we show that FAK family kinase-interacting protein of 200 kDa (FIP200) facilitates activation. FIP200 deficiency impaired increased host susceptibility virus infection. In vivo studies further demonstrated knockout mice were more susceptible...

Human Cytomegalovirus (HCMV) infections can be found throughout the body, especially in epithelial tissue. Animal model was established by inoculation of HCMV (strain AD-169) or coinoculation with Hepatitis E virus (HEV) into ligated sacculus rotundus and vermiform appendix living rabbits. The specimens were collected from animals sacrificed 1 a half hours after infection.The to capable reproducing these through RT-PCR Western-blot. Severe inflammation damage HCMV-infected viral protein...

Abstract Stimulator of interferon genes (STING) is an endoplasmic reticulum (ER) protein that plays a crucial role in cytosolic DNA‐mediated innate immunity. Both STING agonists and antagonists have demonstrated their ability to enhance mouse survival against coronavirus, however, the physiological endogenous coronavirus infection remains unclear. Our research unveils inhibits replication by impeding formation ER‐derived double‐membrane vesicles (DMVs), organelles which replicates. We found...

Abstract Retinoic acid-inducible gene I (RIG-I) is a cytosolic sensor for recognition of viral double-stranded RNA (dsRNA) and 5′ triphosphate RNA, which induces robust production type interferon (IFN). Following recognition, the caspase activation recruitment domain (CARD) RIG-I released from repressor subsequently oligomerized to activate downstream signal cascades. Although these sequential steps are well established; however, regulatory mechanism not elucidated. In this study, we found...

Abstract Epidermal growth factor receptor (EGFR) is a tyrosine kinase that instigates several signaling cascades, including NF-κB pathway, to induce cell differentiation and proliferation. Overexpression mutations of EGFR are found in up 30% solid tumors correlate with poor prognosis. Although it known EGFR-mediated activation involved tumor development, the axis not well elucidated. Here, we plakophilin 2 (PKP2) linear ubiquitin chain assembly complex (LUBAC) were required for activation....