Background
eIF2α is a regulatory node that controls protein synthesis initiation by its phosphorylation or dephosphorylation. General control nonderepressible-2 (GCN2), protein kinase R-like endoplasmic reticulum kinase (PERK), double-stranded RNA (dsRNA)-dependent protein kinase (PKR) and heme-regulated inhibitor (HRI) are four kinases that regulate eIF2α phosphorylation.
Main body
In the viral infection process, dsRNA or viral proteins produced by viral proliferation activate different eIF2α kinases, resulting in eIF2α phosphorylation, which hinders ternary tRNAMet-GTP-eIF2 complex formation and inhibits host or viral protein synthesis. The stalled messenger ribonucleoprotein (mRNP) complex aggregates under viral infection stress to form stress granules (SGs), which encapsulate viral RNA and transcription- and translation-related proteins, thereby limiting virus proliferation. However, many viruses have evolved a corresponding escape mechanism to synthesize their own proteins in the event of host protein synthesis shutdown and SG formation caused by eIF2α phosphorylation, and viruses can block the cell replication cycle through the PERK-eIF2α pathway, providing a favorable environment for their own replication. Subsequently, viruses can induce host cell autophagy or apoptosis through the eIF2α-ATF4-CHOP pathway.
Conclusions
This review summarizes the role of eIF2α in viral infection to provide a reference for studying the interactions between viruses and hosts.
Tibial dyschodroplasia (TD) is a most common pathological condition in many avian species that is characterized by failure of growth plate (GP) modeling that leads to the persistence of avascular lesion in the GP. Tetramethylpyrazine (TMP) is widely used to treat neurovascular disorders and pulmonary hypertension, but no report is available about promoting effect of TMP against TD. Therefore, a total of 210 broiler chicks were equally divided into three groups; Control, TD and TMP. During the experiment mortality rate, chicken performance indicators (daily weight, average daily feed intake, average daily weight gain and feed conversion ratio), tibia bone indicators (weight, length, width of tibial and the size of GP) in addition to gene expression of HIF-1α and VEGF were examined. The results showed that TMP administration restore the GP width, increase growth performance, and mitigated the lameness in broiler chickens. The expression of HIF-1α and VEGF increased significantly in TD affected thiram induced chicks. Whereas, TMP treatment down-regulated HIF-1α and VEGF genes and proteins expressions. The present study demonstrates that the TMP plays an important role in angiogenesis during the impairment and recovery of GP in TD via regulation of the HIF-1α/VEGF signaling pathway in chickens.
Alphaherpesviruses are a large family of highly successful human and animal DNA viruses that can establish lifelong latent infection in neurons. All alphaherpesviruses have a protein-rich layer called the tegument that, connects the DNA-containing capsid to the envelope. Tegument proteins have a variety of functions, playing roles in viral entry, secondary envelopment, viral capsid nuclear transportation during infection, and immune evasion. Recently, many studies have made substantial breakthroughs in characterizing the innate immune evasion of tegument proteins. A wide range of antiviral tegument protein factors that control incoming infectious pathogens are induced by the type I interferon (IFN) signaling pathway and other innate immune responses. In this review, we discuss the immune evasion of tegument proteins with a focus on herpes simplex virus type I.
Tibial dyschondroplasia (TD) is the most-prevalent leg disorder in fast-growing chickens; it is intractable and characterized by abnormal endochondral bone formation of proximal tibial growth-plates (TGPs). Previous studies have shown that bone is a highly vascularized tissue dependent on the coordinated coupling between angiogenesis and osteogenesis, but the underlying mechanisms of bone formation and bone remodeling are poorly defined in TD chickens. Here, we observed that inhibition of vasculogenesis and angiogenesis remarkably impaired vascular invasion in the hypertrophic chondrocyte zone of the TGPs, resulting in the massive death of chondrocytes due to a shortage of blood vessels and nutrients. Moreover, the balance of the OPG (osteoprotegerin)/RANKL (receptor activator of nuclear factor-kB ligand) system is also severely disrupted during the osteogenesis process while coupling with angiogenesis, both of which eventually lead to abnormal endochondral bone formation in TD chickens. Thus, the process of vascular formation in endochondral bone appears to initiate the pathological changes in TD, and improvement of this process during coupling with osteogenesis may be a potential therapeutic approach to treat this intractable disease.
Tibial dyschondroplasia (TD) is one of the most common problems in the poultry industry and leads to lameness by affecting the proximal growth plate of the tibia. However, due to the unique environmental and geographical conditions of Tibet, no case of TD has been reported in Tibetan chickens (TBCs). The present study was designed to investigate the effect of high altitude hypoxia on blood parameters and tibial growth plate development in chickens using the complete blood count, morphology, and histological examination. The results of this study showed an undesirable impact on the overall performance, body weight, and mortality of Arbor Acres chickens (AACs) exposed to a high altitude hypoxic environment. However, AACs raised under hypoxic conditions showed an elevated number of red blood cells (RBCs) and an increase in hemoglobin and hematocrit values on day 14 compared to the hypobaric normoxia group. Notably, the morphology and histology analyses showed that the size of tibial growth plates in AACs was enlarged and that the blood vessel density was also higher after exposure to the hypoxic environment for 14 days, while no such change was observed in TBCs. Altogether, our results revealed that the hypoxic environment has a potentially new role in increasing the blood vessel density of proximal tibial growth plates to strengthen and enhance the size of the growth plates, which may provide new insights for the therapeutic manipulation of hypoxia in poultry TD.
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