Rab11a is required for porcine reproductive and respiratory syndrome virus induced autophagy to promote viral replication

et al. 2018

BMC Genet

Self Cite

BackgroundIn our previous genome-wide association study (GWAS) on the piglet splay leg (PSL) syndrome, the homer scaffolding protein 1 (HOMER1) was detected as a candidate gene. The aim of this work was to further verify the candidate gene by sequencing the gene and find the significantly associated mutation. Then we preliminarily analyzed the effect of the significant SNP on intronic promoter activity. This research provided a reference for further investigation of the pathogenesis of PSL.ResultWe investigated the 19 SNPs on HOMER1 and found 12 SNPs significant associated with PSL, including 8 SNPs resided in the potential intronic promoter region in intron 4. The − 663~ − 276 bp upstream the exon 5 had promoter activity and it could be an intronic promoter that regulated the transcription of HOMER1–205 transcript. The promoter activity of the − 663~ − 276 bp containing the rs339135425 and rs325197091 mutant alleles was significantly higher than of the wild type (P < 0.05). The G allele of rs325197091 (A > G) may create a new binding site of transcription factor aryl hydrocarbon receptor nuclear translocator (ARNT) and could enhance HOMER1 intronic promoter activity.ConclusionsHOMER1 gene was associated with the PSL, and the rs325197091 could influence HOMER1 intronic promoter activity in vitro.Electronic supplementary materialThe online version of this article (10.1186/s12863-018-0701-0) contains supplementary material, which is available to authorized users.

Section: Methodsmentioning

confidence: 99%

Polymorphisms of HOMER1 gene are associated with piglet splay leg syndrome and one significant SNP can affect its intronic promoter activity in vitro

Hao

et al. 2018

BMC Genet

Self Cite

“…Activation of the PI3K/AKT pathway leads to proliferation of B cells and activation of nuclear factor κ-light-chain-enhancer of activated B cells (NF-кB), triggering proin ammatory responses [47]. The endoplasmic reticulum is an organelle for viral replication and maturation, and a growing body of studies has shown that endoplasmic reticulum stress induces autophagy [48]. During viral production, infected cells synthesize large quantities of viral proteins and unfolded or misfolded proteins, which results in endoplasmic reticulum stress [48][49].…”

Section: Discussionmentioning

confidence: 99%

“…The endoplasmic reticulum is an organelle for viral replication and maturation, and a growing body of studies has shown that endoplasmic reticulum stress induces autophagy [48]. During viral production, infected cells synthesize large quantities of viral proteins and unfolded or misfolded proteins, which results in endoplasmic reticulum stress [48][49]. The aggregation of viral proteins in the endoplasmic reticulum is known as the unfolded protein response (UPR) [49].…”

Section: Discussionmentioning

confidence: 99%

Autophagy Inhibitors Treatment Alleviates Degree of Infection and Cerebral Inflammatory Responses in Mouse Model of Japanese Encephalitis

Han

Xie

et al. 2021

Preprint

Background: Japanese Encephalitis (JE) is a zoonotic natural epidemic disease caused by Japanese Encephalitis Virus (JEV) infection. Currently, there is no specific medicine for Japanese encephalitis. At present, autophagy regulating drugs have played an important role in the treatment of tumors, heart diseases and other diseases. We hope that by studying the effects of autophagy-regulating drugs on JEV infection and host response in mice, will provide effective clinical trials for autophagy-regulating drugs in the treatment of Japanese encephalitis and other viral infectious diseases. Methods: After establishing appropriate animal model. We observed the neurological symptoms of the mice and counted their survival rate. We compared the degree of viral infection in the brain of mice infected with JE virus. We compared the extent of neuroinflammatory responses in the brain of mice and explored the signaling processes involved in neuroinflammation.Results: We found autophagy inhibitors wortmannin (Wort) and chloroquine (CQ) alleviate degree of viral infection in the brain of JEV-infected mice. Autophagy inhibitors reduced the neuroinflammation in Mouse Model of Japanese encephalitis. We speculated that autophagy inhibitors may attenuate the activation of the PI3K/AKT/NF-kB pathway, thereby reducing the brain inflammation in mice, thereby protecting mice from JEV-induced death. This result is not significant enough, the specific mechanism still needs further study.Conclusions: Our study suggests that autophagy inhibitors wortmannin and chloroquine could reduce the degree of viral infection and inflammatory response in the brain of JEV infected mice, providing a clinical basis for the treatment of Japanese encephalitis.

“…Activation of the PI3K/AKT pathway leads to proliferation of B cells and activation of nuclear factor κlight-chain-enhancer of activated B cells (NF-кB), triggering proin ammatory responses [42]. The endoplasmic reticulum is an organelle for viral replication and maturation, and a growing body of studies has shown that endoplasmic reticulum stress induces autophagy [43]. During viral production, infected cells synthesize large quantities of viral proteins and unfolded or misfolded proteins, which results in endoplasmic reticulum stress [43][44].…”

Section: Discussionmentioning

confidence: 99%

“…The endoplasmic reticulum is an organelle for viral replication and maturation, and a growing body of studies has shown that endoplasmic reticulum stress induces autophagy [43]. During viral production, infected cells synthesize large quantities of viral proteins and unfolded or misfolded proteins, which results in endoplasmic reticulum stress [43][44]. The aggregation of viral proteins in the endoplasmic reticulum is known as the unfolded protein response (UPR) [44].…”

Section: Discussionmentioning

confidence: 99%

Autophagy inhibitor treatment alleviates cerebral inflammatory responses in a mouse model of Japanese encephalitis

Han

Xie

et al. 2020

Preprint

Background Japanese Encephalitis (JE) is a zoonotic natural epidemic disease caused by Japanese Encephalitis Virus (JEV) infection. Currently, there is no specific medicine for Japanese encephalitis. Autophagy is a lysosomal degradation process that plays an important role in viral infection and cellular immunity. In vitro studies have shown that the Japanese encephalitis virus replication mechanism is related to the autophagy pathway. We hope that by studying the effects of autophagy-regulating drugs on JEV infection and host response in mice, will provide effective clinical trials for autophagy-regulating drugs in the treatment of Japanese encephalitis and other viral infectious diseases. Methods After establishing appropriate animal model. We observed the neurological symptoms of the mice and counted their survival rate. We observed histopathological changes in brain tissues of mice. We compared the extent of neuroinflammatory responses in the brain of mice and explored the signaling processes involved in neuroinflammation. Results We found autophagy inhibitors wortmannin (Wort) and chloroquine (CQ) slow down the occurrence of neurological symptoms and reduce the prevalence of JEV-infected mice. As expected, autophagy inhibitors can inhibit the activation of the PI3K/AKT/NF-kB pathway to alleviate cerebral inflammatory responses in mice, thereby protecting the mice from JEV-induced death. Conclusions Our study suggests that autophagy inhibitors wortmannin and chloroquine could attenuate the inflammatory response in the brain of JEV infected mice, providing a clinical basis for the treatment of Japanese encephalitis