scholarly journals RNA Helicase DDX3 Interacts with the Capsid Protein of Hepatitis E Virus and Plays an Indispensable Role in the Viral Replication

2020 ◽  
Author(s):  
Shaoli Lin ◽  
Peixi Chang ◽  
Jia He ◽  
Etienne Coyaud ◽  
Brian Pierce ◽  
...  
Keyword(s):  
Viral Replication ◽  
Capsid Protein ◽  
Hepatitis E Virus ◽  
Direct Interaction ◽  
Hepatitis E ◽  
Rna Helicase ◽  
Type I Interferons ◽  
Type I ◽  
Interferon Induction

DDX3 is an ATP-dependent RNA helicase involved in multiple cellular activities, including RNA metabolism and innate immunity. DDX3 is known to assist the replication of some viruses while restricting some others through direct interaction with the viral proteins. However, the role of DDX3 in the replication of the hepatitis E virus (HEV) is unknown. In this study, DDX3 is shown to interact with the HEV capsid protein and provide an indispensable role in HEV replication. The DDX3 C-terminal domain was demonstrated to interact with the capsid protein, which was previously demonstrated to inhibit the production of type I interferons. Knockdown of DDX3 compromised the capsid protein-mediated blockage of interferon induction. Notably, DDX3 silencing led to a significant reduction in HEV replication. Also, the ATPase activity of DDX3 is required for the HEV replication as an ATPase-null mutant DDX3 failed to rescue the viral replication in the DDX3-silenced cells. These results demonstrate a pro-viral role of DDX3 in HEV replication, providing further insights into the virus-cell interactions.

Role of hepatitis E virus antigen in confirming active viral replication in patients with acute viral hepatitis E infection

2013 ◽  
Vol 58 (2) ◽  
pp. 374-377 ◽  
Author(s):  
Ekta Gupta ◽  
Priyanka Pandey ◽  
Shivani Pandey ◽  
Manoj Kumar Sharma ◽  
Shiv Kumar Sarin
Keyword(s):  
Viral Replication ◽  
Viral Hepatitis ◽  
Hepatitis E Virus ◽  
Acute Viral Hepatitis ◽  
Hepatitis E ◽  
Virus Antigen ◽  
Active Viral Replication

scholarly journals Hepatitis E Virus Methyltransferase Inhibits Type I Interferon Induction by Targeting RIG-I

2018 ◽  
Vol 28 (9) ◽  
pp. 1554-1562 ◽  
Author(s):  
Sangmin Kang ◽  
Changsun Choi ◽  
Insoo Choi ◽  
Guinam Han ◽  
Seong Woon Rho ◽  
...  
Keyword(s):  
Hepatitis E Virus ◽  
Type I Interferon ◽  
Hepatitis E ◽  
Type I ◽  
Interferon Induction

Role of asparagine at position 562 in dimerization and immunogenicity of the hepatitis E virus capsid protein

2016 ◽  
Vol 37 ◽  
pp. 99-107 ◽  
Author(s):  
Mingjie Xu ◽  
Nouredine Behloul ◽  
Jiyue Wen ◽  
Jianhua Zhang ◽  
Jihong Meng
Keyword(s):  
Capsid Protein ◽  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Virus Capsid ◽  
Virus Capsid Protein

scholarly journals An essential RNA element resides in a central region of hepatitis E virus ORF2

2013 ◽  
Vol 94 (7) ◽  
pp. 1468-1476 ◽  
Author(s):  
Suzanne U. Emerson ◽  
Hanh T. Nguyen ◽  
Udana Torian ◽  
Karly Mather ◽  
Andrew E. Firth
Keyword(s):  
Capsid Protein ◽  
Central Region ◽  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Luciferase Expression ◽  
Stem Loop ◽  
Subgenomic Rna ◽  
Compensatory Mutations ◽  
Precise Role

Hepatitis E virus (genus Hepevirus, family Hepeviridae) is one of the most important causes of acute hepatitis in adults, particularly among pregnant women, throughout Asia and Africa where mortality rates can be 20–30 %. Hepatitis E virus has a single-stranded positive-sense RNA genome that contains three translated ORFs. The two 3′ ORFs are translated from a subgenomic RNA. Functional RNA elements have been identified in and adjacent to the genomic 5′ and 3′ UTRs and in and around the intergenic region. Here we describe an additional RNA element that is located in a central region of ORF2. The RNA element is predicted to fold into two highly conserved stem–loop structures, ISL1 and ISL2. Mutations that disrupt the predicted structures, without altering the encoded amino acid sequence, result in a drastic reduction in capsid protein synthesis. This indicates that the RNA element plays an important role in one of the early steps of virus replication. The structures were further investigated using a replicon that expresses Gaussia luciferase in place of the capsid protein. Single mutations in ISL2 severely reduced luciferase expression, but a pair of compensatory mutations that were predicted to restore the ISL2 structure, restored luciferase expression to near-WT levels, thus lending experimental support to the predicted structure. Nonetheless the precise role of the ISL1+ISL2 element remains unknown.

scholarly journals TBK1 recruitment to STING mediates autoinflammatory arthritis caused by defective DNA clearance

2021 ◽  
Vol 219 (1) ◽  
Author(s):  
Tong Li ◽  
Seoyun Yum ◽  
Minghao Li ◽  
Xiang Chen ◽  
Xiaoxia Zuo ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Therapeutic Strategy ◽  
Inflammatory Diseases ◽  
Type I Interferons ◽  
Type I ◽  
Disease Manifestation ◽  
Dnase Ii ◽  
Interferon Induction ◽  
Tnf Α

Defective DNA clearance in DNase II−/− mice leads to lethal inflammatory diseases that can be rescued by deleting cGAS or STING, but the role of distinct signaling pathways downstream of STING in the disease manifestation is not known. We found that the STING S365A mutation, which abrogates IRF3 binding and type I interferon induction, rescued the embryonic lethality of DNase II−/− mice. However, the STING S365A mutant retains the ability to recruit TBK1 and activate NF-κB, and DNase II−/−STING-S365A mice exhibited severe polyarthritis, which was alleviated by neutralizing antibodies against TNF-α or IL-6 receptor. In contrast, the STING L373A mutation or C-terminal tail truncation, which disrupts TBK1 binding and therefore prevents activation of both IRF3 and NF-κB, completely rescued the phenotypes of DNase II−/− mice. These results demonstrate that TBK1 recruitment to STING mediates autoinflammatory arthritis independently of type I interferons. Inhibiting TBK1 binding to STING may be a therapeutic strategy for certain autoinflammatory diseases instigated by self-DNA.

Hepatitis E virus‐encoded microRNA promotes viral replication by inhibiting type I interferon

2021 ◽  
Vol 36 (1) ◽  
Author(s):  
Zhongyao Qian ◽  
Chenchen Yang ◽  
Liangheng Xu ◽  
Houfack K. Mickael ◽  
Shuangfeng Chen ◽  
...  
Keyword(s):  
Viral Replication ◽  
Hepatitis E Virus ◽  
Type I Interferon ◽  
Hepatitis E ◽  
Type I

scholarly journals Hepatitis E Virus Inhibits Type I Interferon Induction by ORF1 Products

2014 ◽  
Vol 88 (20) ◽  
pp. 11924-11932 ◽  
Author(s):  
Y. Nan ◽  
Y. Yu ◽  
Z. Ma ◽  
S. K. Khattar ◽  
B. Fredericksen ◽  
...  
Keyword(s):  
Hepatitis E Virus ◽  
Type I Interferon ◽  
Hepatitis E ◽  
Type I ◽  
Interferon Induction

The Role of Toll-Like Receptors and Type I Interferons in Host Responses to Bacteria

2009 ◽  
Vol 5 (2) ◽  
pp. 143-149
Author(s):  
Marja Ojaniemi ◽  
Mari Liljeroos ◽  
Reetta Vuolteenaho
Keyword(s):  
Type I Interferons ◽  
Host Responses ◽  
Type I ◽  
Toll Like Receptors

scholarly journals Hepatitis E and Pregnancy: An Unholy Alliance Unmasked from Kashmir, India

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1329
Author(s):  
Mohammad Sultan Khuroo
Keyword(s):  
Viral Replication ◽  
Pregnant Women ◽  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Polymerase Activity ◽  
Severe Liver ◽  
Reading Frame ◽  
Multiple Factors ◽  
Severe Liver Disease ◽  
Development And Management

The adverse relationship between viral hepatitis and pregnancy in developing countries had been interpreted as a reflection of retrospectively biased hospital-based data collection by the West. However, the discovery of hepatitis E virus (HEV) as the etiological agent of an epidemic of non-A, non-B hepatitis in Kashmir, and the documenting of the increased incidence and severity of hepatitis E in pregnancy via a house-to-house survey, unmasked this unholy alliance. In the Hepeviridae family, HEV-genotype (gt)1 from genus Orthohepevirus A has a unique open reading frame (ORF)4-encoded protein which enhances viral polymerase activity and viral replication. The epidemics caused by HEV-gt1, but not any other Orthohepevirus A genotype, show an adverse relationship with pregnancy in humans. The pathogenesis of the association is complex and at present not well understood. Possibly multiple factors play a role in causing severe liver disease in the pregnant women including infection and damage to the maternal-fetal interface by HEV-gt1; vertical transmission of HEV to fetus causing severe fetal/neonatal hepatitis; and combined viral and hormone related immune dysfunction of diverse nature in the pregnant women, promoting viral replication. Management is multidisciplinary and needs a close watch for the development and management of acute liver failure. (ALF). Preliminary data suggest beneficial maternal outcomes by early termination of pregnancy in patients with lower grades of encephalopathy.

Sign in / Sign up

Export Citation Format

Share Document