Viral regulation of host RNA degradation and its implication on hepatocarcinogenesis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07586
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49060:Virology-related
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Aly Hussein H 国立感染症研究所, ウイルス第二部, 主任研究官 (00523515)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: SKIV2L / HBV / RNA degradation

Outline of Final Research Achievements

We found that HBx protein significantly induced the expression of the RNA exosome co-factor (SKIV2L) suggesting that it may regulate the stability of other host /viral mRNA. Silencing of SKIV2L significantly enhanced the expression of OAS2. Hepatitis Delta Virus (HDV) is a satellite virus that depends on HBV. We found that SKIV2L significantly induced HDV replication. OAS2 played important role in this regulation. We hypothesized that HBx may increase cellular permissiveness to HDV infection by increasing SKIV2L levels and in turn suppressing OAS2 expression. We did not find any significant effect of HBx expression on OAS2 levels. We observed similar results by transfecting WT or a mutant HBV lacking the expression of HBx. From these results we concluded that there are no significant effect of SKIV2L on the HBx-mediated changes in cellular transcriptome. We also found that SKIV2L plays an important role in supporting HDV infection by suppressing host ISGs especially OAS2.

Free Research Field

Molecular Virolog

Academic Significance and Societal Importance of the Research Achievements

We found that the RNA exosome co-factor (SKIV2L) regulate Hepatitis Delta Virus (HDV) replication by the suppression of interferon stimulated gene (OAS2) expression.