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CXCL10 is produced in hepatitis A virus-infected cells in an IRF3-dependent but IFN-independent manner.

ABSTRACT: Acute hepatitis A caused by hepatitis A virus (HAV) infection is accompanied by severe liver injury in adult patients, and the liver injury is associated with the production of chemokines. Herein, we investigated the mechanism of how HAV infection induces the production of CXCR3 and CCR5 chemokines, such as CXCL10, CCL4 and CCL5. The production of CXCL10, CCL4 and CCL5 was markedly increased by HAV (HM-175/18f) infection in the culture of primary human hepatocytes and HepG2 cells. In particular, CXCL10 was produced in HAV-infected cells, not in neighboring uninfected cells. Moreover, these chemokines were significantly increased in the sera of acute hepatitis A patients. The production of IFN-?s was also robustly induced by HAV infection, and the blocking of secreted IFN-?s partially abrogated the production of CCL4 and CCL5 in HAV-infected cells. However, CXCL10 production was not decreased by the blocking of IFN-?s. Instead, CXCL10 production was reduced by silencing the expression of RIG-I-like receptor (RLR) signal molecules, such as mitochondrial antiviral signaling protein and interferon regulatory factor 3, in HAV-infected cells. In conclusion, HAV infection strongly induces the production of helper 1 T cell-associated chemokines, particularly CXCL10 via RLR signaling, even without secreted IFNs.

SUBMITTER: Sung PS

PROVIDER: S-EPMC5527116 | biostudies-other | 2017 Jul

REPOSITORIES: biostudies-other

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CXCL10 is produced in hepatitis A virus-infected cells in an IRF3-dependent but IFN-independent manner.

Sung Pil Soo PS Hong Seon-Hui SH Lee Jeewon J Park Su-Hyung SH Yoon Seung Kew SK Chung Woo Jin WJ Shin Eui-Cheol EC

Scientific reports 20170725 1

Acute hepatitis A caused by hepatitis A virus (HAV) infection is accompanied by severe liver injury in adult patients, and the liver injury is associated with the production of chemokines. Herein, we investigated the mechanism of how HAV infection induces the production of CXCR3 and CCR5 chemokines, such as CXCL10, CCL4 and CCL5. The production of CXCL10, CCL4 and CCL5 was markedly increased by HAV (HM-175/18f) infection in the culture of primary human hepatocytes and HepG2 cells. In particular, ...[more]

PMID: 28744018

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Dataset Information

CXCL10 is produced in hepatitis A virus-infected cells in an IRF3-dependent but IFN-independent manner.

Publications

CXCL10 is produced in hepatitis A virus-infected cells in an IRF3-dependent but IFN-independent manner.

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