Quantification of host proteomic responses to genotype 4 hepatitis E virus replication facilitated by pregnancy serum

Virol J. 2023 Jun 1;20(1):111. doi: 10.1186/s12985-023-02080-5.

Abstract

Background: Hepatitis E virus (HEV) infection is a common cause of acute hepatitis worldwide and causes approximately 30% case fatality rate among pregnant women. Pregnancy serum (PS), which contains a high concentration of estradiol, facilitates HEV replication in vitro through the suppression of the PI3K-AKT-mTOR and cAMPK-PKA-CREB signaling pathways. However, the proteomics of the complex host responses to HEV infection, especially how PS facilitates viral replication, remains unclear.

Methods: In this study, the differences in the proteomics of HEV-infected HepG2 cells supplemented with fetal bovine serum (FBS) from those of HEV-infected HepG2 cells supplemented with serum from women in their third trimester of pregnancy were quantified by using isobaric tags for relative and absolute quantification technology.

Results: A total of 1511 proteins were identified, among which 548 were defined as differentially expressed proteins (DEPs). HEV-infected cells supplemented with PS exhibited the most significant changes at the protein level. A total of 328 DEPs, including 66 up-regulated and 262 down-regulated proteins, were identified in HEV-infected cells supplemented with FBS, whereas 264 DEPs, including 201 up-regulated and 63 down-regulated proteins, were found in HEV-infected cells supplemented with PS. Subsequently, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that in HEV-infected cells, PS supplementation adjusted more host genes and signaling pathways than FBS supplementation. The DEPs involved in virus-host interaction participated in complex interactions, especially a large number of immune-related protein emerged in HEV-infected cells supplemented with PS. Three significant or interesting proteins, including filamin-A, thioredoxin, and cytochrome c, in HEV-infected cells were functionally verified.

Conclusions: The results of this study provide new and comprehensive insight for exploring virus-host interactions and will benefit future studies on the pathogenesis of HEV in pregnant women.

Keywords: Hepatitis E virus; Pregnancy; Proteomic analysis; Virus-host interactions; iTRAQ.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Female
  • Genotype
  • Hepatitis E virus* / genetics
  • Hepatitis E*
  • Humans
  • Phosphatidylinositol 3-Kinases / genetics
  • Pregnancy
  • Proteomics / methods
  • Virus Replication

Substances

  • Phosphatidylinositol 3-Kinases