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

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.

Multi-epitope vaccine design for hepatitis E virus based on protein ORF2 and ORF3

“…Hepatitis E is a self-limiting disease, but presents a serious threat to pregnant women and immunocompromised individuals ( Qian et al, 2023 ). There is no global vaccine currently available against HEV.…”

“…It is self-limiting or asymptomatic in healthy individuals, but causes high mortality in immunocompromised patients, such as pregnant women. The case fatality rate in pregnant women is up to 30% ( Qian et al, 2023 ). There are eight genotypes of Orthohepevirus A species in the Hepeviridae family, of which four genotypes infect humans ( Marion et al, 2020 ).…”