Hepatitis E virus replication and interferon responses in human placental cells

Area of Science:

• Virology
• Hepatology
• Immunology

Background:

• Hepatitis E virus (HEV) causes significant mortality in pregnant women, particularly genotype 1 (gt1), while genotype 3 (gt3) infections are typically subclinical.
• The mechanisms underlying adverse maternal and fetal outcomes in HEV-infected pregnancies are not fully understood.

Purpose of the Study:

• To investigate the replication and behavior of HEV genotypes in placental-derived cells.
• To explore the differential responses of placental cells to HEV genotypes and antiviral treatments.
• To establish a cell-culture model for studying HEV pathogenesis during pregnancy and evaluating therapies.

Main Methods:

• HEV replication was assessed in JEG-3 placental cells following transfection.
• Viral capsid levels, infectivity, and biophysical properties were determined.
• Viral entry, inhibition by ribavirin and interferon-alpha, and host gene expression were analyzed.

Main Results:

• HEV completed its life cycle in JEG-3 cells, producing infectious particles similar to liver cells.
• Both HEV gt1 and gt3 were inhibited by ribavirin in placental cells.
• Placental cells showed lower sensitivity to interferon-alpha for gt1 HEV compared to liver cells, indicating genotype-specific host responses.

Conclusions:

• Differential tissue-specific host responses to HEV genotypes contribute to understanding severe outcomes in pregnancy.
• The developed placental cell-culture system is valuable for identifying and evaluating new therapeutic options for HEV infections during pregnancy.