Hepatitis E Virus Persistence and/or Replication in the Peripheral Blood Mononuclear Cells of Acute HEV-Infected Patients

Ibrahim M Sayed; Zeinab A Abd Elhameed; Doaa M Abd El-Kareem; Mohamed A Y Abdel-Malek; Mohamed E Ali; Maggie A Ibrahim; Ayat Abdel-Rahman Sayed; Khaled Abo Bakr Khalaf; Lobna Abdel-Wahid; Mohamed A El-Mokhtar

doi:10.3389/fmicb.2021.696680

Hepatitis E Virus Persistence and/or Replication in the Peripheral Blood Mononuclear Cells of Acute HEV-Infected Patients

Front Microbiol. 2021 Jul 16:12:696680. doi: 10.3389/fmicb.2021.696680. eCollection 2021.

Affiliations

¹ Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt.
² Department of Pathology, School of Medicine, University of California, San Diego, La Jolla, CA, United States.
³ Department of Clinical Pathology, Faculty of Medicine Assiut University, Assiut, Egypt.
⁴ Department of Microbiology and Immunology, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt.
⁵ Department of Medical Biochemistry, Faculty of Medicine, Assiut University, Assiut, Egypt.
⁶ Department of Tropical Medicine and Gastroenterology, Faculty of Medicine, Assiut University, Assiut, Egypt.
⁷ Gastroenterology and Hepatology Unit, Department of Internal Medicine, Faculty of Medicine, Assiut University, Assiut, Egypt.
⁸ Microbiology and Immunology Department, Faculty of Pharmacy, Sphinx University, Assiut, Egypt.

Abstract

Background: Hepatitis E virus (HEV) causes about 14 million infections with 300,000 deaths and 5,200 stillbirths worldwide annually. Extrahepatic manifestations are reported with HEV infections, such as renal, neurological, and hematological disorders. Recently, we reported that stool-derived HEV-1 replicates efficiently in human monocytes and macrophages in vitro. However, another study reports the presence of viral RNA but no evidence of replication in the PBMCs of acute hepatitis E (AHE) patients. Therefore, the replication of HEV in PBMCs during AHE infection is not completely understood.

Methods: PBMCs were isolated from AHE patients (n = 17) enrolled in Assiut University Hospitals, Egypt. The viral load, positive (+) and negative (-) HEV RNA strands and viral protein were assessed. The gene expression profile of PBMCs from AHE patients was assessed. In addition, the level of cytokines was measured in the plasma of the patients.

Results: HEV RNA was detected in the PBMCs of AHE patients. The median HEV load in the PBMCs was 1.34 × 10³ IU/ml. A negative HEV RNA strand and HEV open reading frame 2 protein were recorded in 4/17 (23.5%) of the PBMCs. Upregulation of inflammatory transcripts and increased plasma cytokines were recorded in the AHE patients compared with healthy individuals with significantly elevated transcripts and plasma cytokines in the AHE with detectable (+) and (-) RNA strands compared with the AHE with the detectable (+) RNA strand only. There was no significant difference in terms of age, sex, and liver function tests between AHE patients with detectable (+) and (-) RNA strands in the PBMCs and AHE patients with the (+) RNA strand only.

Conclusion: Our study shows evidence for in vivo HEV persistence and replication in the PBMCs of AHE patients. The replication of HEV in the PBMCs was associated with an enhanced immune response, which could affect the pathogenesis of HEV.

Keywords: HEV; PBMCs; acute hepatitis; cytokines; gene expression; persistence and replication.