PMID- 32455708
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2076-393X (Print)
IS  - 2076-393X (Electronic)
IS  - 2076-393X (Linking)
VI  - 8
IP  - 2
DP  - 2020 May 21
TI  - Replication of Hepatitis E Virus (HEV) in Primary Human-Derived Monocytes and 
      Macrophages In Vitro.
LID - 10.3390/vaccines8020239 [doi]
LID - 239
AB  - HEV is the most causative agent of acute viral hepatitis globally. HEV causes 
      acute, chronic, and extrahepatic manifestations. Chronic HEV infection develops 
      in immunocompromised patients such as organ transplant patients, HIV-infected 
      patients, and leukemic patients. The source of chronic HEV infection is not 
      known. Also, the source of extrahepatic manifestations associated with HEV 
      infection is still unclear. Hepatotropic viruses such as HCV and HBV replicate in 
      peripheral blood mononuclear cells (PBMCs) and these cells become a source of 
      chronic reactivation of the infections in allograft organ transplant patients. 
      Herein, we reported that PBMCs and bone marrow-derived macrophages (BMDMs), 
      isolated from healthy donors (n = 3), are susceptible to HEV in vitro. Human 
      monocytes (HMOs), human macrophages (HMACs), and human BMDMs were challenged with 
      HEV-1 and HEV-3 viruses. HEV RNA was measured by qPCR, the marker of the 
      intermediate replicative form (ds-RNA) was assessed by immunofluorescence, and 
      HEV capsid protein was assessed by flow cytometry and ELISA. HEV infection was 
      successfully established in primary HMOs, HMACs, and human BMDMs, but not in the 
      corresponding cells of murine origin. Intermediate replicative form (ds RNA) was 
      detected in HMOs and HMACs challenged with HEV. The HEV load was increased over 
      time, and the HEV capsid protein was detected intracellularly in the HEV-infected 
      cells and accumulated extracellularly over time, confirming that HEV completes 
      the life cycle inside these cells. The HEV particles produced from the infected 
      BMDMs were infectious to naive HMOs in vitro. The HEV viral load was comparable 
      in HEV-1- and HEV-3-infected cells, but HEV-1 induced more inflammatory 
      responses. In conclusion, HMOs, HMACs, and human BMDMs are permissive to HEV 
      infection and these cells could be the source of chronic and recurrent infection, 
      especially in immunocompromised patients. Replication of HEV in human BMDMs could 
      be related to hematological disorders associated with extrahepatic 
      manifestations.
FAU - Sayed, Ibrahim M
AU  - Sayed IM
AUID- ORCID: 0000-0001-8207-6401
AD  - Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut 
      University, Assiut 71515, Egypt.
AD  - Department of Pathology, School of Medicine, University of California, San Diego, 
      CA 92093, USA.
FAU - Seddik, Mohamed Ismail
AU  - Seddik MI
AUID- ORCID: 0000-0003-4531-7880
AD  - Department of Clinical Pathology, Faculty of Medicine, Assiut University, Assiut 
      71515, Egypt.
FAU - Gaber, Marwa A
AU  - Gaber MA
AD  - Department of Medical Biochemistry, Faculty of Medicine, Assiut University, 
      Assiut 71515, Egypt.
FAU - Saber, Saber H
AU  - Saber SH
AUID- ORCID: 0000-0003-1296-2023
AD  - Laboratory of Molecular Cell Biology, Department of Zoology, Faculty of Science, 
      Assiut University, Assiut 71515, Egypt.
FAU - Mandour, Sahar A
AU  - Mandour SA
AUID- ORCID: 0000-0003-2500-0480
AD  - Department of Microbiology and Immunology, Faculty of Pharmacy, Deraya 
      University, Minia 11566, Egypt.
FAU - El-Mokhtar, Mohamed A
AU  - El-Mokhtar MA
AUID- ORCID: 0000-0003-1943-8419
AD  - Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut 
      University, Assiut 71515, Egypt.
LA  - eng
GR  - 30208/Science and Technology Development Fund/
PT  - Journal Article
DEP - 20200521
PL  - Switzerland
TA  - Vaccines (Basel)
JT  - Vaccines
JID - 101629355
PMC - PMC7349946
OTO - NOTNLM
OT  - HEV infection
OT  - PBMCs
OT  - bone marrow
OT  - capsid protein
OT  - chronic
OT  - ds-RNA
OT  - extrahepatic
OT  - hematological disorders
OT  - immune response
COIS- The authors declare no conflict of interest.
EDAT- 2020/05/28 06:00
MHDA- 2020/05/28 06:01
PMCR- 2020/05/21
CRDT- 2020/05/28 06:00
PHST- 2020/05/01 00:00 [received]
PHST- 2020/05/15 00:00 [revised]
PHST- 2020/05/18 00:00 [accepted]
PHST- 2020/05/28 06:00 [entrez]
PHST- 2020/05/28 06:00 [pubmed]
PHST- 2020/05/28 06:01 [medline]
PHST- 2020/05/21 00:00 [pmc-release]
AID - vaccines8020239 [pii]
AID - vaccines-08-00239 [pii]
AID - 10.3390/vaccines8020239 [doi]
PST - epublish
SO  - Vaccines (Basel). 2020 May 21;8(2):239. doi: 10.3390/vaccines8020239.