OmniVira

Reciprocal cross-species infection potential of human and domestic cat hepatitis B viruses.

Qingyan Wu1 Anna Beer2 Zaichao Xu3 Zhe Zhang4 Xinyi Tang1 Wanchen Liu5 Hailing Deng1 Wanpo Zhang5 Yuchen Xia3 Stephan Urban2,6 Zhenfeng Zhang1,7 Yi Ni2,6
Affiliations 7 institutions
  1. School of Public Health and Emergency Management, School of Medicine, Southern University of Science and Technology, Shenzhen, China.
  2. Department of Infectious Diseases, Molecular Virology, University Hospital Heidelberg, Heidelberg, Germany.
  3. State Key Laboratory of Virology and Biosafety, Hubei Provincial Research Center for Basic Biological Sciences and Hubei Province Key Laboratory of Allergy and Immunology, Institute of Medical Virology, TaiKang Center for Life and Medical Sciences, TaiKang Medical School, Wuhan University, Wuhan, China.
  4. College of Animal Science and Technology, Yangtze University, Jingzhou, China.
  5. College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
  6. German Center for Infection Research (DZIF), Heidelberg Partner Site, Heidelberg, Germany.
  7. SUSTech Homeostatic Medicine Institute, School of Medicine, Southern University of Science and Technology, Shenzhen, China.
PMID42821865 DOI10.1097/HEP.0000000000001877 Year2026 Journal Hepatology (Baltimore, Md.) Hepatology Languageeng Publication statusActive
Active Last checked 2026-10-03 03:30:43 Source: NCBI PubMed

Abstract

The host tropism of human hepatitis B virus (HBV) limits cross-species transmission and hampers animal model development. Recently identified domestic cat hepatitis B virus (DCHBV) shares high similarity with HBV in viral receptor-binding motifs and their cognate receptor, sodium taurocholate co-transporting polypeptide (NTCP), suggesting potential for cross-species transmission. This study aimed to assess the reciprocal transmission capacity between HBV and DCHBV and identify key determinants of host specificity. Transfection of Huh7 cells with a DCHBV infectious clone alone, or co-transfection with hepatitis delta virus (HDV) cDNA, produced DCHBV or HDV pseudotyped with DCHBV envelope proteins (DCHDV), respectively. Cross-species infection was assessed using HepG2 cells expressing human or cat NTCP (HepG2-hNTCP/cNTCP), as well as primary human or cat hepatocytes (PHH/PCH). HBV and HDV efficiently infected HepG2-cNTCP cells and PCH. In contrast, DCHBV/DCHDV failed to infect HepG2-hNTCP cells and PHH, despite successful infection of PCH. All the infections could be inhibited by the myristoylated preS1/2-48 peptide, indicating that cNTCP is the bona fide receptor for DCHBV infection. Inefficient internalization may restrict DCHBV/DCHDV infection of human hepatocytes. Using chimeric envelope proteins, we found that the region spanning residues 16-49 of DCHBV preS1 restricts its transmission to human hepatocytes. Additionally, overexpression of cat orthologs of the proposed HBV cofactors EGFR and NRP1 did not rescue the infection. These findings suggest a marginal zoonotic risk of DCHBV for humans and support domestic cats as a potential immunocompetent animal model for HBV research.

Supporting text Virus Host Location
animal model 6 hepadnavirus 1 host tropism 8 NTCP 1 viral hepatitis 1 virus entry 11

Evidence records

5 total
Experimental Infection
3 records · 1 evidence types
Evidence type Host Range Experiment
3 records
OVE12294 Host Range Experiment
Key finding

HBV and HDV efficiently infected HepG2 cells expressing cat NTCP and primary cat hepatocytes.

Virus
Hepatitis B virus Deltavirus
Host
HepG2-cNTCP cells Experimental system PCH Experimental system
Location
Not specified
Supporting text

HBV and HDV efficiently infected HepG2-cNTCP cells and PCH.

Method
infection assay | NTCP receptor expression system (cNTCP) | primary hepatocyte infection | receptor-blocking with myristoylated preS1/2-48 peptide
Experimental system
Cell-culture host-range infection assays using HepG2 cells expressing cat NTCP and primary cat hepatocytes
OVE12295 Host Range Experiment
Key finding

DCHBV and DCHDV failed to infect HepG2 cells expressing human NTCP and primary human hepatocytes but successfully infected primary cat hepatocytes.

Virus
DCHBV DCHDV
Host
HepG2-hNTCP cells Experimental system PHH Experimental system PCH Experimental system
Location
Not specified
Supporting text

DCHBV/DCHDV failed to infect HepG2-hNTCP cells and PHH, despite successful infection of PCH.

Method
infection assay | NTCP receptor expression system (hNTCP) | primary hepatocyte infection | receptor-blocking with myristoylated preS1/2-48 peptide
Experimental system
Cell-culture and primary hepatocyte host-range infection assays comparing human versus cat hepatocyte systems
OVE12296 Host Range Experiment
Key finding

Overexpression of cat EGFR and NRP1 in human hepatocytes did not rescue DCHBV infection.

Virus
DCHBV
Host
human Homo sapiens Experimental system
Location
Not specified
Supporting text

Additionally, overexpression of cat orthologs of the proposed HBV cofactors EGFR and NRP1 did not rescue the infection.

Method
overexpression of cat EGFR and NRP1 | infection assay
Experimental system
Cofactor overexpression in human hepatocyte-based infection assay
Functional Mechanism
2 records · 2 evidence types
Evidence type Receptor Usage
1 records
OVE12297 Receptor Usage
Key finding

DCHBV uses cat NTCP (cNTCP) as its functional entry receptor, as shown by inhibition with the myristoylated preS1/2-48 peptide.

Virus
DCHBV
Host
domestic cat Felis catus Experimental system HepG2-cNTCP Experimental system primary cat hepatocytes (PCH) Experimental system
Location
Not specified
Supporting text

All the infections could be inhibited by the myristoylated preS1/2-48 peptide, indicating that cNTCP is the bona fide receptor for DCHBV infection.

Method
peptide inhibition with myristoylated preS1/2-48 | infection of HepG2 cells expressing cat NTCP (HepG2-cNTCP) | infection of primary cat hepatocytes (PCH) | HDV pseudotyping with DCHBV envelope proteins (DCHDV)
Receptors
cNTCP | sodium taurocholate co-transporting polypeptide
Host factors
EGFR | NRP1
Evidence type Molecular Adaptation
1 records
OVE12298 Molecular Adaptation
Key finding

Residues 16–49 of the DCHBV preS1 region restrict DCHBV transmission to human hepatocytes, indicating a molecular determinant of host specificity.

Virus
DCHBV
Host
Not specified
Location
Not specified
Supporting text

Using chimeric envelope proteins, we found that the region spanning residues 16-49 of DCHBV preS1 restricts its transmission to human hepatocytes.

Genes or proteins
preS1 | envelope proteins
Receptors
NTCP
Mechanism types
receptor binding | host-range expansion | host entry | tissue tropism