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Literature detail

De novo recovery of Ghana virus, an African bat Henipavirus, reveals differential tropism and attenuated pathogenicity compared to Nipah virus.

Griffin D Haas1 Olivier Escaffre2 Rebecca A Reis1 Terry L Juelich2 Jennifer K Smith2 Lihong Zhang2 Birte K Kalveram3 Axel A Guzmán-Solís1 Dariia Vyshenska4 William Klain1 Alexander L Greninger4 Alexander N Freiberg5 Benhur Lee6
Affiliations 6 institutions
  1. Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  2. Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.
  3. Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
  4. Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
  5. Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA. Electronic address: [email protected].
  6. Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: [email protected].
PMID 41824449 2026 Cell Rep eng ppublish
PubMed DOI Browse context

Article

Publication summary

Henipaviruses (HNVs) like Nipah virus (NiV) and Hendra virus (HeV) represent severe zoonotic threats. Ghana virus (GhV), identified in 2012, is the only African bat henipavirus with a near-complete genome assembly. However, without isolates in culture, GhV biology, pathogenicity, and zoonotic potential remain poorly understood. Using reverse genetics, we recovered a full-length infectious clone of GhV at BSL-4 following rational reconstruction of its incomplete 3' leader and modification of a non-canonical transcriptional initiation site. GhV demonstrated restricted receptor tropism (ephrin-B2 but not ephrin-B3) and distinct innate immune antagonism. Replication was attenuated in primary human cells but was enhanced in bat cells. In Syrian golden hamsters, GhV infection caused no disease or mortality. Furthermore, a chimeric NiV encoding the GhV receptor-binding protein was completely attenuated in vivo, implicating ephrin-B3 receptor usage as a critical determinant of HNV pathogenesis. These findings elucidate GhV zoonotic potential and inform strategies for virus surveillance and control.

BSL-4 CP: microbiology emerging viruses Ephrin-B2 Ephrin-B3 Ghana virus henipavirus Nipah virus reverse genetics viral pathogenesis zoonotic potential Chiroptera Henipavirus Nipah Virus Viral Tropism Animals Cricetinae Ephrin-B2

Structured evidence records

Evidence records

6 total
Host Range Experiment 2 records
Host Range Experiment Extraction confidence 0.95
Key finding

Ghana virus replicated poorly in human cells, more strongly in bat cells, and did not cause disease in Syrian golden hamsters, demonstrating host-specific restriction in replication and pathogenesis.

Virus
GhV
Location
Not specified
Supporting text

Replication was attenuated in primary human cells but was enhanced in bat cells. In Syrian golden hamsters, GhV infection caused no disease or mortality.

Method
reverse genetics; virus replication assay
Experimental system
in vitro cell culture
Host Range Experiment Extraction confidence 0.95
Key finding

Ghana virus caused no disease or mortality in experimentally infected Syrian golden hamsters, indicating limited pathogenicity in this mammalian model.

Virus
GhV
Location
Not specified
Supporting text

Replication was attenuated in primary human cells but was enhanced in bat cells. In Syrian golden hamsters, GhV infection caused no disease or mortality.

Method
experimental infection
Experimental system
in vivo animal experiment
Molecular Adaptation 2 records
Molecular Adaptation Extraction confidence 0.90
Key finding

Ghana virus shows receptor binding adaptation to ephrin-B2 but not ephrin-B3 and differential replication in human and bat cells, indicating molecular mechanisms underlying host-specific tropism and attenuation.

Virus
GhV
Host
Not specified
Location
Not specified
Supporting text

GhV demonstrated restricted receptor tropism (ephrin-B2 but not ephrin-B3) and distinct innate immune antagonism. Replication was attenuated in primary human cells but was enhanced in bat cells.

Genes or proteins
receptor-binding protein
Receptors
ephrin-B2; ephrin-B3
Mechanism types
receptor_binding; tissue_tropism; pathogenicity; immune_escape
Molecular Adaptation Extraction confidence 0.90
Key finding

Replacement of Nipah virus receptor-binding protein with that of Ghana virus led to complete attenuation, showing that ephrin-B3 receptor usage drives pathogenicity differences among henipaviruses.

Virus
NiV
Host
Not specified
Location
Not specified
Supporting text

A chimeric NiV encoding the GhV receptor-binding protein was completely attenuated in vivo, implicating ephrin-B3 receptor usage as a critical determinant of HNV pathogenesis.

Genes or proteins
receptor-binding protein
Receptors
ephrin-B3
Mechanism types
receptor_binding; pathogenicity
Receptor Usage 2 records
Receptor Usage Extraction confidence 1.00
Key finding

Ghana virus binds ephrin-B2 but not ephrin-B3, indicating restricted receptor tropism relative to Nipah virus.

Virus
GhV
Host
Not specified
Location
Not specified
Supporting text

GhV demonstrated restricted receptor tropism (ephrin-B2 but not ephrin-B3) and distinct innate immune antagonism.

Receptors
ephrin-B2
Receptor Usage Extraction confidence 1.00
Key finding

Ephrin-B3 receptor usage contributes critically to Nipah virus pathogenicity compared to Ghana virus.

Virus
NiV
Host
Not specified
Location
Not specified
Supporting text

Furthermore, a chimeric NiV encoding the GhV receptor-binding protein was completely attenuated in vivo, implicating ephrin-B3 receptor usage as a critical determinant of HNV pathogenesis.

Receptors
ephrin-B3