Different replication behavior of a contemporary porcine hemagglutinating encephalomyelitis virus strain Gent/PS412 compared with the historical neurotropic reference strain VW572.

Publication date: Jun 24, 2026

Porcine hemagglutinating encephalomyelitis virus (PHEV), first identified in 1957, has been described as a neurotropic virus of pigs. However, more recent strains were mainly associated with respiratory problems. This study compared the replication kinetics of the historical neurotropic PHEV strain isolated in Belgium in 1972 (VW572) with the replication kinetics of a contemporary 2020 strain (PS412; isolated from nasal secretions during a monitoring study), using RPD (rein de porc diploid) cells, nasal and ethmoidal mucosa explants, and primary porcine respiratory epithelial cells (PoRECs). EGTA was used to disrupt intercellular junctions to facilitate the access of the virus to basolateral receptors. In RPD cells, VW572 showed an early advantage in initiating infection, whereas PS412 exhibited stronger replication and viral release at later stages, highlighting distinct replication dynamics between the two strains. The replication kinetics of both strains in nasal explants and PoRECs did not differ significantly. In ethmoidal explants, PHEV only replicated in sustentacular cells with VW572 infecting more cells than PS412. EGTA treatment had no effect on the PHEV infection in nasal explants but significantly increased in PoRECs and ethmoidal explants for VW572, suggesting a stronger reliance on basolateral receptors in sustentacular cells. Genomic analysis identified 2 spike protein mutations that led to amino acid changes at the receptor binding site: N512K, K576E. These changes switched the regional polarity on the surface of the spike protein that may affect the PHEV receptor use. In conclusion, the historical and contemporary PHEV isolates VW572 and PS412 replicate differently in the respiratory/neural tissues of the upper respiratory tract which may be associated with amino acid variations in the receptor binding domain of the spike protein.

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Concepts Keywords
Belgium Animals
Hemagglutinating Belgium
Mucosa Betacoronavirus 1
Pigs Coronavirus Infections
Ps412 coronavirus spike protein
Deltacoronavirus
Epithelial Cells
ethmoidal mucosa explant
nasal mucosa explant
PHEV
PoRECs
RPD
Swine
Swine Diseases
Virus Replication
virus replication
virus strain-dependent pathogenesis
virus tropism

Semantics

Type Source Name
disease MESH encephalomyelitis
disease MESH strain
disease MESH infection
pathway REACTOME Reproduction
disease MESH included
disease MESH vomiting
disease MESH anorexia
disease MESH emaciation
drug DRUGBANK Saquinavir
drug DRUGBANK ANX-510
pathway KEGG Endocytosis
drug DRUGBANK Aminosalicylic Acid
pathway KEGG Viral replication
disease MESH glass
drug DRUGBANK Streptomycin
drug DRUGBANK Phosphate ion
disease MESH PBS
drug DRUGBANK Calcium
drug DRUGBANK Magnesium
disease MESH hpi
drug DRUGBANK Pentobarbital
disease MESH body weight
drug DRUGBANK Gentamicin
drug DRUGBANK Amphotericin B
drug DRUGBANK Medical air
drug DRUGBANK Glycine
drug DRUGBANK Water
drug DRUGBANK Glutamic Acid
drug DRUGBANK Benzylpenicillin
pathway REACTOME Digestion
drug DRUGBANK Selenium
drug DRUGBANK Ethanolamine
drug DRUGBANK Coenzyme M
drug DRUGBANK Methylcellulose
pathway REACTOME Apoptosis
disease MESH Ger
drug DRUGBANK Biotin
drug DRUGBANK Glycerin
disease MESH lam
disease MESH dis
disease MESH IBM
pathway KEGG Tight junction
disease MESH ics
drug DRUGBANK Iron
drug DRUGBANK L-Asparagine
drug DRUGBANK L-Lysine
disease MESH syndromes
disease MESH dehydration
disease MESH weight loss
disease MESH ataxia
disease MESH hyperesthesia
disease MESH tremors
disease MESH death
disease MESH Coronavirus Infections
disease MESH Swine Diseases

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