Contribution of gene products encoded within the unique short segment of equine herpesvirus 1 to virulence in a murine model.
The pathogenesis of three equine herpesvirus 1 (EHV-1) recombinants was assessed in a CBA mouse model. Sequences encoding the majority of glycoproteins I (gI) and E (gE) were deleted from the pathogenic EHV-1 strain RacL11 (L11deltagIdeltagE), and sequences comprising the 3859 bp deletion within the strain KyA U(S) segment, which includes genes 73 (gI), 74 (gE), and 75 (putative 10 kDa protein 75), were re-inserted into attenuated KyA (KgI/gE/75). In addition, genes gE and 75 were inserted into KyA to generate the EHV-1 recombinant KgE/75. The insertion of the 3859 bp U(S) segment was sufficient to confer virulence to KyA, as indicated by pronounced signs of clinical disease including substantial weight loss. A large plaque morphology was observed in cells infected with KgI/gE/75 compared with KyA, and a small plaque phenotype was observed in cells infected with L11deltagIdeltagE compared with RacL11. These data indicate that gI and/or gI and gE contribute to the ability of EHV-1 to spread directly from cell-to-cell. The deletion of both gI and gE from the pathogenic RacL11 strain did not reduce clinical signs of disease in infected mice, but did decrease mortality compared with RacL11. Furthermore, the insertion of genes 74 (gE) and 75 into the vaccine strain KyA did not alter the attenuated phenotype of this virus. Finally, KgI/gE/75 and RacL11 elicited the production of the proinflammatory chemokines MIP-1alpha, MIP-1beta, and MIP-2 in the lungs of infected mice, while KyA did not, suggesting that gI and/or gI and gE contribute to the up-regulation of these mediators of inflammation. These findings show that gI, and/or gI and gE restore a virulent phenotype to the EHV-1 KyA strain, and indicate that virulence factors, in addition to gI and gE, contribute to the pathogenesis of the RacL11 strain.
Frampton
Arthur R
AR
Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130-3932, USA.
Smith
Patrick M
PM
Zhang
Yunfei
Y
Matsumura
Tomio
T
Osterrieder
Nikolaus
N
O'Callaghan
Dennis J
DJ
D000818:Animals; D002460:Cell Line; D018925:Chemokines / Q000378:metabolism; D003588:Cytopathogenic Effect, Viral; D005260:Female; D006566:Herpesviridae Infections / Q000503:physiopathology / Q000662:veterinary* / Q000821:virology; D004861:Herpesvirus 1, Equid / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D006734:Horse Diseases / Q000503:physiopathology / Q000821:virology*; D006736:Horses; D051379:Mice; D008808:Mice, Inbred CBA; D023421:Models, Animal; D009154:Mutation; D051381:Rats; D011995:Recombination, Genetic; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000378:metabolism; D014774:Virulence
D018925:Chemokines; D014759:Viral Envelope Proteins