title: Immunization with Attenuated Equine Herpesvirus 1 Strain KyA Induces Innate Immune Responses That Protect Mice from Lethal Challenge.
abstract: Equine herpesvirus 1 (EHV-1) is a major pathogen affecting equines worldwide. The virus causes respiratory disease, abortion, and, in some cases, neurological disease. EHV-1 strain KyA is attenuated in the mouse and equine, whereas wild-type strain RacL11 induces severe inflammation of the lung, causing infected mice to succumb at 4 to 6 days postinfection. Our previous results showed that KyA immunization protected CBA mice from pathogenic RacL11 challenge at 2 and 4 weeks postimmunization and that KyA infection elicited protective humoral and cell-mediated immune responses. To investigate the protective mechanisms of innate immune responses to KyA, KyA-immunized mice were challenged with RacL11 at various times postvaccination. KyA immunization protected mice from RacL11 challenge at 1 to 7 days postimmunization. Immunized mice lost less than 10% of their body weight and rapidly regained weight. Virus titers in the lungs of KyA-immunized mice were 1,000-fold lower at 2 days post-RacL11 challenge than virus titers in the lungs of nonimmunized mice, indicating accelerated virus clearance. Affymetrix microarray analysis revealed that gamma interferon (IFN-γ) and 16 antiviral interferon-stimulated genes (ISGs) were upregulated 3.1- to 48.2-fold at 8 h postchallenge in the lungs of RacL11-challenged mice that had been immunized with KyA. Murine IFN-γ inhibited EHV-1 infection of murine alveolar macrophages and protected mice against lethal EHV-1 challenge, suggesting that IFN-γ expression is important in mediating the protection elicited by KyA immunization. These results suggest that EHV-1 KyA may be used as a live attenuated EHV-1 vaccine as well as a prophylactic agent in horses.
  
  
  
  Viral infection of cells initiates a signal cascade of events that ultimately attempts to limit viral replication and prevent infection through the expression of host antiviral proteins. In this study, we show that EHV-1 KyA immunization effectively protected CBA mice from pathogenic RacL11 challenge at 1 to 7 days postvaccination and increased the expression of IFN-γ and 16 antiviral interferon-stimulated genes (ISGs). The administration of IFN-γ blocked EHV-1 replication in murine alveolar macrophages and mouse lungs and protected mice from lethal challenge. To our knowledge, this is the first report of an attenuated EHV-1 vaccine that protects the animal at 1 to 7 days postimmunization by innate immune responses. Our findings suggested that IFN-γ serves as a novel prophylactic agent and may offer new strategies for the development of anti-EHV-1 agents in the equine.
authors.affiliation: Department of Microbiology and Immunology and Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA skim1@lsuhsc.edu.
authors.forename: Seong K
authors.initials: SK
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Immunology and Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.
authors.forename: Akhalesh K
authors.initials: AK
authors.lastname: Shakya
authors.affiliation: Department of Microbiology and Immunology and Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: O'Callaghan
mesh_terms: D000818:Animals; D001835:Body Weight; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D006566:Herpesviridae Infections / Q000517:prevention & control* / Q000821:virology; D004861:Herpesvirus 1, Equid / Q000276:immunology*; D007113:Immunity, Innate; D008168:Lung / Q000821:virology; D008808:Mice, Inbred CBA; D046228:Microarray Analysis; D013997:Time Factors; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D019562:Viral Load; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D014613:Vaccines, Attenuated; D014765:Viral Vaccines