title: Bovine herpesvirus type 1 (BHV-1) mutant lacking U(L)49.5 luminal domain residues 30-32 and cytoplasmic tail residues 80-96 induces more rapid onset of virus neutralizing antibody and cellular immune responses in calves than the wild-type strain Cooper.
abstract: Bovine herpesvirus type 1 (BHV-1) envelope protein U(L)49.5 inhibits transporter associated with antigen processing (TAP) and down-regulates cell-surface expression of major histocompatibility complex (MHC) class I molecules to promote immune evasion. Earlier, we have constructed a BHV-1U(L)49.5Δ30-32 CT-null virus and determined that in the infected cells, TAP inhibition and MHC-I down regulation properties of the virus are abolished. In this study, we compared the pathogenicity and immune responses in calves infected with BHV-1U(L)49.5Δ30-32 CT-null and BHV-1 wt viruses. Following primary infection, both BHV-1 wt and BHV-1U(L)49.5Δ30-32 CT-null virus replicated in the nasal epithelium with very similar yields. BHV-1 antigen-specific CD8+ T cell proliferation as well as CD8+ T cell cytotoxicity in calves infected with the BHV-1U(L)49.5Δ30-32 CT-null virus peaked by 7 dpi (P<0.05) which is 7 days earlier than that of BHV-1 wt-infected calves. Further, virus neutralizing antibody (VN Ab) titers and IFN-γ producing peripheral blood mononuclear cells (PBMCs) in the U(L)49.5 mutant virus-infected calves, also peaked 7 days (IFN-γ; P<0.05) and 14 days (VN Ab; P<0.05) earlier, respectively. Therefore, relative to wt in the BHV-1U(L)49.5 mutant virus-infected calves, primary neutralizing antibody and cellular immune responses were induced significantly more rapidly.
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA.
authors.forename: Huiyong
authors.initials: H
authors.lastname: Wei
authors.forename: Junyun
authors.initials: J
authors.lastname: He
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Paulsen
authors.forename: Shafiqul I
authors.initials: SI
authors.lastname: Chowdhury
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002417:Cattle / Q000276:immunology* / Q000821:virology*; D002418:Cattle Diseases / Q000276:immunology; D006566:Herpesviridae Infections / Q000276:immunology / Q000662:veterinary; D007242:Herpesvirus 1, Bovine / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D007111:Immunity, Cellular; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D009154:Mutation; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology; D014779:Virus Replication
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D050505:Mutant Proteins; C099455:UL49.5 protein, bovine herpesvirus type 1; D014759:Viral Envelope Proteins; D014765:Viral Vaccines