The role of the secreted glycoprotein G in equine herpesvirus type 1 (EHV-1) immune modulation and virulence
Final Report Abstract
The overall objective of this proposal was first to identify the domains in EHV-1/EHV-4 gG important for binding to chemokines. We had previously demonstrated that gG of EHV-1 modulates the host’s immune response by binding to chemokines and as such, contributes to virulence. Since gG of the closely related EHV-4 does not exhibit properties consistent with a viral chemokine binding protein (vCKBP), and, interestingly, does not cause a viremia, we compared these two closely related molecules and identified the domains that are important for binding to chemokines and interference with migration of host immune cells. This was achieved by a combination of in vitro and in vivo studies. First, in vitro studies were conducted to identify the domains in EHV-1 gG important for binding to chemokines. Secondly, various virus mutants with modifications in the important binding domains in gG were generated and their immunomodulatory potential was tested in vivo in a murine model of EHV-1 infection.
Publications
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(2008). Alphaherpesviruses and chemokines: pas de deux not yet brought to perfection. J Virol. 82(13):6090-7
Van de Walle GR, Jarosinski KW, Osterrieder N
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(2008). CCL3 and viral chemokine-binding protein gG modulate pulmonary inflammation and virus replication during equine herpesvirus 1 infection. J Virol. 82(4):1714-22
Van de Walle GR, Sakamoto K, Osterrieder N
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(2009) Analysis of the herpesvirus chemokine-binding glycoprotein G residues essential for chemokine binding and biological activity. J Biol Chem. 284(9):5968-76
Van de Walle GR, Kaufer BB, Chbab N, Osterrieder N
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(2010) Pathogenic potential of equine alphaherpesviruses: the importance of the mononuclear cell compartment in disease outcome. Vet Microbiol. 143(1):21-8
Osterrieder N, Van de Walle GR
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(2013) The role of secreted glycoprotein G of equine herpesvirus type 1 and type 4 (EHV-1 and EHV-4) in immune modulation and virulence. Virus Res. 169(1):203-211
Thormann N, Van de Walle GR, Azab W, Osterrieder N
