Kinome analysis reveals differential host-cell responses to West African or Central African monkeypox virus infection

Wednesday, October 26, 2011 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center	NIAID	INFECTDIS-5

* FARE Award Winner

Authors

• KJ Kindrachuk
• R Arsenault
• KN Kindrachuk
• S Napper
• JE Blaney
• PB Jahrling

Abstract

Background: Monkeypox virus (MPXV) is a member of the genus Orthopoxvirus that causes zoonotic disease with associated case fatality rates of 10-17%. Increasing incidence of MPXV and its classification as a bioterrorism agent lend credence for investigating the molecular mechanisms of disease pathogenesis. Further, infection with the Western African MPXV clade (MPXV Sierra Leone) is less severe compared to the Central African clade (MPXV Zaire). As many host responses are regulated through phosphorylation independent of transcription or translation we compared the cellular responses to infection with both MPXV clades through kinome analysis. Methods: Kinome analysis was performed with peptide arrays representing human kinase targets. Host signaling pathways were identitified by pathway over-representation. Results: Our results demonstrate that MPXV Zaire and Sierra Leone differentially modulate host signaling pathways. In comparison to MPXV Sierra Leone, MPXV Zaire repressed pathways related to immune surveillance (FAS signaling pathway), growth and differentiation (FGF signaling pathway, Akt-mediated PI3K signaling events) and apoptosis (PTEN dependent cell-cycle arrest, p53-mediated signaling). These results were confirmed biologically. Conclusions: We have demonstrated that infection with MPXV Zaire and Sierra Leone differentially modulate host signaling pathways using a novel approach and highlight potential host factors for the development of novel antiviral therapeutics.

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