Role of Filoviral Proteins in Immune Evasion and Replication

Identification: Amarasinghe, Gaya


Description

Role of Filoviral Proteins in Immune Evasion and Replication
 
Gaya K. Amarasinghe1*
1Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110
 
A hallmark of Ebola viral infection, which is shared among all Ebola viruses, is the ability to achieve a very high level of host immune suppression during early stages of infection by virally encoded multifunctional proteins. Among the virally encoded proteins, viral protein 35 (VP35) and viral protein 24 (VP24) are largely responsible for the ability of the Ebola virus to "sneak" into the host, "hide" from sentinel pattern recognition receptors, and to "attack" interferon-mediated immune responses. Events leading to viral entry and host immune evasion are complex and highly choreographed events. Additionally, comparison of amino acid changes among sequences from 1976 to the more recent outbreak (Makona/2014) points to functionally relevant variations at the host-viral interface. Recent studies, including our own, are beginning to uncover regulatory mechanisms that facilitate viral immune evasion. Our studies are also identifying key sequences within VP35 that can modulate viral replication, supporting a model where both immune evasion and viral replication functions are modulated through the multi-domain VP35 protein. We will discuss recent structural, biophysical, and cell-based studies that have defined critical interactions and regulatory mechanisms that influence immune evasion and replication functions. These findings substantially enhance our understanding of Ebola virus biology, including the biology of 2014 West Africa strains, and have significant implications for antiviral development.
 
Funding: NIH grants AI059536 to C.F.B. and AI081914 to G.K.A., R01AI123926 to GKA and CFB, R01 AI114654 to GKA, DWL, and CFB, and U19AI109945 (Basler-PI), P01AI120943 (Amarasinghe-PI) to GKA, DWL, and CFB, DTRA grant HDTRA1-12-1-0051 (to C.F.B. and G.K.A.).
 

Credits

Credits: None available.

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