Neutralization Activity of the Vaccinia Virus B18R protein against the Human Interferon Alpha protein family

Abstract:

The human interferon alpha family is composed of 13 closely related genes that all signal through a common interferon alpha receptor complex (IFNAR). Infected cells produce a combination of IFN-α proteins that are secreted and subsequently bind with IFNAR receptors on neighboring cells effectively limiting virus replication levels. The expression level of each IFN-α protein can vary in virus- and cell-dependent manners. The IFN-α proteins have been shown to bind the IFNAR complex with varying affinities and also exhibit unique subtype-specific biological activities. Vaccinia virus produces the B18R protein that can function as different type I IFNs, including IFN-α. Moreover, the protein can function as a decoy in solution or when complexed to cells. This study investigated the neutralization capacity of the B18R soluble receptor decoy against each individual member of the IFN-α family to determine whether the virus or host interactions were biased against specific subtypes. The neutralization IC50 values varied substantially between B18R treatment groups (solution pre-complex or cell pre-complex) and between the individual IFN-α subtypes. B18R treatment did not block IFN-γ or IL-29 (IFN-λ) demonstrating the neutralization was type I IFN-specific. Overall, these results provide insight into virus-host interactions and may suggest a possible reason for apparent redundancy within the IFN-α gene family.

 

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Neutralization Activity of the Vaccinia Virus B18R protein against the Human Interferon Alpha protein family

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