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

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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