Vaccinia virus semaphorin A39R is a 50-55 kDa secreted glycoprotein that affects the outcome of infection in a murine intradermal model

Vaccinia virus (VV) protein A39R has amino acid similarity to the extracell ular domain of a glycosylphosphatidylinositol-linked cell surface semaphori n (SEMA7A/CDw108) that has an immunological expression profile and binding properties, thereby implicating A39R as an immunomodulator. Previously, a c losely related A39R protein expressed by ectromelia virus was shown to indu ce cytokine production and up-regulate ICAM-1 expression in mouse monocytes in vitro. In this study, we show that the A39R gene of VV strain Copenhage n (COP) encodes a 50-55 kDa secreted glycoprotein and is expressed late dur ing infection. The A39R protein was secreted by eight of 15 strains of VV, but not by strain Western Reserve (WR). To analyse the VV A39R function, se veral recombinant viruses were made, including an A39R deletion mutant of V V COP and a WR mutant containing the A39R sequence from COP. Loss of the ge ne from COP did not affect virus growth in vitro, or VV virulence in a mous e intranasal model, and had only a slight effect on lesion size in an intra dermal model. In contrast, expression of COP A39R by VV WR was associated w ith an increase in the severity and persistence of skin lesions after intra dermal infection of mice. Finally, a histological examination of mouse skin infected with recombinant viruses suggested that A39R has direct or indire ct pro-inflammatory properties.