Virology

Biography

Biography: Mugdha Vasireddi

Abstract

Herpes B virus, endemic in macaques, is a simplex virus like HSV-1 in its disease manifestation in natural hosts. Zoonotic infection of herpes B virus in humans, however, results in 80% fatality without timely antiviral intervention. Our previous studies revealed that herpes B virus infected human cells do not down-regulate MHC Class I molecules on the surface of infected cells, but rather up-regulate NK cell inhibitory MHC Class Ib molecules, HLA-E and HLA-G. This induction of NK cell inhibitory markers is an indicator of impairment of NK cells. Therefore, we hypothesized that herpes B virus escapes natural killer (NK) cell lysis in zoonotically infected humans by inhibiting NK cell activation. To test this hypothesis, we used a cell culture model system to examine whether herpes B virus infected HFF cells and herpes B virus infected HFFs co-cultured with peripheral blood mononuclear cells (PBMCs) generated the production of NK cell-activating cytokines and chemokines. Analysis of results revealed that herpes B virus infection resulted in down-regulation of NK cell-activating cytokines and chemokines, i.e., IFN-α, IP-10, IL-8, and MCP-1. Next, we measured NK cell activity during herpes B virus infection by quantifying the expression of cytotoxic granules (granzyme and perforin) and cytokine (TNF-α and IFN-γ) expression. Our results demonstrated that NK cells with or without stimulation during herpes B virus infection failed to express cytotoxic granules or cytokines supporting our hypothesis that NK cell activity is impaired during human infection. In addition, we also examined herpes B virus titers in the HFF cells co-cultured with IFN-α stimulated or un-stimulated NK cells. Our results suggested that NK cells were incapable of restricting herpes B virus infection even when stimulated with IFN-α. Therefore, these results suggest that NK cells during B virus infection are rendered inactive