Varicella zoster virus decreases transcription and translation of STAT1 and blocks translocation of pSTAT1 to the nucleus in cerebrovascular adventitial fibroblasts. (P6149)

Abstract

Varicella zoster virus (VZV) is the only human virus known to replicate in cerebral arteries and produce stroke. After reactivation, virus travels transaxonally from ganglia and initially infects the arterial adventitia. To analyze the virus-host relationship, we infected primary human cerebrovascular adventitial fibroblasts with VZV and studied the interferon-α initiated STAT pathway, which is commonly activated after virus infection. Quantitative PCR showed that expression of STAT1, STAT2 and Mx1 mRNA were significantly decreased in VZV-infected, but not uninfected adventitial fibroblasts (p<0.05). Western blotting confirmed decreased STAT1 and Mx1 expression in VZV-infected fibroblasts compared to uninfected cells. Although Western blotting did not reveal phosphorylated STAT1 (pSTAT1) in VZV-infected cells, interferon-α is known to trigger STAT1 phosphorylation; thus, we treated uninfected adventitial fibroblasts with interferon-α, after which pSTAT1 expression was readily seen on Western blots. Furthermore, immunocytochemical staining detected pSTAT1 exclusively in the cytoplasm of VZV-infected cells. In interferon-α -treated uninfected cells, pSTAT1 was found exclusively in the nucleus, suggesting that VZV infection blocks egress of pSTAT1 from the cytoplasm to the nucleus in cerebral adventitial fibroblasts.