In Vivo Inhibition of Type I Interferon Transcription in Genital HSV-2 Lesions (134.72)

Abstract We performed transcriptional analysis and immunocytochemistry (ICC) of sequential biopsies of lesional tissue of immunocompetent persons with recurrent HSV-2 infection. Histologic analysis of these biopsies indicated a massive infiltration of monocytes/macrophages along with a large amount of myeloid and a small number of plasmacytoid dendritic cells in the dermis of these lesional biopsies. IFNB1 and IFN-α were weakly expressed and IFNG potently induced during time periods in which there was abundant detection of HSV-2 antigens and gene expression. Transcriptional arrays of the same anatomic area over time (newly healed, 2 and 4 weeks post healing) in which no HSV DNA/RNA or antigen was detected continued to show that IFNB1 and IFN-α were barely detectable. IFNG persisted in lesional tissue, albeit at lower levels as compared with active lesions. Interferon-stimulated genes (ISGs) were also markedly up-regulated with expression patterns more clearly resembling those in primary human fibroblasts treated by IFNG than by IFNB1. The presence of a very large number of innate cells capable of sensing HSV-2 infection and synthesizing type I IFN by both histologic and transcriptional analyses associated with extremely low levels of IFN-α and IFNB1 even in the earliest lesional biopsies suggests a potent alteration in host defense during HSV-2 infection in vivo. This block of type I IFN by HSV-2 may be a major factor in allowing the virus to breakthrough host mucosal defenses.