Microarray analysis of transcriptional responses to infection by herpes simplex virus types 1 and 2 and their US3-deficient mutants

Herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) induce similar responses in infected cells and animals but differ in several significant respects. Previous studies have shown that defects in the US3-encoded protein kinase greatly affect both viruses in their interactions with cells and hosts. To investigate the impact of infection with HSV-1, HSV-2 and their US3-deficient mutants (ΔUS3) on cellular transcriptional responses, we performed a global microarray analysis on human epithelial HEp-2 cells that were mock-infected, or infected with wild-type (WT) HSV-1, HSV-2 and their ΔUS3 mutants. Among 54,765 probe sets examined, only 1156 (approximately 2.1%) and 2006 (approximately 3.7%) genes increased by at least fourfold at 9 h postinfection in WT HSV-1 and HSV-2-infected cells, respectively. Unexpectedly, HSV-2 infection increases mRNA levels for a larger number of cellular genes than HSV-1 infection. Additionally, ΔUS3 infection upregulated the expression of a larger number of cellular genes than WT infection. The genes affected by HSV infection were assigned to various groups of functional classes and cellular pathways. We have thus identified cellular genes whose expression was similarly or differently changed by infection with each virus.