Getting the message direct manipulation of host mRNA accumulation during gammaherpesvirus lytic infection

The Gammaherpesvirinae subfamily of herpesviruses comprises lymphotropic viruses, including the oncogenic human pathogens Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus. During lytic infection, gammaherpesviruses manipulate host gene expression to optimize the cellular environment for viral replication and to evade the immune response. Additionally, although a lytically infected cell will itself be killed in the process of viral replication, lytic infection can contribute to pathogenesis by inducing the secretion of paracrine factors with functions in cell survival and proliferation, and angiogenesis. The mechanisms by which these viruses manipulate host gene expression are varied and target the accumulation of cellular mRNAs and their translation, signaling pathways, and protein stability. Here, we discuss how gammaherpesviral proteins directly influence host mRNA biogenesis and stability, either selectively or globally, in order to fine-tune the cellular environment to the advantage of the virus. Appreciation of the mechanisms by which these viruses interface with and adapt normal cellular processes continues to inform our understanding of gammaherpesviral biology and the regulation of mRNA accumulation and turnover in our own cells.