KSHV: pathways to tumorigenesis and persistent infection

Kaposi's sarcoma-associated herpesvirus (KSHV; also known as human herpesvirus 8) is the etiologic agent of Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. These cancers often occur in the context of immunosuppression, which has made KSHV-associated malignancies an increasing global health concern with the persistence of the AIDS epidemic. KSHV has also been linked to several acute inflammatory diseases. KSHV exists between a lytic and latent lifecycle, which allows the virus to transition between active replication and quiescent infection. KSHV encodes a number of proteins and small RNAs that are thought to inadvertently transform host cells while performing their functions of helping the virus persist in the infected host. KSHV also has an arsenal of components that aid the virus in evading the host immune response, which help the virus establish a successful lifelong infection. In this comprehensive chapter, we will discuss the diseases associated with KSHV infection, the biology of latent and lytic infection, and individual proteins and microRNAs that are known to contribute to host cell transformation and immune evasion.