Oncogenic herpesviruses sending mixed signals.

Abstract

Human herpesvirus infections are generally asymptomatic in immune-competent hosts; however, immune dysfunction can unveil inherent oncogenic properties associated with Epstein-Barr virus (EBV) and Kaposi’s sarcoma herpesvirus (KSHV) infection. Although these viruses were first discovered in human tumor specimens in 1964 and 1994, respectively, it was discovered later on that large proportions of the human population are persistently infected with EBV and to a lesser extent KSHV. To colonize immune-competent hosts, EBV and KSHV drive proliferation of newly infected cells by latent transcription programs. EBV infection is principally limited to B cells, and few infected epithelial cells in the oral mucosa that produce infectious virus for host–host transmission via the saliva. In contrast, KSHV has a broader spectrum of target cells while transmission and life cycle are less well understood. However, these viruses share a host-colonization and persistence strategy that involves activation of NF-κB, a critical survival factor for developing human B cells. Deregulated NF-κB activation can cause uncontrolled B-cell proliferation and secretion of proinflammatory factors that support cancer development. Apart from protumorigenic soluble factors, many tumor cells release endosome-derived vesicles, called exosomes, which mediate intercellular communication. In PNAS, Meckes et al. describe that EBV- and KSHV-infected lymphoma cells secrete exosomes with distinct repertoires of cellular proteins (1). In light of recent studies demonstrating that tumor cell-derived exosomes exert protumorigenic signaling properties (2), the data presented by Meckes et al. suggest that virus and tumor cells share common strategies in shaping a permissive microenvironment by modulating the cargo of secreted exosomes (Fig. 1).