Lymphotropic Viruses: Chronic Inflammation and Induction of Cancers

Simple Summary Infection with viruses such as HTLV-1, EBV and KSHV has been linked to many cancers, including leukemias and lymphomas in humans worldwide. These viruses establish life-long latency after initial infections. Currently, there are no effective treatments for the prevention of cancers associated with these viruses. Studies have shown that chronic inflammation mediated by the transcription factors STAT3 and NF-kappa B in HTLV-1, EBV and KSHV-infected cells play critical roles in the development of viral-associated cancers. Inhibition of STAT3 and NF-kappa B activation in cells harboring these latent viruses leads to their destruction and the production of new virus particles. De novo infection by these viruses induces rapid NF-kappa B and STAT3 activation and creates a favorable environment for virus entry into host cells and viral latency. However, the host factors and the mechanisms required for rapid NF-kappa B and STAT3 activation during de novo infection and latency by these viruses are largely unknown. In this review, we will discuss the mechanisms that are specifically involved in NF-kappa B and STAT3 activation during de novo infection and latency by KSHV, EBV and HTLV-1. Inflammation induced by transcription factors, including Signal Transducers and Activators of Transcription (STATs) and NF-kappa B, in response to microbial pathogenic infections and ligand dependent receptors stimulation are critical for controlling infections. However, uncontrolled inflammation induced by these transcription factors could lead to immune dysfunction, persistent infection, inflammatory related diseases and the development of cancers. Although the induction of innate immunity and inflammation in response to viral infection is important to control virus replication, its effects can be modulated by lymphotropic viruses including human T-cell leukemia virus type 1 (HTLV-1), Kappa aposi's sarcoma herpesvirus (KSHV), and Epstein Barr virus (EBV) during de novo infection as well as latent infection. These lymphotropic viruses persistently activate JAK-STAT and NF-kappa B pathways. Long-term STAT and NF-kappa B activation by these viruses leads to the induction of chronic inflammation, which can support the persistence of these viruses and promote virus-mediated cancers. Here, we review how HTLV-1, KSHV and EBV hijack the function of host cell surface molecules (CSMs), which are involved in the regulation of chronic inflammation, innate and adaptive immune responses, cell death and the restoration of tissue homeostasis. Thus, better understanding of CSMs-mediated chronic activation of STATs and NF-kappa B pathways in lymphotropic virus-infected cells may pave the way for therapeutic intervention in malignancies caused by lymphotropic viruses.