Human inborn errors of immunity to oncogenic viruses

Abstract

Oncoviruses are viruses that can cause tumors. Seven viruses are currently recognized as oncogenic in humans: Epstein Barr virus (EBV), Kaposi sarcoma-associated herpesvirus (KSHV, also known as HHV8), human papillomaviruses (HPVs), hepatitis B virus (HBV), hepatitis C virus (HCV), human T-lymphotropic virus-1 (HTLV-1), and Merkel cell polyomavirus (MCPyV). The clinical phenotypes resulting from infection with these oncoviruses range from asymptomatic infection to invasive cancers. Patients with inborn errors of immunity (IEI) are prone to the development of infectious diseases caused by a narrow or broad spectrum of pathogens, including oncoviruses in some cases. Studies of patients with IEI have deepened our understanding of the non-redundant mechanisms underlying the control of EBV, HHV8 and HPV infections. The human genetic factors conferring predisposition to oncogenic HBV, HCV, HTLV-1 and MCPyV manifestations remain elusive. We briefly review here what is currently known about the IEI conferring predisposition to severe infection with oncoviruses.

Figure :

Schematic representation of the oncogenic process in immunocompetent and immunodeficient individuals. Insights in non-redundant immune mechanisms for the control of oncoviruses gained from the study of inborn errors of immunity are listed in the upper right box. Most of them come from the genetic studies of HPV, EBV, and to lesser extend HHV8 infections. Genetic factors predisposing to severe HBV, HCV, MCPyV and HTLV1 remain largely unknown.