Human inborn errors of immunity to oncogenic viruses

Area of Science:

• Immunology
• Virology
• Oncology

Background:

• Oncoviruses are viruses capable of causing tumors in humans.
• Seven viruses are recognized as oncogenic: EBV, KSHV (HHV8), HPV, HBV, HCV, HTLV-1, and MCPyV.
• Inborn errors of immunity (IEI) predispose individuals to infectious diseases, including those caused by oncoviruses.

Purpose of the Study:

• To review current knowledge on IEI predisposing to severe oncovirus infections.
• To highlight the understanding gained from IEI studies regarding EBV, HHV8, and HPV.
• To identify the knowledge gaps concerning genetic factors for HBV, HCV, HTLV-1, and MCPyV predisposition.

Main Methods:

• Literature review of studies on inborn errors of immunity and oncovirus infections.
• Analysis of known mechanisms controlling EBV, HHV8, and HPV infections in IEI patients.
• Identification of oncoviruses where genetic predisposition to severe manifestations is not yet understood.

Main Results:

• IEI studies have elucidated key mechanisms for controlling Epstein Barr virus (EBV), Kaposi sarcoma-associated herpesvirus (KSHV/HHV8), and human papillomaviruses (HPVs).
• The human genetic factors that predispose individuals to oncogenic hepatitis B virus (HBV), hepatitis C virus (HCV), human T-lymphotropic virus-1 (HTLV-1), and Merkel cell polyomavirus (MCPyV) remain largely unknown.
• Clinical outcomes of oncovirus infections in IEI patients range from asymptomatic to invasive cancers.

Conclusions:

• IEI research significantly advances understanding of oncovirus control, particularly for EBV, HHV8, and HPV.
• Further research is needed to identify genetic factors underlying susceptibility to severe infections with oncogenic HBV, HCV, HTLV-1, and MCPyV.
• Understanding these genetic predispositions is crucial for preventing and managing virus-associated cancers in vulnerable populations.