The Criteria to Confirm the Role of Epstein-Barr Virus in Nasopharyngeal Carcinoma Initiation

Ai-Di Gu,Mu-Sheng Zeng,Chao-Nan Qian

doi:10.3390/ijms131013737

Abstract

Epstein-Barr virus (EBV) is associated with nasopharyngeal carcinoma (NPC), but it remains obscure whether EBV is a viral cause of, or only an accompaniment of, NPC. We will discuss the accumulated evidence pointing to the relationship between EBV infection and NPC initiation from epidemiologic, pathogenic, molecular oncogenic, and experimental animal studies. We believe that convincing evidence from these perspectives must be provided before we can ascertain the causal role of EBV infection in NPC. Specifically, (1) epidemiological studies should reveal EBV infection as a risk factor; (2) the introduction of EBV into an animal model should produce NPC; (3) in the animal model NPC, the main molecular event(s) or the involved signaling pathway(s) should be identical to that in human NPC; and (4) finally and most importantly, prevention of EBV infection or clearance of EBV from infected individuals must be able to reduce the incidence rate of NPC.

Highlights

The viral cause of an infectious disease can be established by fulfilling Koch’s postulates as modified by Rivers [1], for which six criteria are required: universal presence of virus in every diseased host, isolation from hosts, cultivation in pure culture, production of a comparable disease by injecting the virus into a suitable recipient, re-isolation of the virus, and detection of a specific immune response to the virus
Together with the long latency between primary Epstein-Barr virus (EBV) infection and nasopharyngeal carcinoma (NPC) development, these results suggest that
In order to clarify the etiological role of EBV in NPC, we believe the most convincing evidence should be the decline of the NPC incidence rate in endemic areas by prevention of EBV infection

Summary

Introduction

The viral cause of an infectious disease can be established by fulfilling Koch’s postulates as modified by Rivers [1], for which six criteria are required: universal presence of virus in every diseased host, isolation from hosts, cultivation in pure culture, production of a comparable disease by injecting the virus into a suitable recipient, re-isolation of the virus, and detection of a specific immune response to the virus. In 2003, when the new human infectious disease SARS (severe acute respiratory syndrome) broke out, these criteria helped to establish the causal relationship between SARS and SARS-associated coronavirus [2]. Unlike infectious diseases, cancer occurrence is a complex and chronic process, and the association and causative relationship between virus and carcinogenesis was debated for a long time until viruses were verified in some cancers. During the following 20 years, significant discoveries helped to establish the relationship between viruses and tumors, including the recovery of hepatitis B virus (HBV) particles in the serum of patients with hepatitis [4]; the isolation of the human T-cell leukemia virus (HTLV-1). EBV infection may be delayed until adolescence, usually with the occurrence of infectious mononucleosis [9]. We will discuss the relationship between EBV infection and NPC initiation

Inconsistent Epidemiologic Evidence for the Etiological Role of EBV

EBV Might Only Assist in Promoting NPC Progression

Lack of a Convincing NPC Animal Model Induced by EBV Infection

Proposed Criteria to Confirm the Etiological Role of EBV in NPC

Findings

Conclusions