Epstein–Barr Virus Epidemiology, Serology, and Genetic Variability of LMP-1 Oncogene Among Healthy Population: An Update

Abstract

The Epstein–Barr virus (EBV) is a DNA lymphotropic herpesvirus and the causative agent of infectious mononucleosis. EBV is highly prevalent since it affects more than 90% of individuals worldwide and has been linked to several malignancies including PTLDs, which are one of the most common malignancies following transplantation. Among all the EBV genes, most of the recent investigations focused on studying the LMP-1 oncogene because of its high degree of polymorphism and association with tumorigenic activity. There are two main EBV genotypes, Type 1 and 2, distinguished by the differences in the EBNA-2 gene. Further sub genotyping can be characterized by analyzing the LMP-1 gene variation. The virus primarily transmits through oral secretions and persists as a latent infection in human B-cells. However, it can be transmitted through organ transplantations and blood transfusions. In addition, symptoms of EBV infection are not distinguishable from other viral infections, and therefore, it remains questionable whether there is a need to screen for EBV prior to blood transfusion. Although the process of leukoreduction decreases the viral copies present in the leukocytes, it does not eliminate the risk of EBV transmission through blood products. Here, we provide a review of the EBV epidemiology and the genetic variability of the oncogene LMP-1. Then, we underscore the findings of recent EBV seroprevalence and viremia studies among blood donors as a highly prevalent transfusion transmissible oncovirus.

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“…There are two main EBV genotypes, type 1 and type 2, distinguished by the differences in EBNA‐2 gene, which can further be subdivided into different virus strains . Type 1 is prevalent in population from Europe, America, China and South Asia, while type 2 is more observed in African and Papua New Guinean populations, where it shares an equal distribution with type 1.…”

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“…In some cases, EA (D) IgG is detectable several years after a primary infection. High titers of EA (D) IgG, VCA and EA IgA have been observed in patients with NPC [44][45][46].…”

“…However, only a few have generally been investigated and utilized for diagnostic purposes [9]. It has been shown that anti-EA antibodies (EA immunoglobulin G (IgG)) are of two forms; EA-diffuse (D) IgG, which increases within three-to-four weeks and could remain until three-to-four months, and EA-restricted (R) IgG, which may remain at a high level for up to two years [9,44]. In some cases, EA (D) IgG is detectable several years after a primary infection.…”

“…In certain cases of protracted disease, EA (R) IgG remains detectable following the waning of EA (D) IgG, as seen in patients below two years old, Burkitt lymphoma patients, and recently infected patients. Both types of EA, (D) and (R), have also been observed in immunocompromised patients and in cases of reactivation [44,45,47]. Though antibodies against VCA IgG and immunoglobulin M (IgM) commonly appear at the time when patients show clinical symptoms of acute infection, IgG remains positive throughout the patients' lives, while IgM disappears within a few weeks, though the levels may persist for several months [48].…”

“…To date, ISH, RNA, and protein-based assays, quantitative real-time polymerase chain reaction (qPCR) and immunoblotting have been utilized in the diagnosis of EBV and in determining the stage of infection [65]. Though these methods help in diagnosis, due to the absence of standardization, the differences in sensitivity and specificity observed among laboratories ought to be systematically considered [9,44,65]. In addition to investigating other serological markers, more recent investigations have demonstrated that qPCR is an imperative technique, especially for the diagnosis of EBV acute infection and silent reactivation, because it is considered sensitive, reliable, stringent, simple, specific, precise, and fast [9].…”