Abstract
Epstein–Barr virus (EBV) is a human γ-herpesvirus that infects up to 95% of the adult population. Primary EBV infection usually occurs during childhood and is generally asymptomatic, though the virus can cause infectious mononucleosis in 35–50% of the cases when infection occurs later in life. EBV infects mainly B-cells and epithelial cells, establishing latency in resting memory B-cells and possibly also in epithelial cells. EBV is recognized as an oncogenic virus but in immunocompetent hosts, EBV reactivation is controlled by the immune response preventing transformation in vivo. Under immunosuppression, regardless of the cause, the immune system can lose control of EBV replication, which may result in the appearance of neoplasms. The primary malignancies related to EBV are B-cell lymphomas and nasopharyngeal carcinoma, which reflects the primary cell targets of viral infection in vivo. Although a number of antivirals were proven to inhibit EBV replication in vitro, they had limited success in the clinic and to date no antiviral drug has been approved for the treatment of EBV infections. We review here the antiviral drugs that have been evaluated in the clinic to treat EBV infections and discuss novel molecules with anti-EBV activity under investigation as well as new strategies to treat EBV-related diseases.
Highlights
The human γ-herpesviruses Epstein–Barr virus (EBV or human herpesvirus 4, HHV-4) is one of the most commonly contracted herpesvirus, infecting up to 95% of the adult human population.Primary EBV infection generally occurs during childhood and is usually asymptomatic
We review here the antiviral drugs that have been evaluated in the clinic to treat EBV infections and discuss novel molecules with anti-EBV activity under investigation as well as new strategies to treat EBV-related diseases
The symptoms of infectious mononucleosis typically subside in 1 to 2 months, the rates of chronic fatigue symptoms in adolescents following resolution of infectious mononucleosis are of 13%, 7%, and 4%, at 6, 12, and 24 months, respectively [1]
Summary
The human γ-herpesviruses Epstein–Barr virus (EBV or human herpesvirus 4, HHV-4) is one of the most commonly contracted herpesvirus, infecting up to 95% of the adult human population. Based on the expression of latent genes, EBV latency is classified in different types (Figure 2A) [7]. Cellular genetic alterations and/or co-infections occur in EBV-associated malignancies (Figure 2B). The cellular genetic alterations and/or co-infections are known to occur in the expressed in the type III latency. (b) The cellular genetic alterations and/or co-infections are known to different types of EBV-associated malignancies. PEL: primary effusion lymphoma; HL: Hodgkin occur in the different types of EBV-associated malignancies. Maybe the most important reason for the failure of antivirals for infectious mononucleosis therapy can be ascribed to the fact that the symptoms and signs of the disease are not the consequences of viral replication but the immunological response to EBV-infected B-cells that circulate in the blood and infiltrate the tissues of different organs. Double-blind, placebo controlled study, prednisolone administered with acyclovir for treatment of infectious mononucleosis inhibited oropharyngeal EBV replication without affecting duration of clinical symptoms or development of EBV-specific cellular immunity [16]
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