T-cell dysfunction and resulting insufficient control of EBV infection is common to all these patients in whom EBV-associated lymphoproliferations develop. EBV is an oncogenic virus which induces proliferation and transformation of B-lymphocytes. Antiviral treatment may represent a causal treatment option with relatively low toxicity.
Gather up your favorite movies or shows for a binge-watching session. Ask your family and friends for help with meals and other household tasks.
Almost everyone gets a case of the Epstein-Barr virus at some time in their lives. Most of these cases are asymptomatic. The most critical time of life to be mindful of catching this virus is during the college years. By reducing risk of exposure, young adults can avoid missing school or work for weeks due to infectious mononucleosis. Thankfully, if you are exposed and develop mono, you have a good chance of recovering fully within several weeks.
Sign up for our Health Tip of the Day newsletter, and receive daily tips that will help you live your healthiest life. American Family Physician. Common questions about infectious mononucleosis. March 15, Centers for Disease Control. About mono infectious mononucleosis Updated September 28, Immunization with components of the viral fusion apparatus elicits antibodies that neutralize Epstein-Barr virus in B cells and epithelial cells.
Vaccination against the Epstein—Barr virus. Cell Mol Life Sci. Kimura H, Cohen JI. Chronic active Epstein-Barr virus disease. Front Immunol. How I treat T-cell chronic active Epstein-Barr virus disease. Actively scan device characteristics for identification. Use precise geolocation data. Select personalised content.
Create a personalised content profile. Measure ad performance. Select basic ads. EBV is a herpes virus that can cause infectious mononucleosis and can exist in its host as a latent infection for the rest of their lives.
However, pinpointing the causal relationship between EBV and MS has posed problems due to inconclusive results from prior analysis of population data. During the study, the investigators included 10 million young adults on active duty in the US military in their analysis. Based on analyses of serum samples conducted biennially by the US military, the investigators were able to determine the EBV status of soldiers based on the results of their samples. Epstein—Barr virus is also associated with several B-cell malignancies including Burkitt lymphoma, Hodgkin lymphoma, and post-transplant lymphoproliferative disease.
A number of antiviral drugs have proven to be effective inhibitors of EBV replication, yet have resulted in limited success clinically, and none of them has been approved for treatment of EBV infections. Why is it that despite the profusion of drugs developed through the years that inhibit replication of the Epstein—Barr virus EBV their use clinically has been limited? The problem is illustrated by the commonest infection caused by EBV in Western countries: infectious mononucleosis IM.
First, its onset is insidious with nondescript sore throat, swollen lymph nodes, and splenic enlargement, along with lassitude that persists up to six months or longer while the virus has already been actively replicating for some time and shed from the oropharyngeal epithelial cells. Consequently, drugs given largely post-facto are too late. Infectious mononucleosis is essentially an immunologic condition triggered by EBV that is signaled by the atypical T-cell response in the blood.
It therefore can be imagined that combined treatment with antiviral and immunosuppressive drugs might have an impact on infectious mononucleosis. However, in trials in which corticosteroid and antiviral drugs were administered together, the effects were marginal [ 1 ]. Acyclovir ACV was shown in to check replication of the virus with essentially no toxicity [ 2 ] because it selectively inhibited viral but not cellular replication.
Its antiviral effective dose ED 50 was established as 0. Acyclovir triphosphate is incorporated into the viral DNA where it forms a tight dead-end complex that stops irreversibly its chain elongation. It however can be valuable when used selectively. However, neither acyclovir nor other drugs have any effect on latent infection, which is dependent upon persistent EBV episomes, the circular form of EBV genome, not the encapsulated linear form [ 4 ].
The episome is replicated by the same mechanisms used by cells once every cell cycle, maintaining a stable number through successive generations. It is not itself oncogenic, but serves as the molecular basis of the latent state of EBV infection [ 5 ]. No inhibitors of EBV latent infection have materialized over the decades. Accordingly, despite prolonged suppression of viral replication, some latently infected cells will persist and will restore the population of the latent cells.
At the same time, non-toxic antiviral drugs are indispensable for treatment, and potentially prophylaxis, of infection in inborn and acquired immunodeficiency syndromes in which the latent genome has been reactivated. In the immunocompetent, there is initially runaway B-cell proliferation, but it is normally checked by efficient T-cell responses. Acyclovir is a nucleoside analog as are penciclovir, ganciclovir, and their oral prodrugs. In addition to its subtle onset, IM has a long incubation time 4—6 weeks , which results in late diagnosis in contrast to infections caused by HSV or VZV.
Thus, the difficulty in the diagnosis of IM may be in part responsible for the lack of success in the development of a generally useful antiviral agent for EBV infection, except in immunodeficient states when there is active viral replication.
Diagnostically, IM is characterized by atypical T-cell lymphocytosis that results from the massive cell-mediated immune response against EBV-infected B-lymphocytes. Thus, it has been suggested that antivirals in combination with immunomodulatory drugs such as corticosteroids, used empirically by physicians to treat IM might be beneficial.
However, in a multicenter, double-blind, placebo-controlled trial, prednisolone administered with ACV for treatment of IM inhibited oropharyngeal EBV replication without affecting the duration of clinical symptoms or development of EBV-specific cellular immunity [ 1 , 7 ]. The hepatitis associated with IM has been shown to be accompanied by a high viral burden [ 8 , 9 ], and accordingly specific antivirals could possibly alleviate symptoms of this common EBV-related complication, which is in any case, almost always benign and self-limiting.
Chronic active EBV infection is rare. It is unrelated to the fatigue experienced in IM that may last months to a year. Post-transplant lymphoproliferative disease is a potentially fatal complication following stem cell and solid organ transplantation. Late-onset lymphomas occurring after the first year are less likely to be associated with EBV [ 14 ].
IL-6 plays a crucial role in the maintenance of immune responses. In , Malouf and colleagues [ 12 ] reported a reduction in the incidence of PTLD in lung and heart-lung transplant recipients who received antiviral prophylaxis.
They analyzed its incidence before and compared the impact of long-term antiviral prophylaxis on the development of PTLD in EBV-seronegative recipients between and There was a significantly lower EBV viral load depending on the type and intensity of the immunosuppressive therapy.
In a retrospective cohort study, the impact of antiviral prophylaxis given to prevent human cytomegalovirus HCMV disease in 73 EBV-seronegative adult kidney recipients on early and late PTLD onset was analyzed [ 16 ]. Epstein—Barr virus PCR monitoring revealed that prophylaxis delayed primary infection at days, but early PTLD incidence was not different between groups.
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