Epstein-Barr virus

The Epstein-Barr virus (EBV) or HHV4 is a herpesvirus. It infects 90% of adults worldwide.

Age of infection
Typically child who acquire EBV are symptomatic. In adolescents and young adults, EBV can cause the symptoms of mononucleosis.

Later age of infection has been associated with increased risk of multiple sclerosis.

Latency
In most adults, the virus remains latent for life in B cells. It is estimated that 1 in every one hundred thousand to one million circulating B cells carry EBV. In healthy hosts, EBV populations are kept in check by CD4+ and CD8+ T-cell responses.

The equilibrium can be disrupted in individuals with compromised immune systems such as patients with AIDS or transplant patients taking immune system suppressing drugs. It has been observed that these patients are more susceptible to EBV-related cancers, such as certain lymphomas and carcinomas.

Natural killer T cells
It is thought that natural killer T cells (NKT) play a pivotal role in the control of EBV-infected B cells through their recognition of CD1d expressing cells.

Neuronal infection
A 2015 study demonstrated that human neoronal cells could be directly and actively infected with EBV and another herpesvirus, Kaposi's sarcoma-associated herpesvirus (KSHV).

Neuronal cells were infected with EBV or KSHV viruses which had been combined with a fluorescent protein so that the infection could be observed. The infection was seen to produce new virus cells (productive) and spread efficiently. Significantly, it not only infected surrounding neuronal cells but also nearby peripheral blood mononuclear cells.

Acyclovir, an antiviral drug which inhibits (but does not destroy) herpesviruses, was shown to also inhibit the virus production. This suggests that EBV replicates via lytic replication.

EBV is known to be linked to many neuronal diseases but this is the first evidence of how this may occur. The researchers note that this research supports the presence of EBV in neuronal diseases, but does not indicate why this is so.

In human disease
Epstein-Barr virus may play a role in a wide number of diseases including Chronic fatigue syndrome, multiple sclerosis, and myasthenia gravis.

Chronic fatigue syndrome
A prospective study of 250 primary care patients revealed a higher prevalence of chronic fatigue syndrome after infectious mononucleosis (glandular fever) when compared to an ordinary upper respiratory tract infection. Anti-early antigen titers to EBV were elevated in CFS patients and associated with worse symptoms.

Multiple sclerosis
Infection later in life, high serum titers against EBV, and mononucleosis have all been associated with an increased risk of multiple sclerosis. MS relapses are correlated with EBV reactivation.

Myasthenia gravis
Autoantibodies to acetylcholine receptors, alpha subunit have been found in patients with myasthenia gravis. These cross react with herpesvirus glycoprotein D. Antibodies to acetylcholine receptor and HSV-1 antigens crossreact.

B cells from myasthenia gravis patient stimulated in vitro by Epstein-Barr virus produced acetylcholine autoantibodies. Ongoing EBV infection of the thymus has been posited as a causative agent for the production of aceytlcholine receptor autoantibodies in myasthenia gravis.

Lyme Disease
Several herpesviruses including Epstein-Barr virus may cause false positives on Lyme Disease tests.

Vitamin D
Some recent research is finding links between EBV and Vitamin D

An Epstein barr virus protein EBNA-3 has an affinity for VDR and may actually block the activation of VDR-dependent genes by Vitamin D.

Vitamin D receptor may be required for the normal development of natural killer T cells that react to cells expressing CD1d, as in cells infected by EBV.

As low Vitamin D is also a risk factor for MS, some studies have attempt to find a link between low Vitamin D status, EBV and MS. One study of healthy individuals found no link between EBV load and Vitamin D status. However, over half the subjects were Vitamin D deficient and none had optimal levels (i.e., above 100 nmol/l)

Treatment
Epstein-barr is thought to persistent harmlessly in immunocompetent individuals but in those with compromised immune systems has been associated with certain cancers and possibly autoimmune disease.

Several antivirals are active against EBV including valganciclovir and spironolactone.

A theoretical immunotherapy treatment proposes that inducing CD1d expression on EBV-infected B cells could prompt effective immune suppression of EBV by NKT cells.