Epstein-Barr virus: a ubiquitous pathogen Epstein-Barr virus: key features EBV infection rates and transmission Pathology of EBV infection Clinical outcomes of EBV infection Role of EBV in the development of malignancies EBV pathogenesis and serology Diagnosis of EBV infection The Panbio EBV range Further reading References

Epstein-Barr virus: a ubiquitous pathogen

EBV is a member of the herpesviridae - the only human virus in the gamma herpesvirus subfamily (Lymphocryptovirus genus) As with all herpesviruses, EBV establishes lifelong persistent infections that may undergo periodic reactivation, particularly in immunosuppressed hosts

Epstein-Barr virus: key features

Viron: Spherical, 150-200 nm diameter (icosahedral capsid, 100 nm) Genome: Circular, double-stranded DNA, ~172 kbp Subtypes: No classification system exists, however different strains have been detected with varying genome structure, antigen expression and biological properties

EBV infection rates and transmission

It is estimated that over 90% of adults are seropositive for EBV Infection usually occurs during childhood - many cases are asymptomatic The virus is transmitted primarily by saliva - transmission by blood transfusion is rare EBV is often found in the saliva of asymptomatic people

Pathology of EBV infection

Click to view diagram EBV also infects epithelial cells, but the significance of this is unknown - B cells are thought to be the mediator of primary and persistent infection

Clinical outcomes of EBV infection

Infectious mononucleosis When infection with EBV occurs during adolescence or early adulthood, there is a 35-50% chance that infectious mononucleosis ("glandular fever") will develop after an incubation period of 4-6 weeks Common symptoms Fever Sore throat Lymphadenopathy Uncommon symptoms Splenomgaly Rare complications Hepatitis Myocarditis Thrombocytopenia Fatal complications In males with an XLP gene, infectious mononucleosis can be fatal due to liver failure

Role of EBV in the development of malignancies

EBV is linked to the development of several malignant tumours, including B cell neoplasms such as Burkitt's lymphoma, Hodgkin's disease, some forms of T cell lymphoma, undifferentiated nasopharyngeal carcinoma and a proportion of gastric cancers Burkitt's lymphoma Burkitt's lymphoma is a rare cancer of the jaw, first described in East African children and young adults Tumours in > 90% of African sufferers contain EBV DNA and EBNA antigen, compared with 20% of sufferers elsewhere It is thought that EBV plays a causative role in early stages by immortalizing B cells, but it is not known how Burkitt's lymphoma cells escape elimination by the immune system Lymphoproliferative diseases in immunosuppressed hosts Immunodeficient patients - e.g. AIDS, post-transplant - are susceptible to EBV-induced lymphoproliferative diseases, including lymphomas (diffuse polyclonal), lymphocytic interstitial pneumonitis and hairy oral leukoplakia of the tongue Post-transplant lymphoproliferative disorder: Following organ transplantation, immunosuppressive therapy can promote the expansion of EBV-infected T cells Is EBV involved in the development of multiple sclerosis? A recent study suggests a relationship between EBV infection and development of MS(2): Blood samples were collected from over 3 million US military personnel The 83 patients who developed MS had significantly higher levels of EBV VCA IgG and EBNA antibodies

EBV pathogenesis and serology

Following primary infection with EBV, antibodies to a number of viral antigens appear in the bloodstream Viral capsid antigen (VCA) is the primary marker used for the diagnosis of EBV infection VCA IgM appears within the first week of infection and remains detectable for up to three months VCA IgG appears within 4-7 days after onset of symptoms and may persist for life Epstein-Barr nuclear antigen (EBNA) IgM antibodies are detectable 3-6 days after onset of symptoms, often appearing before VCA IgM EBNA IgG antibodies mark the transition from acute infection to convalescence and may persist for life Early antigen diffuse (EA-D) IgG antibodies peak at three weeks and decline to undetectable levels by three months

Diagnosis of EBV infection

Susceptibility: If EBNA IgG antibodies are not found, the patient is susceptible to EBV infection Primary infection: VCA IgM present, EBNA IgG absent Rising or high VCA IgG - antibodies appear 4-7 days after onset of symptoms 80% of patients with active EBV infection produce EA-D IgG - levels peak at three weeks Past infection: EBNA IgG antibodies indicate past infection In the absence of VCA IgM, VCA IgG may also be a marker of past infection Reactivation: EBNA IgG and elevated EA-D IgG antibodies suggest reactivated infection VCA IgM may also be present EBV reactivation is not associated with a clearly defined clinical syndrome Chronic EBV infection: Reliable lab evidence is seldom found in patients with symptoms of four months duration or more

The Panbio EBV range

The Panbio EBV range: superior sensitivity and specificity ELISA EBV VCA IgG ELISA EBV VCA-p18 IgG ELISA EBV VCA IgM ELISA EBNA IgG ELISA EBNA IgM ELISA* IFA EBV VCA IgG IFA EBV VCA IgM IFA* EBNA ACIF*

Further reading

We hope this site has provided you with a good overview of Esptein-Barr virus.  Please follow the links below for further information or contact Panbio. CDC website EBV & IM Virology Down Under

References

1. Murray PG and Young LS. Expert Reviews in Molecular Medicine 2001.  2. Levin LI et al. JAMA 2003; 289: 1533-36 * Not available for sale or distribution in the USA.