Mononucleosis pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]


Epstein-Barr virus, frequently referred to as EBV, is a member of the herpesvirus family that targets oro-pharyngeal epithelium and B cells. Transmission of the EBV through the air or blood does not normally occur. The incubation period, or the time from infection to appearance of symptoms, ranges from 4 to 6 weeks. Persons with infectious mononucleosis may be able to spread the infection to others for a period of weeks. However, no special precautions or isolation procedures are recommended, since the virus is also found frequently in the saliva of healthy people. In fact, many healthy people can carry and spread the virus intermittently for life. These people are usually the primary reservoir for person-to-person transmission. For this reason, transmission of the virus is almost impossible to prevent.


  • Following intimate contact with infected saliva, the virus infects B cells located in the oropharyngeal epithelium and subsequently spreads to involve the lymph nodes, liver and spleen.
  • Mononucleosis was so-named because the count of mononuclear leucocytes (white blood cells with a one-lobed nucleus) rises significantly.
  • There are two main types of mononuclear leucocytes: monocytes and lymphocytes.
  • Mononuclear leucocytes normally account for about 35% of all white blood cells and in patients infected with mononucleosis, this count can rise to 50-70%.
  • In addition, the total white blood count may increase to 10,000-20,000 per cubic millimeter.
  • Humoral response: As with many viral infections, such as chicken pox, antibodies to the viral antigens are developed with resultant recovery from acute illness.
  • In addition, these antibodies remain in the system for most individuals, creating a lifelong immunity to further infections.
  • Also, assessment of these specific antibodies forms the basis to diagnose mononucleosis in patients with atypical presentation or in heterophile negative cases.
  • Cellular response:
  • Is required to control the proliferation of infected B cells.
  • This in turn, helps to terminate active EBV infection and also suppress future infections with EBV.
  • Ineffective cellular response results in excessive proliferation of B cells with resultant EBV-associated malignancies such as Burkitt's lymphoma and nasopharyngeal carcinoma.


  • Transmission of EBV requires intimate contact with the saliva of an infected person.
  • Typically, the disease is transmitted from asymptomatic individuals through blood or saliva (hence the kissing disease), or by sharing a drink, or sharing eating utensils. The disease is far less contagious than is commonly thought. In rare cases, a person may have a high resistance to infection.
  • Modes of transmission include:
  • Saliva
  • Epstein-Barr virus (EBV) shed for up to 18 months after primary infection
  • Intermittent viral shedding thereafter in asymptomatic sero-positive patients
  • Increased viral shedding in immunocompromised patients
  • Blood transfusion is rare.
  • Individuals in close living arrangements nearly always pass the infection onto each other, although symptoms may not present for months or even years.

Electron Microscopy

Two Epstein-Barr virions

Microscopic Pathology

Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission. © PEIR, University of Alabama at Birmingham, Department of Pathology


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