Infectious mononucleosis is a condition common among young adults and characterized by symptoms such as fatigue, fever, sore throat, rash, liver dysfunction, presentation of atypical lymphocytes, and lymphadenopathy. Although many cases of infectious mononucleosis are caused by Epstein-Barr virus (EBV), a subset (approximately 5%) are caused by HHV-6 (Naito 2006, Akashi 1993). Cases of mononucleosis-like syndrome associated with HHV-6 infection have also been reported in response to the administration of drugs known to reactivate HHV-6 (Tomita 2002).

Studies have shown that active HHV-6 infection is significantly associated with general lymphadenitis/lymphadenopathy. Histological features associated with HHV-6B lymphadenitis have been described using tissue biopsy, and demonstrate that CD4+ T Lymphocytes are the cells affected during the course of infection (Maric 2004). One study from Brazil indicates that nearly 25% of lymphadenopathy cases are positive for HHV-6 IgM antibodies, and all of these cases were positive for HHV-6A DNA, suggesting a role for HHV-6A in the condition as well (Freitas 2003). Of note, HHV-6 is occasionally detected in tissue samples from patients with Rosai-Dorfman disease (RDD), a rare disorder characterized by the presence of histiocytes in lymph nodes throughout the body (Arakaki 2012).

In addition to the association between HHV-6 and lymphadenopathy/lymphadenitis, HHV-6 is known to directly infect lymphatic epithelial cells. For more information, visit our page on HHV-6 & Endothelial Cell Dysfunction/Arteriopathies.

Key Papers: HHV-6 & Mononucleosis/Lymphadenopathy


Naito 2006 Causes of infectious mononucleosis-like syndrome in adult patients.
Tomita 2002 [Two cases of infectious mononucleosis-like syndrome associated with human herpes-virus 6].
Akashi 1993 Brief report: severe infectious mononucleosis-like syndrome and primary human herpesvirus 6 infection in an adult.


Bai 2014 HHV-6-associated acute lymphadenitis in immunocompetent patients: a case report and review of literature
Descamps 2013 DRESS symptoms and thyroiditis: HHV-6, the possible common link
Arakaki 2012 Rosai-Dorfman disease: renal involvement with HHV-6 detection. Description of a case report.
Maric 2004 Human herpesvirus-6-associated acute lymphadenitis in immunocompetent adults.
Freitas 2003 Evidence of active herpesvirus 6 (variant-A) infection in patients with lymphadenopathy in Belém, Pará, Brazil.
Caruso 2009 U94 of human herpesvirus 6 inhibits in vitro angiogenesis and lymphangiogenesis.