Expression of Human Herpesvirus-6 Antigens in Benign and Malignant Lymphoproliferative Diseases

Abstract

Immunohistochemistry was used to look for the expression of human herpesvirus-6 (HHV-6) antigens in a well characterized series of benign , atypical, and malignant lymphoid lesions , which tested positive for the presence of HHV-6 DNA. A panel of specific antibodies against HHV-6 antigens , characteristic either of the early (p41) or late (p101K , gp106, and gp116) phases of the viral cycle , was applied to the lymphoid tissues from 15 non-Hodgkin's lymphomas , 14 Hodgkin's disease cases , 5 angioimmunoblastic lymphadenopathies with dysproteinemia , 14 reactive lymphadenopathies , and 2 cases of sinus histiocytosis with massive lymphadenopathy (RosaiDorfman disease). In lymphomatous tissues , the expression of late antigens was documented only in reactive cells , and mainly in plasma cells. Of interest, the expression of the early p41 antigen was detected in the so-called "mummified" Reed-Sternberg cells, in two Hodgkin's disease cases. In reactive lymphadenopathies , the HHV-6 late antigen-expressing cells were plasma cells , histiocytes , and rare granulocytes distributed in interfollicular areas. In both cases of Rosai-Dorfman disease , the p101K showed an intense staining in follicular dendritic cells of germinal centers , whereas the gp106 exhibited an intense cytoplasmic reaction in the abnormal histiocytes , which represent the histological hallmark of the disease.

Anatomical mapping of human herpesvirus reservoirs of infection

“…41 Disseminated infection may be associated with hepatitis, pneumonia, marrow suppression, and encephalitis. HHV-6 has also been detected, albeit at low levels, in Hodgkin's lymphoma and angioimmunoblastic lymphadenopathy, 42 and has been implicated in multiple sclerosis. 43 HHV-6 infection is common in early childhood, when it presents as a febrile illness with rash, known as roseola.…”

Intrathoracic Rosai-Dorfman Disease with Spontaneous Remission: A Clinical Report and a Review of the Literature

“…IgG antibody for Epstein-Barr virus (EBV)-viral capsid antigen and EBV-nuclear antigen, and IgM antibody for HHV-6 were negative and IgG antibody for HHV-6 was positive in the present case. In addition, HHV-6-specific DNA was detected within the histiocytes from RDD patients in 7 out of 9 cases by in situ DNA hybridization (Luppi et al 1998). The current patient had a previous infection of HHV-6.…”

Human herpesvirus-6-associated acute lymphadenitis in immunocompetent adults

“…10 Initially, the atypical cytological features of the virally infected cells raised the possibility of involvement by non-Hodgkin's lymphoma with immunoblastic features. However, the lack of an aberrant phenotype and absence of evidence of a clonal T-cell process did not support this diagnosis.…”

“…Immunohistochemical studies 10 showed that HHV-6-positive cells in cases of reactive lymphadenopathy are plasma cells, histiocytes, and rare granulocytes. In vitro studies have shown that HHV-6 replicates and induces cytopathic effects in CD4 þ -positive T lymphocytes, but it has been also shown to be tropic for other cells including CD8…”