Viral antigen expression in individuals with chromosomal integrated HHV6

Abstract number: O504

Strenger V., Schwinger W., Zenz W., Lautenschlager I., Aberle S.W., Popow-Kraupp T., Nacheva E.P., Virgili A., Zobel G., Urban C.

Objectives: Chromosomal integration of the HHV-6 genome (CIHHV-6) into the human genome occurs in 1–2% of healthy individuals and leads to persistently high levels of HHV-6 PCR copy numbers in blood and tissue. Consequently, this may be interpreted as persistent active HHV-6 infection.

Although HHV-6 mRNA has been detected in a few individuals with CIHHV-6, there is no evidence of replication of viral particles up to now. Viral cultures have shown negative results. So, CIHHV-6 is thought not to be linked to any disease.

Methods: We performed HHV-6 antigen detection in PBMCs of 4 individuals with FISH proven CIHHV-6 by means of antibodies directed against HHV-6 variant A and B (indirect immunoperoxidase staining).

Results: In 2 unrelated female adolescents (both with CIHHV-6 variant A) we detected HHV-6 antigen. One patient is suffering from recurrent parotitis since 5 years and from hypoimmunoglobulinaemia. The other patient (15a) was treated with allogeneic bone marrow transplantation (BMT) for acute myeloid leukaemia (AML) and acquired CIHHV-6 from the healthy donor. So, CIHHV-6 is only found in blood cells. In the latter patient only symptoms attributable to the post BMT course have been observed (prolonged mixed haematological chimerism, protracted mucositis, transient hypertension and transient neuropathy). At the time of antigen detection 5 years after BMT the patient was clinically well.

In 2 individuals (a girl after fatal myocarditis and her healthy father – both with variant B) no HHV-6 antigen has been detected.

Discussion: Up to now CIHHV-6 is considered not to cause any disease. For the first time we show the expression of HHV-6 antigen, which indicates the replication of viral particles. This might have a pathophysiological impact.

One patient with positive antigen detection is suffering from a disease of unclear aetiology. So, an association of replication of CIHHV-6 with the disease might be considered.

In contrast, the other patient did not show any symptoms at the time of antigen detection. This patient shows a special mode of acquisition of CIHHV-6 (by BMT) possibly resulting in differences in the immunological priming and response. In addition, in the latter patient CIHHV-6 is restricted to blood cells.

Two other patients did not show antigen expression. So, it is unclear how the transcription and translation of viral genes is influenced?

Furthermore, is there a pathophysiological impact of viral replication in individuals with CIHHV-6?