Measles immunosuppression may cause abortive, subclinical reactivation of HHV-6

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Measles immunosuppression may cause abortive, subclinical reactivation of HHV-6

Dr. Yoshizo Asano and colleagues in Japan report that in measles immunosuppression, cells sensitized to HHV-6B immediate early and early antigen proteins may suppress replication cycles and virus formation, resulting in an “incomplete” subclinical state of reactivation. In a new study, the group found that the HHV-6B lymphoproliferative response differed greatly among children suffering from acute measles compared to those with influenza patients and healthy controls, resulting in detectable HHV-6B DNA 18 of 22 subjects with measles, but not in the influenza patients or the healthy population. The authors suggest that the hypercytokinemia produced by measles infection may be the explanation.

It is known that HHV-6B specific cell-mediated immunity (CMI) can be induced in infants and young children during the traditional course of exanthema subitum. In the acute phase of exanthema subitum, NK cells seem to be crucial in the resolution of primary HHV-6B infection [Takahashi 1992; Kumagai 2006], but the role of HHV-6B specific lymphocytes in the recovery from primary infection and in the course of HHV-6B reactivation events later in life remain unknown. In a previous study, a significant antibody rise to HHV-6B was observed in several patients with acute measles, and HHV-6B was isolated in 3 of the 18 subjects analyzed (Suga 1992). Some have suggested that HHV-6B reactivation is also induced during acute measles infection, and questions remain regarding how the host CMI reaction to such reactivated virus may differ from other reactivation events.

Furthermore, measles virus infection allows replication of HHV-6B in the PBMCs of subjects and this in turn stimulates HHV-6-specific lymphocyte responses. Mobilized CMI may have suppressed viral reactivation under limited level reactivation, characterizing the combination of DNA synthesis with possibly a production of immediate-early and/or early viral proteins but without specific antibody responses or virion formation. The authors propose that this novel type of reactivation might be named “abortive” reactivation.

The present study was designed to investigate the kinetics of the lymphoproliferative response specific to HHV-6B based on three consecutive specimens from children in the first 5 weeks of acute measles. Nineteen influenza patients and nine healthy control subjects in whom immunosuppression was not present were also tested. Patients with measles showed a combined profile of HHV-6B DNA synthesis in PBMCs with a lymphoproliferative response specific to HHV-6B. Interestingly, no antibody response was detected in these cases. Thus, this study revealed the novel reactivation profile of patients with measles acting as a milder form of immunosuppression than organ transplantation.

The novel reactivation profile revealed in this study shows low HHV-6B specific lymphocyte proliferation activity during the acute phase, which increased steadily until peaking around day 16 and declining approximately 5 weeks after onset.  Conversely, lymphocyte proliferation activity to PHA increased progressively from acute to convalescent phase of measles infection. In addition, responses in lymphocyte proliferation assay to both HHV-6B and PHA did not show any statistically significant changes in activity during the observation period in either the influenza or healthy control patient group.

Taken together, the authors suggest the following:

“even under the depressed immune function resulting from measles virus infection, HHV-6B specific CMI developed in a characteristic pattern composed of elevation and waning resembling that observed in acute varicella [Kumagai et al., 1980]. This pattern might reflect the fact that HHV-6B reactivation during the course of acute measles, and the time course characteristics represent HHV-6B specific T cell mobilization to antigenic reexposure…substantiating the view that the changes in lymphocyte activities in measles patients are specifically elicited by and directed against reactivated HHV-6B.”

For more information, read the full article here.