Elucidation of the Cross-Reactive Immunoglobulin M Response to Human Herpesviruses 6 and 7 on the Basis of Neutralizing Antibodies

Human herpesvirus 6 (HHV-6) is closely related to HHV-7 in terms of genome organization and sequence. The cross-reactive responses between HHV-6 and HHV-7 have been reported by using immunofluorescent techniques. Recently we have shown that neutralizing (NT) antibody responses are specific to each virus and do not cross-react. We took advantage of this and used the NT antibody response to estimate the time of seroconversion to each virus and examined the pattern of humoral immune response, especially the immunoglobulin M (IgM) response, against each virus antigen in the natural course of infection with HHV-6 and HHV-7. In children who experienced HHV-6 infection first, followed by HHV-7 infection, the IgM response at the first HHV-6 infection was directed only against HHV-6, while no IgM response was directed against HHV-7 at the second HHV-7 infection. In contrast, in children who experienced HHV-7 infection first, followed by HHV-6 infection, the IgM response at the first HHV-7 infection was directed not only against HHV-7 but also against HHV-6. These data suggest that cross-reactive responses to heterologous viruses should be taken into consideration when making a diagnosis based on IgM antibody

Neutralizing Antibody Responses to Human Herpesviruses 6 and 7 Do Not Cross-React with Each Other, and Maternal Neutralizing Antibodies Contribute to Sequential Infection with These Viruses in Childhood

Seroprevalence of human herpesvirus 6 (HHV-6) and HHV-7 infections is very high throughout the world, and almost all people are exposed first to HHV-6 and second to HHV-7 in their childhood. However, it is not clear whether the neutralizing (NT) antibody response between each virus is cross-reactive or not. To elucidate the NT antibody response between each virus, 55 serum samples from an adult group (subjects 22 to 88 years old) and 60 serum samples from a young group (subjects 2 to 18 years old) were examined by a dot blot method for detecting viral late antigen. Thirty-nine serum samples obtained from cord bloods and a few serum samples obtained from pediatric patients with exanthem subitum were also examined to assess the maternal transferred NT antibodies against each virus. The NT antibody titers against HHV-7 in the adult group remained high throughout all the individuals, and none were negative. Those against HHV-6 were high values in the young group but low values, including negative values (three samples), in the adult group. These results suggested that the NT antibody response to either HHV-6 or HHV-7 in each individual was specific to each virus and did not cross-react with each other. In the adult group, the NT antibody response to HHV-6 decreased, while that to HHV-7 remained high throughout all the individuals. Maternal transferred NT antibody titers against HHV-7 were higher and remained longer after birth than those of HHV-6, and these findings were in accord with the clinical observation that HHV-6 infection usually occurs earlier than HHV-7 infection