Evidence for a recessive major gene predisposing to human herpesvirus 8 (HHV-8) infection in a population in which HHV-8 is endemic

Abstract

Infection by human herpesvirus 8 (HHV-8), as measured by the presence of specific antibodies, was shown in countries in which HHV-8 infection is endemic to exhibit familial aggregation and a peculiar variation with age (rapid increase until puberty followed by a plateau in young adults). To investigate whether host genetic factors could explain these findings, a segregation analysis was performed of 81 families of African origin (1623 subjects; HHV-8 seroprevalence, 11.9%) living in a village in French Guiana in which HHV-8 infection is endemic. Results provide evidence for a recessive gene controlling susceptibility or resistance to HHV-8 infection. This gene is predicted to have a major effect during childhood, with almost all homozygous predisposed subjects (∼6% of the population) being infected by age 15. For nonpredisposed subjects, HHV-8 infection in childhood strongly depends on virus exposure (through an HHV-8-infected mother), whereas the risk of infection appears to be low in young adults, with no evidence for heterosexual transmission.