Clinical impact of primary infection with roseoloviruses

•HHV-6B primary infection occurs in nearly all children by three years of age.•HHV-6 can integrate into the host genome and be passed via germline transmission.•Only a quarter of HHV-6B primary infections manifest as roseola infantum in the US.•HHV-6B or HHV-7 account for 1/3 of febrile status epilepticus cases in children.•Delayed HHV-7 primary infection may be associated with more severe neurologic complications.

The roseoloviruses, human herpesvirus-6A -6B and -7 (HHV-6A, HHV-6B and HHV-7) cause acute infection, establish latency, and in the case of HHV-6A and HHV-6B, whole virus can integrate into the host chromosome. Primary infection with HHV-6B occurs in nearly all children and was first linked to the clinical syndrome roseola infantum. However, roseolovirus infection results in a spectrum of clinical disease, ranging from asymptomatic infection to acute febrile illnesses with severe neurologic complications and accounts for a significant portion of healthcare utilization by young children. Recent advances have underscored the association of HHV-6B and HHV-7 primary infection with febrile status epilepticus as well as the role of reactivation of latent infection in encephalitis following cord blood stem cell transplantation.