Human Herpesvirus 6B (HHV‑6B) is one of two closely related variants of human herpesvirus 6. This enveloped double‑stranded DNA virus belongs to the Betaherpesvirinae subfamily and primarily infects CD4 T lymphocytes, establishing lifelong latency and integrating into host telomeric DNA.
Virology and Receptor Usage
HHV‑6B has an icosahedral nucleocapsid surrounded by a tegument layer and a lipid envelope containing glycoprotein complexes. Its genome encodes a large array of proteins involved in replication, immune evasion and latency. Entry into cells is mediated predominantly through the complement regulatory protein CD46, which is broadly expressed on human cells. After fusion and delivery of the genome into the nucleus, viral replication proceeds through a cascade of immediate early, early and late gene expression, producing enlarged cells with intranuclear inclusions. Like HHV‑6A, this virus can integrate its genome into the telomeres of human chromosomes, generating a latent state that can be inherited (chromosomally integrated HHV‑6). Reactivation from latency may be triggered by immunosuppression or cellular differentiation, resulting in production of infectious virions. HHV‑6B is highly prevalent worldwide, with most people acquiring infection in early childhood.
Clinical Significance and Disease Associations
HHV‑6B is the major cause of roseola infantum (exanthem subitum), a common childhood illness characterized by high fever lasting several days followed by the sudden appearance of a maculopapular rash as the fever resolves. Febrile seizures can occur during the febrile phase. Primary infection is usually self‑limited, but HHV‑6B remains latent and can reactivate later. In immunocompromised individuals such as bone marrow or solid organ transplant recipients, reactivation may cause encephalitis, bone marrow suppression, graft rejection or delayed engraftment. HHV‑6B reactivation has also been implicated in drug‑induced hypersensitivity syndrome (DRESS). Diagnosis relies on polymerase chain reaction of blood or cerebrospinal fluid, but distinguishing latent integration from active replication may be challenging. Treatment with antiviral agents like ganciclovir or foscarnet is used for severe disease, though clinical efficacy data are limited. No vaccine is currently available, and prevention focuses on controlling reactivation in high‑risk patients. HHV‑6B is a ubiquitous betaherpesvirus that causes a characteristic pediatric exanthem and persists by integrating into host chromosomes. Its ability to reactivate and cause severe disease in immunosuppressed patients underscores the importance of awareness and monitoring in clinical practice. Related Terms: human herpesvirus 6A, roseola infantum, exanthem subitum, febrile seizure, latency