Human herpesvirus 6B (HHV‑6B) is a double‑stranded DNA virus in the Roseolovirus genus of the Betaherpesvirinae subfamily. It is the primary cause of exanthem subitum (roseola infantum) and can establish lifelong latency.
Biology and Pathogenesis
HHV‑6B has a double‑stranded DNA genome packaged in an icosahedral capsid, surrounded by a tegument and a lipid envelope bearing glycoproteins. Primary infection usually occurs in early childhood through exposure to saliva. The virus replicates in T lymphocytes, monocytes, epithelial cells, neurons and glia. Studies show that HHV‑6B, like HHV‑6A, can infect glutamatergic and dopaminergic neurons and glial cells but not GABAergic neurons. Its replication produces relatively mild cytopathic effects compared with HHV‑6A. HHV‑6B infection induces proinflammatory cytokines such as tumor necrosis factor‑alpha. After the initial illness, HHV‑6B persists in a latent state in mononuclear cells and can integrate into chromosomal telomeres. Reactivation may occur during immunosuppression and is associated with disease in transplant recipients. Serologic surveys indicate that nearly all humans are infected by five years of age. Host immunity, particularly cell‑mediated responses, controls viral replication but does not eliminate latent virus.
Clinical Significance and Research
HHV‑6B is best known as the etiologic agent of roseola infantum, a common childhood illness characterized by high fever lasting three to five days followed by a maculopapular rash as the fever subsides. Febrile seizures are a frequent complication of HHV‑6B infection in infants. The virus can cause encephalitis in immunocompromised individuals and has been implicated in limbic encephalitis after hematopoietic stem cell transplantation. Reactivation of HHV‑6B in transplant recipients can contribute to graft rejection and delayed engraftment. Studies comparing HHV‑6A and HHV‑6B reveal differences in cytokine induction and cytopathic effects; HHV‑6B tends to increase tumor necrosis factor‑alpha without triggering the Toll‑like receptor 9 and interleukin 10 pathway seen with HHV‑6A. Both viruses can infect neurons and glial cells, emphasising their neurotropic potential. Ongoing research aims to clarify the role of HHV‑6B in epilepsy, multiple sclerosis and other neurologic conditions. HHV‑6B is a ubiquitous roseolovirus that causes roseola and establishes lifelong latency; reactivation can lead to serious complications in immunocompromised hosts. Awareness of its clinical spectrum and differences from HHV‑6A is important for diagnosis and management. Related Terms: Human Herpesvirus 6A, Human Herpesvirus 7, Cytomegalovirus, Epstein–Barr Virus, Varicella‑Zoster Virus