Betaherpesviruses

Betaherpesvirinae is a subfamily of the Herpesviridae family. Members are enveloped, double-stranded DNA viruses characterized by slow replication and a strong tendency to establish long-lasting latent infections in hematopoietic cells. The subfamily comprises four genera: Cytomegalovirus, Muromegalovirus, Roseolovirus, and Proboscivirus.

Human-infecting members include cytomegalovirus (CMV, HHV-5) of the Cytomegalovirus genus and the roseoloviruses HHV-6 and HHV-7 in the Roseolovirus genus. The Muromegalovirus genus contains murine CMV, and Proboscivirus includes elephant endotheliotropic herpesviruses. Betaherpesviruses have large genomes and a broad host range across mammals, with pathogenic potential varying by host species and immune status.

Biology and latency are hallmarks of betaherpesviruses. They replicate slowly and establish latency in cells of the immune system, particularly monocytes and bone marrow–derived progenitors. Reactivation can occur during immunosuppression or other stress, releasing infectious virus. Transmission routes differ by virus but commonly include bodily fluids for human CMV; congenital infection is a major concern for CMV.

Clinical significance varies by virus and host. Human CMV is a major cause of congenital infection and can cause sensorineural hearing loss and neurodevelopmental issues; in immunocompromised individuals, CMV reactivation can lead to retinitis, colitis, pneumonitis, or graft failure after transplantation. Roseoloviruses HHV-6 and HHV-7 cause roseola infantum in children and have been linked to various neurologic manifestations in some settings. EEHV, a Proboscivirus member, primarily affects elephants and can be fatal.

Diagnosis relies on serology and nucleic acid testing (PCR) to detect viral DNA, alongside clinical assessment. Antiviral therapy includes ganciclovir or valganciclovir, cidofovir, and foscarnet for CMV disease or immunocompromised patients. No widely licensed vaccine exists, though several candidates are in development.