Human herpesvirus 8 (HHV‑8), also known as Kaposi’s sarcoma‑associated herpesvirus (KSHV), is a gamma herpesvirus with a double‑stranded DNA genome. It infects endothelial cells and B lymphocytes and is the etiologic agent of Kaposi’s sarcoma and certain lymphoproliferative disorders.
Biology and Pathogenesis
HHV‑8 possesses a large double‑stranded DNA genome housed within an icosahedral capsid, enveloped by a tegument and lipid membrane studded with glycoproteins. As a member of the rhadinovirus genus, it shares structural features with Epstein‑Barr virus but has unique genes that modulate angiogenesis and cell signalling. Primary infection is thought to occur via saliva, sexual contact or blood exposure. The virus establishes latent infection in B cells and spindle‑shaped endothelial precursor cells. During latency, only a subset of viral genes are expressed, enabling infected cells to evade immune surveillance and persist. Lytic replication, triggered by inflammatory signals or immunosuppression, leads to production of new virions and expression of viral proteins that promote cell proliferation and angiogenesis. Pathogenesis and epidemiology are not fully understood, but HHV‑8 infection is more prevalent in Mediterranean, African and Middle Eastern populations and among men who have sex with men.
Disease Associations and Transmission
HHV‑8 is required for the development of Kaposi’s sarcoma, a vascular tumor characterized by spindle‑shaped cells and angiogenic lesions involving skin, mucous membranes and visceral organs. Kaposi’s sarcoma manifests in several epidemiologic forms: classic, endemic African, iatrogenic (in transplant recipients) and AIDS‑associated. The incidence is particularly high in people with advanced HIV infection, and antiretroviral therapy has markedly reduced cases. HHV‑8 is also implicated in primary effusion lymphoma, an uncommon B‑cell malignancy arising in body cavities, and in multicentric Castleman disease, a systemic lymphoproliferative disorder. Transmission occurs mainly through saliva and sexual contact; organ transplantation and blood transfusion are less common routes. Prevention involves safe sex practices and screening of organ donors. Unlike other common herpesviruses, HHV‑8 infection is not ubiquitous, and seroprevalence varies widely by region and risk group. HHV‑8/KSHV is a gamma herpesvirus that persists in latent form and reactivates under conditions of immune suppression. Its ability to manipulate host cell signalling and angiogenesis underlies the development of Kaposi’s sarcoma and related lymphoid malignancies. Related Terms: Epstein–Barr Virus, Cytomegalovirus, Human Herpesvirus 6, Human Herpesvirus 7, Varicella‑Zoster Virus