Human Herpesvirus 8 (HHV-8), also known as Kaposi’s Sarcoma-associated Herpesvirus (KSHV), is a DNA virus belonging to the Herpesviridae family. It is an oncogenic virus, meaning it can contribute to the development of certain cancers in humans. First identified in 1994, HHV-8 has since been linked to several significant diseases, particularly in individuals with weakened immune systems. Its prevalence varies globally.
Understanding HSV-8
Human Herpesvirus 8 is classified within the Gammaherpesvirinae subfamily of DNA viruses. Like other herpesviruses, HHV-8 has a biphasic life cycle with an acute phase during initial infection and a subsequent latent phase. During latency, the virus remains “quiet” within host cells, expressing only a limited set of genes like latency-associated nuclear antigen (LANA).
The virus primarily infects B-lymphocytes and endothelial cells, which line blood vessels. While HHV-8 often causes no noticeable symptoms in healthy individuals, it can reactivate from its latent state. This reactivation can lead to cell proliferation and contribute to disease development, especially when the host’s immune response is compromised.
Diseases Linked to HSV-8
HHV-8 is the direct cause of Kaposi’s Sarcoma (KS), a cancer that forms lesions on the skin, in lymph nodes, or in internal organs. These lesions typically appear as reddish-purple patches, bumps, or nodules due to their rich blood vessel content. HHV-8 infection is a necessary factor for KS to develop, though other contributing factors like immune suppression are also needed.
Types of Kaposi’s Sarcoma
Classic KS: Affects older men of Eastern European, Mediterranean, or Middle Eastern descent.
Endemic KS: Common in sub-Saharan Africa, sometimes presenting aggressively in children.
Iatrogenic KS: Seen in organ transplant recipients due to immunosuppressive medications.
Epidemic (AIDS-related) KS: The most common form in the United States, occurring in individuals with HIV/AIDS.
The virus is also associated with Primary Effusion Lymphoma (PEL), a rare and aggressive B-cell lymphoma. PEL is characterized by cancerous fluid collections in body cavities like the pleural (lung), pericardial (heart), or peritoneal (abdominal) spaces, typically without forming solid tumor masses. Patients with PEL often experience symptoms such as shortness of breath or abdominal distension, along with systemic signs like fever, weight loss, and night sweats. This condition primarily affects immunocompromised individuals, particularly those with HIV infection, and often involves coinfection with Epstein-Barr virus (EBV).
Multicentric Castleman’s Disease (MCD) is another lymphoproliferative disorder linked to HHV-8. This condition involves the enlargement of multiple lymph nodes throughout the body, along with systemic inflammation. Symptoms can include persistent fever, fatigue, unintentional weight loss, muscle aches, and an enlarged spleen or liver. HHV-8-associated MCD is most frequently diagnosed in patients with weakened immune systems, such as those with HIV.
How HSV-8 Spreads and Who is at Risk
Human Herpesvirus 8 transmission occurs through several routes, with saliva being a common source of the infectious virus. Non-sexual close contact, such as within families in regions where the virus is common, contributes to its spread, particularly in childhood. The virus can be shed in saliva even when an infected individual shows no symptoms.
Sexual contact, especially oral-genital and anal sex, is another mode of transmission, with HHV-8 DNA detected in genital secretions and semen. While less common, transmission through organ transplantation and blood transfusions has also been reported. The risk of acquiring HHV-8 and developing associated diseases is higher in immunocompromised individuals, including those with HIV/AIDS and organ transplant recipients. High rates of infection, sometimes exceeding 80%, are observed in sub-Saharan Africa and intermediate levels in Mediterranean populations.
Detection and Treatment Approaches
Detecting HHV-8 infection commonly involves serologic assays, which look for antibodies against the virus in blood samples. These tests, such as immunofluorescence, ELISA, and Western blot, indicate past or present exposure to the virus. For direct detection, nucleic acid-based tests like polymerase chain reaction (PCR) are used to identify viral DNA in tissues, blood, or bodily fluids, particularly for diagnosing associated diseases. While HHV-8 DNA can be found in saliva and blood, its presence can vary, and routine testing for asymptomatic individuals is not typically recommended.
There is currently no cure for HHV-8 infection itself, as the virus remains latent in the body for life once acquired. Treatment strategies focus on managing the diseases caused by HHV-8, especially in immunocompromised individuals. For Kaposi’s Sarcoma, treatment often involves highly active antiretroviral therapy (ART) in HIV-infected patients, which can reduce KS incidence and improve outcomes by suppressing HIV replication. Localized KS lesions may be treated with surgery or radiation therapy, while more widespread disease might require systemic chemotherapy, sometimes combined with ART.
For Primary Effusion Lymphoma and Multicentric Castleman’s Disease, treatment typically involves chemotherapy. Antiviral drugs like ganciclovir or valganciclovir may also be considered for MCD. Rituximab, a medication that targets B-lymphocytes, is also used for HHV-8-associated MCD. Prevention strategies include practicing safe sexual behaviors to reduce transmission risk and, for immunocompromised individuals, managing underlying conditions to maintain a stronger immune system.