Human Herpesvirus 8 (HHV-8), also known as Kaposi’s sarcoma-associated herpesvirus (KSHV), is a common human herpesvirus. This double-stranded DNA virus is capable of establishing a lifelong infection in the body, where it can remain dormant for extended periods. Like other herpesviruses, HHV-8 can switch between a latent phase, where it silently exists within cells, and a lytic phase, where it actively replicates. Most infected cells typically exist in this latent phase.
Understanding Herpes Virus 8
HHV-8 is classified as a gammaherpesvirus, a subgroup of the Herpesviridae family that primarily infects lymphocytes. This virus can infect various cell types, including monocytes, B lymphocytes, and endothelial cells, which are cells lining blood vessels.
The primary modes of HHV-8 transmission vary geographically but include saliva, sexual contact, organ transplantation, and blood transfusions. Salivary exchange, particularly through deep kissing, is considered a significant route, especially in regions with high prevalence. Sexual transmission is also documented, with higher rates observed in men who have sex with men. While less common, transmission through organ transplantation and blood transfusions has been reported.
Many individuals infected with HHV-8 remain asymptomatic throughout their lives, with a healthy immune system often keeping the virus in check. Seroprevalence, or the presence of antibodies indicating past infection, can range from 1% to 5% in the United States and Northern Europe, but can be as high as 30% to 80% in parts of Sub-Saharan Africa.
Diseases Associated with Herpes Virus 8
HHV-8 is the underlying cause of several serious conditions, primarily affecting individuals with weakened immune systems. These conditions typically manifest when the immune system is compromised, such as in patients with HIV/AIDS, organ transplant recipients, or, in rare instances, the elderly. Infection with HHV-8 is a necessary factor for these diseases to develop, but it is not sufficient on its own.
Kaposi’s Sarcoma (KS)
Kaposi’s Sarcoma is an angioproliferative tumor, meaning it involves the abnormal growth of cells lining blood vessels. It often presents as dark purple, red, or brownish lesions on the skin, which can appear as macules, plaques, or nodules. These lesions can also affect lymph nodes and internal organs, including the gastrointestinal tract and lungs. While cutaneous lesions are the most noticeable, visceral involvement can be life-threatening. In HIV-infected individuals, KS was once a common malignancy, but its incidence has significantly decreased with the advent of effective antiretroviral therapy (ART).
Primary Effusion Lymphoma (PEL)
Primary Effusion Lymphoma is a rare and aggressive form of B-cell non-Hodgkin lymphoma that typically presents as fluid accumulation in body cavities like the pleural (around the lungs), pericardial (around the heart), or peritoneal (abdominal) cavities, without forming a solid tumor mass. PEL is almost universally associated with HHV-8, and in many cases, co-infection with Epstein-Barr virus (EBV) is also observed. This lymphoma carries a poor prognosis, particularly in immunocompromised individuals.
Multicentric Castleman’s Disease (MCD)
Multicentric Castleman’s Disease associated with HHV-8 (HHV-8+MCD) is a rare lymphoproliferative disorder characterized by the enlargement and overactivity of multiple lymph nodes throughout the body. This condition results from uncontrolled HHV-8 infection, which leads to an overproduction of immune cells and signaling proteins called cytokines, such as interleukin-6 (IL-6). Symptoms can be slow to develop or sudden and severe, often mimicking inflammatory illnesses with fever, night sweats, weight loss, and fatigue. HHV-8+MCD is most frequently diagnosed in individuals with HIV, and patients with this condition face an increased risk of developing other lymphomas and Kaposi’s Sarcoma.
Diagnosis and Management
Diagnosing HHV-8 infection and associated diseases involves various laboratory methods. Blood tests are commonly used to detect antibodies against HHV-8, indicating past exposure to the virus. These serological assays can target both lytic and latent antigens of the virus.
Polymerase Chain Reaction (PCR) is another diagnostic tool used to detect HHV-8 viral DNA in tissue samples, blood, saliva, or other body fluids. While PCR can detect viral DNA in almost all Kaposi’s Sarcoma lesions, viral DNA loads in peripheral blood cells may not always be high enough for detection in asymptomatic individuals. The definitive diagnosis of HHV-8-associated diseases like Kaposi’s Sarcoma, Primary Effusion Lymphoma, or Multicentric Castleman’s Disease often requires a tissue biopsy followed by histopathological examination and immunohistochemical staining to identify HHV-8-encoded latency-associated nuclear antigen (LANA-1) or viral DNA.
Management of HHV-8-associated diseases often involves a multi-pronged approach tailored to the specific condition and the patient’s immune status. For individuals with weakened immune systems, particularly those with HIV, strengthening the immune system through effective antiretroviral therapy (ART) is a primary treatment approach and can significantly reduce the risk and progression of HHV-8-associated malignancies, including Kaposi’s Sarcoma. Antiviral agents such as ganciclovir and foscarnet have shown activity against HHV-8 replication and may be used in certain situations to prevent or manage disease progression, although their routine use for prevention is not broadly recommended. Specific therapies for associated cancers may include chemotherapy, especially for disseminated or visceral Kaposi’s Sarcoma, and medications like rituximab for lymphoproliferative disorders that target HHV-8 infected B cells. Preventing transmission involves awareness of the primary routes, such as avoiding deep kissing with infected individuals and practicing safe sexual behaviors.