Kaposi’s sarcoma-associated herpesvirus (KSHV) is the ninth human herpesvirus discovered. This gammaherpesvirus is known for its association with various cancers. KSHV is the causative agent of Kaposi’s Sarcoma (KS), a vascular tumor, and several related lymphoproliferative disorders. Like all herpesviruses, KSHV establishes a lifelong infection in the host, often remaining dormant without causing disease. The virus is particularly concerning because its associated malignancies are most common and aggressive in individuals with compromised immune systems.
The Structure and Classification of Human Herpesvirus 8
KSHV is a large, enveloped virus that contains a double-stranded DNA genome of approximately 170 kilobases. It belongs to the Gammaherpesvirinae subfamily, which also includes the Epstein-Barr virus (EBV). The viral structure includes an outer lipid envelope, a protein layer called the tegument, and an inner icosahedral capsid protecting the DNA.
KSHV establishes latency, a long-term dormant state, primarily targeting B cells and endothelial cells for persistent infection. During latency, the viral genome exists as a circularized episome within the cell nucleus, tethered to host chromosomes by the Latency-Associated Nuclear Antigen (LANA) protein. Only a limited number of viral genes are expressed in this quiescent state, which maintain the viral genome and prevent cell death. Reactivation (the shift to the lytic cycle where new virus particles are produced) is often triggered by a weakening of the host’s immune surveillance.
Cancers and Conditions Associated with the Virus
KSHV is the definitive cause of Kaposi’s Sarcoma (KS), a cancer originating from the cells lining the lymph and blood vessels. The tumors appear as reddish-purple lesions most often on the skin, but they can also affect the lymph nodes and internal organs. KS is broadly categorized into four main epidemiological forms that share the same viral cause.
Forms of Kaposi’s Sarcoma
- The “classic” form typically affects older men of Mediterranean, Middle Eastern, or Eastern European descent and follows a slow, less aggressive course.
- The “endemic” form is found across sub-Saharan Africa and can be aggressive, especially in children, often involving the lymph nodes rather than just the skin.
- The “epidemic” or AIDS-associated form is the most common subtype in the United States and Europe, associated with advanced HIV infection.
- An “iatrogenic” form occurs in organ transplant recipients who are taking immunosuppressive medications.
Beyond Kaposi’s Sarcoma, KSHV is linked to two rare but aggressive B-cell lymphoproliferative disorders. Primary Effusion Lymphoma (PEL) is a lymphoma that grows in body cavities, such as the pleural, pericardial, or peritoneal spaces, without forming a solid tumor mass. Multicentric Castleman Disease (MCD) is a disorder characterized by the uncontrolled growth of lymph node cells, often presenting with systemic inflammatory symptoms like fever and fatigue. The manifestation of all KSHV-associated diseases is strongly influenced by the host’s immune status.
Transmission Routes and Populations at Highest Risk
KSHV transmission occurs through several routes, demonstrating that it is not solely a sexually transmitted infection. One of the most common methods of spread, especially in endemic regions, is through saliva, often via deep kissing or other forms of close oral contact. In young children in areas with high prevalence, non-sexual transmission through salivary exchange is considered the main route of acquisition.
Sexual contact is a recognized transmission route, particularly among men who have sex with men (MSM) in non-endemic areas like North America and Western Europe. The virus can also be transmitted through the transplantation of KSHV-infected organs or, less commonly, through blood transfusions. Vertical transmission from mother to child is possible, though it is considered rare.
The prevalence of KSHV infection varies dramatically around the world. Seroprevalence rates are relatively low in the general population of North America and Northern Europe, typically under 10%. However, rates are moderately higher in Mediterranean countries (20–30%) and exceptionally high in parts of sub-Saharan Africa, where they can exceed 50% in adults. Within low-prevalence countries, the highest-risk group is HIV-positive men who have sex with men, where KSHV prevalence can reach 25–35%.
Testing and Treatment Strategies
Diagnosis of KSHV infection begins with serological testing, which detects antibodies against the virus in a blood sample and reveals whether a person has ever been infected. For diagnosing active disease, clinicians rely on Polymerase Chain Reaction (PCR) to detect viral DNA in the blood or affected tissue, such as a biopsy of a lesion. Histological examination of tissue is also performed, and the presence of the KSHV protein LANA-1 can be confirmed through immunohistochemistry.
Currently, there is no vaccine to prevent KSHV infection, nor is there a cure once a person is infected. Treatment focuses on managing the resulting conditions like Kaposi’s Sarcoma, PEL, and MCD. For HIV-positive individuals, the cornerstone of management is Antiretroviral Therapy (ART), which restores the immune system and often leads to the regression of KS lesions. For active, more extensive lesions, direct treatment may involve chemotherapy, such as liposomal doxorubicin, or radiation therapy. Specific therapies like rituximab, an antibody targeting B-cells, are used to manage KSHV-associated MCD.