Human herpesvirus 8 (Kaposi sarcoma)

Definitions & Key takeaways

Human herpesvirus 8 (HHV-8) also known as Kaposi's sarcoma-associated herpesvirus, is a double-stranded DNA virus known to cause a type of cancer called Kaposi sarcoma. Kaposi sarcoma is most commonly found in individuals with HIV/AIDS, and generally affects the skin, mucous membranes, lymph nodes, the GI tract, and lungs.

Watch video only
Human herpesvirus 8, or HHV-8, also called Kaposi’s sarcoma-associated herpesvirus, or KSHV, belongs to the family of human gamma herpesviruses.
HHV-8 is one of the seven known oncoviruses, meaning viruses that cause cancer in people. Specifically, HHV-8 causes Kaposi’s sarcoma, a type of cancer usually seen in individuals with AIDS.
Human herpesvirus 8 is a large double stranded linear DNA virus surrounded by an icosahedral capsid, which is a spherical protein shell made up of 20 equilateral triangular faces.
The capsid is covered by a protein layer called the tegument, and finally enclosed in an envelope, which is a lipid membrane that contains viral glycoproteins and is acquired from the nuclear membrane of host cells.
HHV-8 is transmitted through sexual contact and once in the body it uses the viral glycoproteins on its envelope to enter a wide variety of cells such as B cells, endothelial cells, macrophages and epithelial cells.
Now, the virus life cycle has two phases - a latent phase and a lytic phase. In the latent phase, the virus just hangs out in the cell without destroying it, and expresses the viral latency-associated nuclear antigen, or LANA-1.
This may sound harmless, but LANA-1 inhibits p53, a tumor suppressor protein that prevents cancer formation. So when LANA-1 inhibits p53, that prevents apoptosis and leads to uncontrolled cellular proliferation.
In the lytic phase, the virus starts to replicate, so its DNA gets transcribed and translated by cellular enzymes, in order to form viral proteins, which are packaged into new viruses.
When the virus enters into the lytic phase, thousands of virus particles can be made from a single cell which can destroy the cell and subsequently infect neighboring cells.
Now, the body’s immune system reacts to the infection by mounting a humoral response, where the B cells create antibodies to fight off the virus, and a cellular response, in which cytotoxic T cells work to kill the infected cells, limiting their ability to spread to other tissues.
So, in people with a healthy immune system, infection rarely occurs. However, people who are immunocompromised, such as people with AIDS, people who have undergone an organ transplant or people who take immunosuppressive medications, are at risk for developing the disease.
Specifically, HHV-8 causes a disease called Kaposi’s sarcoma which is classified into 4 types depending on the clinical circumstances in which it develops: classic, endemic, epidemic and immunosuppression therapy-related.
So, classic Kaposi’s sarcoma usually affects older males, it’s slow growing and it usually affects the legs. Endemic Kaposi’s sarcoma occurs in young adult males who live in Africa and can be more aggressive.
Epidemic Kaposi’s sarcoma is associated with AIDS and can affect many body parts such as skin, mouth, GI tract or lungs.
Finally, immunosuppression therapy-related Kaposi’s sarcoma affects the skin, and it usually develops following organ transplantation.
Now, regardless of type, Kaposi’s sarcoma is an endothelial cell neoplasm, so it causes vascular proliferation, resulting in dark or violaceous plaques.
These lesions are typically found on the skin, especially on lower limbs, back, face and genitalia, but they can also affect the mouth, GI tract and lungs.
Lesions in the mouth are usually found on the hard palate and gums and they can be easily damaged by chewing, so they can bleed or get infected.
Involvement of the GI tract can be asymptomatic or it can cause weight loss, nausea, vomiting, diarrhea, bleeding, malabsorption or intestinal obstruction.
When the lungs are involved, that can cause shortness of breath, chest pain, cough, and hemoptysis, which means coughing up blood.
Diagnosis of Kaposi’s sarcoma requires a biopsy of the lesions. Microscopic examination can show tumor cells with a characteristic abnormal elongated shape, called spindle cells.
And immunohistochemical staining of biopsy specimens can detect the presence of LANA-1 within the spindle cells and confirming the diagnosis.
Finally, viral DNA can be identified with PCR. Treatment is mainly aimed to stop the progression of Kaposi’s sarcoma, as the disease is not curable.
So when it occurs in individuals with immunodeficiency, treating the cause of the immune system dysfunction can slow or stop the progression of KS.
For example, in HIV infected individuals, treatment is done using highly active antiretroviral therapy, or HAART, which leads to HIV suppression that may shrink Kaposi’s sarcoma lesions.
In all types of KS, skin lesions can be treated with local measures such as radiation therapy or cryosurgery, and in cases of widespread disease with involvement of internal organs, chemotherapy can be used with anthracyclines such as doxorubicin or daunorubicin, thalidomide or paclitaxel.
All right, as a quick recap. Human herpesvirus 8 is a double-stranded DNA virus which causes a type of cancer that most commonly occurs in AIDS patients, called Kaposi’s sarcoma.
HHV-8 expresses a viral antigen called LANA-1 which prevents apoptosis and facilitates uncontrolled cellular proliferation.
Kaposi’s sarcoma affects most commonly the skin but it can also affect mouth, GI tract and lungs. Diagnosis is made with biopsy of lesions and microscopic examination which can detect spindle cells and also with immunohistochemical staining which detect the presence of LANA-1.
Treatment in HIV infected individuals is done with highly active antiretroviral therapy, or HAART, and treatment of widespread disease is done using chemotherapy.