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Human herpesvirus 8 (Kaposi sarcoma)

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Human herpesvirus 8 (Kaposi sarcoma)

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A 46-year-old man comes to his primary care provider regarding mouth discomfort and bleeding for the past several weeks. He noticed bleeding after brushing his teeth. The patient's medical history is notable for HIV infection, and he says that he has been poorly compliant with his antiretroviral medication. Physical examination shows an intraoral dark-brown lesion with an overlying plaque which is easily scraped. Biopsy of the lesion shows significant lymphocyte infiltration and the presence of spindle cells. Which of the following is the most likely diagnosis?  



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Content Reviewers:

Viviana Popa, MD

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.