Human herpesvirus 8 (Kaposi sarcoma)

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A 45-year-old man comes to the clinic with skin lesions over his trunk, abdomen, and face. The patient also notes significant weight loss over the last six months. Past medical history is significant for gastroesophageal reflux disease, alcoholic cirrhosis, and esophageal varices. The patient was admitted two months ago for bleeding esophageal varices and underwent endoscopic variceal ligation. The patient is sexually active with men and women and uses condoms inconsistently. The patient uses intravenous drugs, including morphine, and consumes alcohol regularly. Temperature is 36.6°C (98.0°F), pulse is 99/min, respirations are 20/min, and blood pressure is 120/75 mmHg. Physical examination reveals anterior and posterior cervical lymphadenopathy. Oral examination reveals white mucosal plaques that cannot be scraped off easily. Skin lesions on the right arm are depicted below. This patient’s clinical presentation suggests which of the following underlying conditions?
 
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By Unknown author - National Cancer Institute, AV-8500-3620, Public Domain      

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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.

Summary

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.

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