Kaposi's sarcoma-associated herpesvirus
From Freepedia
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Kaposi's sarcoma-associated herpesvirus (KSHV) is the eighth human herpesvirus; its formal name according to the International Committee on Taxonomy of Viruses is HHV-8. This virus causes Kaposi's sarcoma, a cancer commonly occurring in AIDS patients, as well as primary effusion lymphoma and some types of multicentric Castleman's disease.
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History
It was first found by Yuan Chang and Patrick Moore, a wife and husband team at Columbia University in 1994, by isolating DNA fragments of the virus from a Kaposi's sarcoma tumor in an AIDS patient. Until then scientists had been searching for the agent causing Kaposi's sarcoma for over 20 years. Numerous agents had been proposed to cause Kaposi's sarcoma, including most famously the HIV virus itself as proposed by Robert Gallo. The discovery of this herpesvirus sparked considerable controversy and scientific in-fighting until sufficient data had been collected to show that indeed KSHV was the causative agent of Kaposi's sarcoma.
The virus is now known to be a widespread infection of people living in sub-Saharan Africa; intermediate levels of infection occur in Mediterranean populations (including Israel, Saudi Arabia, Italy and Greece) and low levels of infection occur in most Northern European and North American populations.
Virology
KSHV is one of the most exciting subjects in virology since it is a new model virus that shows how viruses can cause tumors. KSHV is something of a molecular Rosetta stone, since it possesses many genes that are known to cause human cancers but at the same time it has a clear relationship to other, more obscure tumor viruses. For this reason, it is a missing link that allows us to interpret the molecular virology of tumor viruses in terms of modern cancer biology.
KSHV is a herpesvirus, and is a large double-stranded DNA virus with a protein covering that packages its nucleic acids, called the virion, which is then surrounded by an amorphous protein layer called the tegument, and finally enclosed in a lipid envelope derived in part from the cell membrane. KSHV has a genome which is approximately 165,000 nucleic acid bases in length. It is a rhadinovirus, and is remarkable since it has stolen numerous genes from host cells including genes that encode for interleuken-6, BCL-2, cyclin, a G protein-coupled receptor, interferon regulatory factor and many others. While no other human tumor virus possesses these same genes, many of these genes target the same cellular pathways targeted by other tumor viruses illustrating that at a basic level, all tumor viruses appear to attack the same cellular control pathways, so-called tumor suppressor pathways.
After infection, the virus enters into lymphocytes where it remains in a latent ("quiet") state. The virus exists as a naked circular piece of DNA called an episome and uses the cellular replication machinery to replicate itself. Various signals such as inflammation may provoke the virus to enter into "lytic replication". When this occurs, the viral episome starts replicating itself in linear molecules that are packaged into virus particles that are expelled from the cell, to infect new cells or to be transmitted to a new host. When the virus enters into lytic replication, thousands of virus particles can be made from a single cell, which results in cell death.
Epidemiology
KSHV is an uncommon infection in the United States and in northern Europe, where less than 2% of the general population is infected with the virus. Gay and bisexual men, however, are at high risk for infection with up to 60% of gay men being infected in some studies. Among gay men, increasing numbers of sex partners increases the risk for infection. Unlike HIV, it is not clear that the virus is transmitted through unprotected anal intercourse. Instead, it is likely that it is transmitted between sex partners by oral secretions (e.g. saliva). The exact reasons why gay men are at high risk for infection compared to heterosexuals remains obscure, although it has been suggested that men in general may be more susceptible to the virus and therefore more likely to transmit it to male sex partners.
In African countries, in contrast, infection is spread through non-sexual routes that remain poorly understood. Young children can be infected (although direct transmission from mothers to their children during pregnancy is uncommon), and rates of infection can continue to increase throughout adulthood. A form of Kaposi's sarcoma occurring in young African children due to this infection is almost uniformly and rapidly fatal. Infection with the KSHV, however, is usually without symptoms in most persons. In addition to gay men and African populations, this infection is of particular concern to persons receiving organ transplants. Not only is there a risk of transmitting the virus from the donated organ, but recipients are immunosuppressed to avoid organ rejection and are at high risk for developing the tumor if the are infected. In some studies up to 50% of transplant recipients who are infected with KSHV will develop Kaposi's sarcoma, which can be life-threatening and can cause loss of the donated organ.
Infection with this virus is thought to be life-long, but a healthy immune system will keep the virus in check. Kaposi's sarcoma occurs when someone who has been infected with KSHV becomes immunocompromised due to AIDS, old age or medical treatment. Since persons infected with KSHV will asymptomatically shed the virus, caution should be used by sex partners in having unprotected sex and activities where saliva might be shared such as deep-kissing. Blood tests to detect infection exist, but they are largely restricted to research universities, since biomedical companies have not found it economical to develop these tests.
Treatment
Kaposi's sarcoma is usually a localized tumor that can be treated either surgically or through local irradiation. Chemotherapy may be used, particularly for invasive disease. Antiviral drugs, such as ganciclovir, that target KSHV have been used to successfully prevent development of Kaposi's sarcoma, although once the tumor develops these drugs are of limited usefulness. For patients with AIDS-KS, the most effective therapy is highly active antiretroviral therapy to reduce HIV infection. AIDS patients receiving adequate anti-HIV treatment may have up to a 90% reduction in Kaposi's sarcoma occurrence.
