Kaposi's sarcoma-associated herpesvirus (KSHV) is the ninth known human herpesvirus; its formal name according to the International Committee on Taxonomy of Viruses (ICTV) is Human gammaherpesvirus 8, or HHV-8 in short. Like other herpesviruses, its informal names are used interchangeably with its formal ICTV name. This virus causes Kaposi's sarcoma, a cancer commonly occurring in AIDS patients, as well as primary effusion lymphoma, HHV-8-associated multicentric Castleman's disease and KSHV inflammatory cytokine syndrome. It is one of seven currently known human cancer viruses, or oncoviruses. Even after many years since the discovery of KSHV/HHV8, there is no known cure for KSHV associated tumorigenesis.
History
In 1872, Moritz Kaposi described a blood vessel tumor (originally called "idiopathic multiple pigmented sarcoma of the skin") that has since been eponymously named Kaposi's sarcoma (KS). KS was at first thought to be an uncommon tumor of Jewish and Mediterranean populations until it was later determined to be extremely common throughout sub-Saharan African populations. This led to the first suggestions in the 1950s that this tumor might be caused by a virus. With the onset of the AIDS epidemic in the early 1980s, there was a sudden resurgence of KS affecting AIDS patients, with up to 50% of reported AIDS patients having this tumor—an extraordinary rate of cancer predisposition.
Careful analysis of epidemiologic data by Valerie Beral, Thomas Peterman and Harold Jaffe, led these investigators to propose that KS is caused by an unknown sexually transmitted virus that rarely causes tumors unless the host becomes immunosuppressed, as in AIDS.
As early as 1984, scientists reported seeing herpesvirus-like structures in KS tumors examined under electron microscopy. Scientists had been searching for the agent causing KS, and over 20 agents were proposed as the possible cause, including cytomegalovirus and HIV itself. The pathogen was ultimately identified in 1994 by Yuan Chang and Patrick S. Moore, a wife and husband team at Columbia University, through the isolation of DNA fragments from a herpesvirus found in a KS tumor in an AIDS patient. Chang and Moore used representational difference analysis, or RDA, to find KSHV by comparing KS tumor tissue from an AIDS patient to his own unaffected tissue. The idea behind this experiment was that if a virus causes KS, the genomic DNA in the two samples should be precisely identical except for DNA belonging to the virus. In their initial RDA experiment, they isolated two small DNA fragments that represented less than 1% of the actual viral genome. These fragments were similar (but still distinct from) the known herpevirus sequences, indicating the presence of a new virus. Starting from these fragments, this research team was then able to sequence the entire genome of the virus less than two years later.
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 Lebanon, Saudi Arabia, Italy, and Greece) and low levels of infection occur in most Northern European and North American populations. Gay and bisexual men are more susceptible to infection (through still unknown routes of sexual transmission) whereas the virus is transmitted through non-sexual routes in developing countries.