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or nodular lesions located in the lower extremity. In his clinical report, this sarcoma
was first observed on the feet of five men aged 40–68 years old; later evidence
showed that similar lesions were present in the trachea, esophagus, stomach, liver,
and bowel. He declared that this disease was incurable and patients will eventually
die within 5 years [ 1 ]. KS was considered rare for a long time since its description.
Until the 1980s, the annual incidence of KS was reported to be as low as 0.021–
0.061 per 100,000 in the United States, and it often occurred in elderly men [ 1 ].
Case reports indicated that the high-incidence areas were equatorial tropical Africa
or sub-Saharan Africa, Eastern Central Europe [ 2 ], Xinjiang of China [ 3 , 4 ], etc.
In 1981, Alvin Friedman-Kien firstly reported KS syndrome in 41 young homo-sexual men aged between 26 and 51 [ 2 ]. The discovery of acquired immunodefi-
ciency syndrome (AIDS) resulted in an increase in the number of AIDS-associated
KS cases. The outbreak of the AIDS epidemic in 1980s shifted attention to this
neoplastic complication of AIDS and its association with human pathogens. Much
effort has been made to identify the pathogens involved in KS. In 1972, typical
herpes-type virus particles were found in five of eight selected tissue culture lines
derived from different cases of KS [ 5 ], although one of these viruses was deter-
mined to be cytomegalovirus (CMV). Another study confirmed the presence of
“intranuclear herpes-type viral inclusions” in KS specimens [ 6 ]. The association
between AIDS and KS and the discovery of human immunodeficiency virus (HIV)
led to the assumption that HIV may be the causal agent of KS. However, this
hypothesis cannot explain the distinct distribution of KS among HIV patients with
different transmission pathways. For example, the incidence of KS is lower in
patients infected with HIV through blood products than in homosexual and bisexual
AIDS patients [ 7 ]. In addition, KS was initially reported in HIV-negative patients.
This phenomenon indicated that other environmental factors or infectious agents
may be responsible for the emergence of KS.
The breakthrough occurred in 1994 when Yuan Chang and Patrick Moore et al.discovered new sequences in KS lesions that were absent in control tissue using the
representational difference analysis (RDA) technique [ 8 ]. These new sequences
were similar but not the same as those of the Gammaherpesvirinae, such as
Herpesvirus saimiri and Epstein-Barr virus. It was later determined that they
belonged to a new human herpesvirus termed Kaposi’s sarcoma-associated herpes-
virus (KSHV). Further research demonstrated that KSHV is the etiological agent of
Kaposi’s sarcoma.
Herpesviridae is a large family of DNA viruses that cause diseases in variousanimals and humans. The formal name of KSHV is Human herpesvirus 8 (HHV-8)
according to the International Committee on Taxonomy of Viruses (ICTV). It
belongs to the Gammaherpesvirinae subfamily, which is characterized by lympho-
cytic tropism. The Gammaherpesvirinae subfamily can be further divided into five
genera according to the 2015 ICTV report of virus taxonomy, such as the
Lymphocryptoviridae, containing the human Epstein-Barr virus (EBV), and
Rhadinoviridae, containing human KSHV.
S. Li et al.