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transmission route for KSHV [ 62 ]. Studies in the AIDS-KS population showed that
KSHV is consistently detected in patients’ saliva, which is in a line with the study
in endemic KS [ 63 ]. However, further mechanistic studies are needed to explain the
epidemiological observations.
The susceptibility factors involved in KSHV infection and those involved in thedevelopment of KSHV-related diseases are two different but tightly related issues.
It is difficult to evaluate the susceptibility factors of KSHV infection using serop-
revalence data without specific surveys of the behavioral and biological background.
However, the existence of prevalence regions for endemic and classic KS suggests
that the host genetic and behavioral factors and environmental factors (certain vol-
canic soils, arthropod bites, and living in rural areas) may be involved in KSHV
infection [ 64 ]. For example, Uyghur and Kazakh ethnic groups, which live in the
Xinjiang province of China, have significantly higher rates of KSHV infection than
the Han population [ 65 ]. Although KSHV infection is necessary for the develop-
ment of KS, it is not sufficient for its pathogenesis. Susceptibility factors have been
identified for the oncogenic outcome of KSHV infection. Cases of AIDS-KS and
iatrogenic KS indicate that the immune status of the host is critical for the pathogen-
esis of KSHV infection [ 38 ]. However, a more direct role of HIV infection alone in
the development of the disease cannot be excluded [ 65 ]. Genetic polymorphisms of
inflammatory and immune-response genes have been associated with the classic KS
risk [ 38 ]. The susceptibility factors for the development of KSHV-related diseases
should be studied in the same background as that of KSHV infection.
7.2.3 KSHV-Related Diseases
7.2.3.1 Kaposi’s Sarcoma
KS can be classified into four subtypes according to geographical distribution and
clinical origins, namely, classic KS, endemic KS, iatrogenic KS, and AIDS-
related KS [ 42 ]. Dr. Moritz Kaposi first described the rare, frequently indolent
tumor of the skin in older men of Mediterranean and Eastern European origins
currently known as classic KS. Endemic KS, which is more aggressive than clas-
sic KS, was first described in the sub-Saharan region in the 1960s. Iatrogenic KS
was identified among immunosuppressive patients, such as those undergoing
transplantation surgery [ 66 ]. AIDS-related KS, the most common subtype,
robustly appeared along with the HIV pandemic. These subtypes are histologi-
cally indistinguishable regarding their clinical detection. KS lesions are charac-
terized by poorly formed and dilated vascular spaces, where the spindle-shaped
cell proliferates. These spindle cells are thought to be the KS tumor cells. The
infiltration of inflammatory mononuclear cells including lymphocytes, plasma cells,
and some macrophages is consistently observed in KS lesions [ 67 ]. The symptoms
of KS vary, ranging from indolence to aggressive tumors leading to significant
morbidity and mortality. Cutaneous lesions are mostly found in the lower
7 KSHV Epidemiology and Molecular Biology