96
The genetic diversity can only be found among different individuals, which means
the viral sequences are stable in a given individual [ 46 ]. KSHV-infected individuals
in Europe, the United States, the Middle East, and Asia are majorly A and C sub-
types, whereas viral isolates from sub-Saharan Africa belong to the B strain. The
type D strain is found primarily in Australia, South Asia, and the Pacific Islands
[ 38 ]. The A and C subgroups (and only rare B isolates) have two allelic variants,
termed P (for prototype) and M (for minority) in the K15 coding sequence. The P
and M K15 isolates share 33% amino acid identity [ 45 ]. Additional alleles (N and
Q) were reported in a recent study [ 48 ]. The diversity of the KSHV genome is also
related to its pathogenesis, as suggested by a few studies. Subtype A is the predomi-
nant KSHV subtype in HIV-positive patients in Brazil, whereas subtype C is found
mostly in the HIV-negative population [ 49 , 50 ]. KSHV subtype A is also more fre-
quent than subtype C in China [ 51 ]. Patients with rapid progression of KS are
infected by KSHV subtype A, whereas KSHV subtype C is related to slow progres-
sion [ 52 ]. Additional evidence is necessary to support the relationship between
genetic diversity and KSHV pathogenesis.
7.2.2 Transmission Routes and Susceptibility Factors
The most obvious transmission route of KSHV is sexual or blood-borne transmis-
sion, reflecting the high prevalence of KS in the AIDS population. Another signifi-
cant fact is that the seroprevalence of KSHV infection can range from 25% to 60%
in the homosexual population [ 53 ]. The seroprevalence rates are lower among
women than men, but heterosexual transmission occurs. Blood-borne transmission
(blood transfusion) of KSHV was documented in a prospective observational cohort
study [ 54 ]. However, a historical cohort study showed that there is no statistically
significant difference in KSHV seroconversion between the transfusion and non-
transfusion groups [ 38 ]. The incidence of KS is also high in organ transplant recipi-
ents because of immunosuppressive therapy, and this is known as iatrogenic KS
[ 55 ]. Iatrogenic KS may originate from the donor, although the evidence of this is
weak, and there are no formal guidelines for the clinical screening of organ trans-
plantation patients [ 38 ].
In addition to the studies of AIDS-KS and iatrogenic KS regarding the routes oftransmission, important epidemiological studies have been performed in the
endemic KS population in Africa [ 56 – 58 ]. Reports of KSHV-infected children in
endemic regions suggest that KSHV infection can occur at a very early age and the
transmission routes of KSHV are not limited to sexual or blood-borne transmission.
A strong familial association (a child is positive if the mother or a sibling is positive
for KSHV infection) in endemic regions has been reported [ 59 , 60 ]. Studies in rural
Uganda further support that KSHV infection in endemic regions is transmitted
mostly through nonsexual routes (contacts with family members in childhood and
continued into adulthood) [ 61 ]. Moreover, KSHV viral particles can be found in the
maternal saliva and breast milk in endemic areas, which suggests an ora1/salivary
S. Li et al.