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The history of the identification of human herpesvirus 8 (HHV-8; also
known as Kaposi sarcoma herpesvirus [KSHV] or
Kaposi sarcoma [KS] virus) was unique among the Herpesviridae insofar
as the virus was initially “discovered” purely
on a molecular biologic basis using a powerful detection technique.1 Working
with tissue from HIV- infected individuals with KS, Chang and colleagues
used a technique referred to as “representational difference
analysis” to identify disease-specific DNA sequences in
KS tissue. On DNA sequence analysis, the deduced amino acid sequences
were found to have strong homology to proteins from the gamma herpesvirus subfamily,
the subfamily of the Herpesviridae that includes
Epstein-Barr virus (EBV). This observation was striking in view
of the known ability of EBV to persist in lymphocytes, immortalize
cells, and produce human malignancies (Burkitt lymphoma and nasopharyngeal
carcinoma). Hence, the novel gamma herpesvirus, HHV-8, appeared
to be a new herpesvirus associated with human malignancy, Kaposi
sarcoma. Eventually HHV-8 was cultivated in tissue culture, proving
that these DNA sequences corresponded to a morphologically identifiable
viral particle.2
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The epidemiology of primary human herpesvirus 8 (HHV-8) infection
appears to vary considerably worldwide. The routes of acquisition
of infection and mechanisms responsible for person-to-person transmission
remain uncertain. After the virus was initially discovered, the
unique role it seemed to play in inducing malignant disease in HIV-infected
patients suggested that the primary route of transmission of HHV-8
was through sexual contact, particularly among gay men. However,
more recent evidence suggests that other routes of infection exist,
including transmission by saliva.4 A cross-sectional
study of the seroprevalence of HHV-8 in children and adolescents
in the United States indicated a prevalence of approximately 1%.5 There
appears to be considerable regional variation in prevalence in the
United States. In a population of children in south Texas, the seroprevalence
was 26%, strongly suggesting that nonsexual modes of transmission
predominate.6 In sub-Saharan Africa, prevalence in
children is even higher, approaching 60% in some studies (reviewed
in 7). There are reports of maternal-to-child transmission that
suggest the possible of vertical infection (reviewed in 8), but the
mechanisms of transmission and clinical manifestations in newborns
are unclear. HHV-8 can also be transmitted by blood transfusion.9 As
serologic and nucleic acid-based diagnostics tests become more widely
available, a better assessment of the worldwide seroepidemiology
of HHV-8 infection will become feasible.
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Structurally, human herpesvirus 8 (HHV-8) consists of a prototypical
enveloped particle, morphologically similar to other herpesviruses.
The virus presumably establishes latent infection following primary
infection, although the site(s) of latency are unknown. Evolutionarily,
HHV-8 appears to have undergone considerable recombination with
host genes, and the viral genome contains a variety of transduced
cellular oncogenes and chemokine homologs that are probably important
in the pathogenesis of KS.3 It is estimated that
10% of the genes encoded by HHV-8 promote KS development
due to mitogenic, antiapoptotic, chemoattractive, angiogenic, or
transforming activities.