The history of the identification of human herpesvirus-8 (HHV-8; also known as Kaposi sarcoma herpesvirus [KSHV] or Kaposi sarcoma [KS] virus) is unique insofar as the virus was initially “discovered” purely with the use of molecular detection techniques and not traditional viral cell culture. On sequence analysis of tissues amplified from KS patients, 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 (eg, Burkitt lymphoma and nasopharyngeal carcinoma). Hence, the novel gamma-herpesvirus, HHV-8, appeared to be a new herpesvirus associated with human malignancy—KS.
PATHOGENESIS AND EPIDEMIOLOGY
Structurally, 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. It is estimated that 10% of the genes encoded by HHV-8 promote KS development due to mitogenic, antiapoptotic, chemoattractive, angiogenic, or transforming activities.
The epidemiology of primary HHV-8 infection appears to vary considerably worldwide. The routes of acquisition of infection and mechanisms responsible for person-to-person transmission remain uncertain, although a role for salivary transmission in infants has been described. A cross-sectional study of the seroprevalence of HHV-8 in children and adolescents in the United States indicated an overall prevalence of approximately 1%, although considerable regional variation was observed. In sub-Saharan Africa, prevalence in children is much higher, approaching 60% in some studies. In addition to person-to-person routes of infection, HHV-8 can also be transmitted by blood transfusion.
Most primary infections with HHV-8 are probably asymptomatic, although the clinical course of primary symptomatic HHV-8 infections in a case series in immunocompetent children, some of whom had fever and rash, has been described. In this case series, the rash was first noted to appear on the face and it gradually spread to the trunk, arms, and legs. It initially consisted of discrete red macules that blanched with pressure and eventually became papular. The median duration of the rash was 6 days; fever persisted for a median of 10 days, and some children had high fever (temperature 39°C). An upper respiratory tract infection occurred in most of these children, and a lower respiratory tract infection appeared in one-third, although major respiratory complications did not occur during the course of primary HHV-8 infection.
Prior HHV-8 infection appears to be generally necessary, but not sufficient, for the development of KS, which is a multifocal vascular neoplasm involving skin, visceral organs, and lymph nodes. Lesions histopathologically contain ...