Herpèsvirus humain 8. Aspects virologiques, cliniques et épidémiologiques

Abstract

HHV-8 belongs to the herpesviridae family, to the gammaherpesvirinae sub-family and to the rhadinovirus genus. While several viral homologues exist in different types of non human primates, HHV-8 is the only rhadinovirus known in human. The HHV-8 genome comprises a unique long region of 140 kb, containing nearly 90 genes, with, at both extremities, terminal repeated regions that comprise identical repeated sequences in variable number. Among these genes, some encode proteins necessary for the viral replication and the assembly of new particles (structural proteins, DNA polymerase, glycoproteins), others in contrast, encode homologues of cellular protein involved in the regulation of the cell cycle, apoptotic cell death mechanisms and cellular proliferation. HHV-8 has indeed several genes which have been hijacked from the host during a long parallel evolution. These viral genes, divergent homologues of the original cellular genes, play a crucial role in the tumorigenesis mediated by HHV-8 but also in mechanisms leading to escape the anti viral immune response. HHV-8 is considered as the etiological agent of the four clinico-epidemiologic forms of Kaposi's sarcoma (classic, endemic, post-transplant and epidemic/HIV associated). This human oncogenic herpesvirus is also associated with primary effusion lymphoma and some cases of multicentric Castleman disease as well as other rare lymphomas. HHV-8 is not a ubiquitous virus. It is principally endemic in areas of high endemicity for classic or endemic Kaposi's sarcoma including the Mediterranean zone, and mostly East and Central Africa. In the latter areas, HHV-8 seroprevalence can reach 80% among the adult population. While in the HHV-8 highly endemic male homosexual population (mainly in the USA and Europe), this herpesvirus is transmitted during repeated sexual contacts, HHV- 8 transmission occurs mainly from mother to child and between siblings in the general population of endemic areas (Africa). Saliva seems to play a major role in the viral transmission, being a possible reservoir for HHV-8. Molecular epidemiological studies of the K1 gene (one of the most variable genomic region) have revealed the presence of different molecular subtypes which appear, at least some of them, mostly linked to the geographical origin of the samples rather than to the associated disease.