The complete HHV-8 genome sequence shows that it has sequence similarities to other gammaherpesviruses including, herpesvirus saimiri (HVS), murine gammaherpesvirus 68 (MHV68) and Epstein-Barr Virus (EBV). The ~165 kb genome contains over 80 open reading frames arranged in a long unique region flanked by multiple 801bp terminal repeat units of high G+C content. The long unique region contains blocks of conserved genes found in most herpesviruses, interspersed with blocks of non-homologous genes that are specific for HHV-8 and related viruses. HHV-8 proteins with recognizable homology to cellular proteins include:
There is a strong correlation (>95%) with KS in HIV+ and HIV- patients. The virus can be isolated from PBMC as well as KS tumour cells; appears to have a less ubiquitous world distribution than other HHVs???
Recent PCR studies have suggested that HHV-8 may be sexually-transmitted through semen, and that infection, in low titer and in a latent form, may be more prevalent in healthy subjects than initially thought and may be reactivated to replicate upon immunosuppression or other stimuli.
Recent evidence suggests that one of the genes of HHV-8, vGPCR (viral G-protein coupled receptor) acts as a vascular switch, turning on synthesis of a powerful angoigenic agent, vascular endothelial growth factor (VEGF), which is responsible for the development of KS. However, HHV-8 also contains a considerable number of other 'pirated' cellular genes in an 'oncogenic cluster' within the virus genome which may also be involved in the development of malignancy (see Boshoff, C. Nature 391: 24-25, 1998), e.g. the K1 gene (Nature Med. 4:435 1998).
In addition to KS, this virus may also cause other tumours such as B-cell lymphomas (±EBV as 'helper'). HHV-8 resembles EBV in that:
Epidemiological evidence now points to "... concurrent epidemics of HIV-1 and HHV-8 present among US homosexual men during the early 1980s" and that "the incidence of HHV-8 subsequently slowed dramatically in parallel with the incidence of HIV-1."