Analysis of the ORFK1 hypervariable regions reveal distinct HHV-8 clustering in Kaposi's sarcoma and non-Kaposi's cases

J Exp Clin Cancer Res. 2015 Jan 16;34(1):1. doi: 10.1186/s13046-014-0119-0.

Abstract

Background: Classical Kaposi's Sarcoma (cKS) is a rare vascular tumor, which develops in subjects infected with Human Herpesvirus-8 (HHV-8). Beside the host predisposing factors, viral genetic variants might possibly be related to disease development. The aim of this study was to identify HHV-8 variants in patients with cKS or in HHV-8 infected subjects either asymptomatic or with cKS-unrelated cutaneous lymphoproliferative disorders.

Methods: The VR1 and VR2 regions of the ORF K1 sequence were analyzed in samples (peripheral blood and/or lesional tissue) collected between 2000 and 2010 from 27 subjects with HHV-8 infection, established by the presence of anti-HHV-8 antibodies. On the basis of viral genotyping, a phylogenetic analysis and a time-scaled evaluation were performed.

Results: Two main clades of HHV-8, corresponding to A and C subtypes, were identified. Moreover, for each subtype, two main clusters were found distinctively associated to cKS or non-cKS subjects. Selective pressure analysis showed twelve sites of the K1 coding gene (VR1 and VR2 regions) under positive selective pressure and one site under negative pressure.

Conclusion: Thus, present data suggest that HHV-8 genetic variants may influence the susceptibility to cKS in individuals with HHV-8 infection.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cluster Analysis
  • Female
  • Genetic Variation*
  • Herpesviridae Infections / virology*
  • Herpesvirus 8, Human / classification*
  • Herpesvirus 8, Human / genetics*
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Phylogeny
  • Sarcoma, Kaposi / genetics*
  • Viral Envelope Proteins / genetics*

Substances

  • Membrane Proteins
  • ORF-K1 protein, Human herpesvirus 8
  • Viral Envelope Proteins