Human herpesvirus 8--the first human Rhadinovirus

Area of Science:

• Virology
• Oncology
• Genomics

Background:

• Kaposi's sarcoma (KS)-associated herpesvirus (HHV-8) is a rhadinovirus found in KS, Castleman's disease, and body cavity-based B-cell lymphoma.
• Other rhadinoviruses cause lymphomas and hematopoietic cancers in various animal species.
• Rhadinovirus genomes typically contain sequences derived from host DNA.

Purpose of the Study:

• To clone and sequence the complete genome of human herpesvirus 8 (HHV-8).
• To identify genes within the HHV-8 genome with homology to known viral oncoproteins and cellular genes.
• To investigate the variability of specific HHV-8 genes.

Main Methods:

• Cloning and sequencing of the near-complete HHV-8 genome from a Kaposi's sarcoma biopsy.
• Bioinformatic analysis to identify open reading frames (ORFs) and compare them to known herpesvirus and cellular genes.
• Sequence analysis to assess the variability of the HHV-8 K1 reading frame.

Main Results:

• The HHV-8 genome was sequenced, revealing collinear organization and homology with herpesvirus saimiri.
• Genes homologous to cellular interleukin 6, macrophage inflammatory proteins (MIP1 alpha and MIP1 beta), an interferon-responsive factor, and two apoptosis inhibitors were identified.
• The HHV-8 K1 reading frame, a positional analogue of Stp/Tip oncoproteins, showed significant inter-strain variability.
• Homologues of known viral oncoproteins (Stp, Tip) were not identified in the HHV-8 genome.

Conclusions:

• The HHV-8 genome contains numerous cellular gene homologues, several of which code for functional proteins.
• The identified cellular homologues may play a role in the pathogenesis of HHV-8-associated diseases.
• The variability of the K1 gene suggests potential immune evasion mechanisms or adaptation strategies of HHV-8.