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The DNA sequence of human herpesvirus-6: structure, coding content, and genome evolution
U A Gompels1, J Nicholas, G Lawrence
1Department of Clinical Sciences, London School of Hygiene and Tropical Medicine, University of London, United Kingdom.
Virology
|May 10, 1995
Summary
The complete DNA sequence of human herpesvirus-6 was determined, revealing 102 genes and structural similarities to human cytomegalovirus. This provides insights into herpesvirus evolution and potential immune evasion strategies.
Area of Science:
- Virology
- Genomics
- Molecular Biology
Background:
- Human herpesvirus-6 (HHV-6) is a CD4+ T-lymphotropic virus implicated in diseases within immunodeficient individuals and potentially complicating AIDS.
- Understanding the HHV-6 genome is crucial for comprehending its pathogenesis and evolutionary relationships within the herpesvirus family.
Purpose of the Study:
- To determine the complete DNA sequence of the human herpesvirus-6 (HHV-6) strain U1102.
- To analyze the genome's structure, gene content, and evolutionary relationships with other herpesviruses.
- To identify potential HHV-6 genes involved in immune evasion and persistence.
Main Methods:
- Whole-genome sequencing of HHV-6 strain U1102.
- Bioinformatic analysis of the DNA sequence, including open reading frame identification and gene prediction.
- Comparative genomic analysis with other sequenced herpesviruses (human cytomegalovirus, herpesvirus saimiri, Epstein-Barr virus, equine herpesvirus-1, varicella-zoster virus, herpes simplex virus).
- Amino acid sequence comparison to infer protein functions.
Main Results:
- The complete HHV-6 genome sequence is 159,321 bp with 43% G+C content and 119 open reading frames, encoding 102 potential protein-coding genes.
- The genome structure features direct repeats (DRL and DRR) containing telomere-like repeats, with some genes duplicated or spanning these repeats.
- HHV-6 genes are colinearly arranged with human cytomegalovirus (a betaherpesvirus) but distinct from gammaherpesviruses and alphaherpesviruses.
- Predicted proteins show the highest homology (67%) to human cytomegalovirus, significantly more than to other herpesviruses (21%).
- Four distinct gene families, including homologs of chemokines, G-protein-coupled receptors, and immunoglobulin superfamily members, were identified, potentially involved in immune modulation.
Conclusions:
- The genomic sequence and gene organization of HHV-6 provide a framework for understanding its biology and evolution within the betaherpesvirus subfamily.
- The close relationship to human cytomegalovirus suggests shared ancestral origins and functional similarities.
- The presence of unique gene families offers potential targets for HHV-6 immune evasion and persistence mechanisms, warranting further investigation.