Molecular biology of human herpesviruses 6A and 6B.
Human herpesvirus 6 variant A (HHV-6A) and human herpesvirus 6 variant B (HHV-6B) are closely related herpesviruses. No disease has been specifically associated with HHV-6A, whereas HHV-6B is the major etiologic agent of exanthem subitum. Both viruses may be opportunistic pathogens in the immunocompromised patient. HHV-6 genomes have low G+C contents for herpesviruses (43%); they consist of a 141-kb unique segment that is flanked by single copies of a directly repeated sequence that can vary from 10 to 13 kb. HHV-6A and HHV-6B encode homologs of many conserved herpesvirus proteins and are classified as beta-herpesviruses based on their close genetic relationship with human cytomegalovirus. HHV-6A and HHV-6B are even more closely related to the recently discovered human herpesvirus 7. HHV-6 encodes homologs of the seven genes that are essential for origin-dependent herpes simplex virus type 1 DNA replication, including the origin-binding protein, which has no clear homolog in human cytomegalovirus. The HHV-6B origin-binding protein binds to sequences with similarities to alpha-herpesvirus replication origins that lie within a genomic segment that can serve as a replication origin in transient replication assays. Both HHV-6 variants encode homologs of the adeno-associated virus type 2 Rep protein; the role of this protein during infection is unknown. HHV-6 induces synthesis of a broad range of host cell proteins, including interferon alpha, CD4, interleukin-1 beta, and tumor necrosis factor alpha, and also induces expression of the human immunodeficiency virus type 1 LTR promoter. Little is known about the process by which HHV-6 regulates gene expression.
Inoue
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Centers for Disease Control and Prevention, Atlanta, Georgia 30333.
Dambaugh
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Pellett
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D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D001483:Base Sequence; D004265:DNA Helicases; D004261:DNA Replication; D004279:DNA, Viral / Q000096:biosynthesis / Q000378:metabolism; D004268:DNA-Binding Proteins; D000229:Dependovirus / Q000235:genetics; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D016679:Genome, Viral; D015654:Herpesvirus 6, Human / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D008969:Molecular Sequence Data; D012091:Repetitive Sequences, Nucleic Acid; D015534:Trans-Activators; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D015678:Viral Structural Proteins / Q000235:genetics; D014779:Virus Replication
D001426:Bacterial Proteins; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D015534:Trans-Activators; D015678:Viral Structural Proteins; C045264:replication initiator protein; D004265:DNA Helicases