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Comparative Study
. 1999 Oct;73(10):8053-63.
doi: 10.1128/JVI.73.10.8053-8063.1999.

Comparison of the complete DNA sequences of human herpesvirus 6 variants A and B

Y Isegawa  1 , T Mukai, K Nakano, M Kagawa, J Chen, Y Mori, T Sunagawa, K Kawanishi, J Sashihara, A Hata, P Zou, H Kosuge, K Yamanishi
Affiliations
Comparative Study

Comparison of the complete DNA sequences of human herpesvirus 6 variants A and B

Y Isegawa et al. J Virol. 1999 Oct.

Abstract

Human herpesvirus 6 (HHV-6), which belongs to the betaherpesvirus subfamily and infects mainly T cells in vitro, causes acute and latent infections. Two variants of HHV-6 have been distinguished on the basis of differences in several properties. We have determined the complete DNA sequence of HHV-6 variant B (HHV-6B) strain HST, the causative agent of exanthem subitum, and compared the sequence with that of variant A strain U1102. A total of 115 potential open reading frames (ORFs) were identified within the 161,573-bp contiguous sequence of the entire HHV-6 genome, including some genes with remarkable differences in amino acid identity. All genes with <70% identity between the two variants were found to contain deleted regions when ORFs that could not be expressed were excluded from the comparison. Except in the case of U47, these differences were found in immediate-early/regulatory genes, DR2, DR7, U86/90, U89/90, and U95, which may represent characteristic differences of variants A and B. Also, we have successfully typed 14 different strains belonging to variant A or B by PCR using variant-specific primers; the results suggest that the remarkable differences observed were conserved evolutionarily as variant-specific divergence.

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Figures

FIG. 1
FIG. 1
Restriction fragments used for the sequencing of HHV-6 strain HST. The HHV-6 genome is represented diagrammatically, together with the positions of BamHI, HindIII, KpnI, and PstI sites. Various plasmid-cloned restriction fragments are prefixed with Ba, H, Kp, or pSTY (indicating their terminal restriction sites). Sequenced restriction fragments are indicated by shading.
FIG. 2
FIG. 2
Predicted ORF organization of HHV-6 strain HST. Repeat regions (DRL, DRR, R1, R2, and R3) are boxed; telomeric repeat regions (T1 and T2) are denoted by striped bars; UR is indicated by a solid line. Protein coding regions are indicated as open arrows and are numbered DR1, DR2, DR3, DR6, DR7, DR8, DRHN1, and DRHN2 within the direct repeats and HN1, HN2, HN3, and U1 to U100 (excluding U78, U88, U92, U93, and U96) within the UR. The Ori is indicated by an asterisk. These regions are further described in Table 1 and in the text. The US22 gene family is shaded. Abbreviations not given in text: GCR, G-protein-coupled receptor; Ig, Ig immunoglobulin superfamily; RR, large subunit of ribonucleotide reductase; mCP, minor capsid protein; CA, capsid assembly protein; Teg, tegument protein; Pol, DNA polymerase; tp, transport protein; mDBP, major single-stranded DNA binding protein; TA, conserved herpesvirus transactivator; dUT, dUTPase; Pts, protease/assembly protein; pp65/71, phosphoprotein 65/71K; MCP, major capsid protein; PT, phosphotransferase; Exo, exonuclease; OBP, origin binding protein; Hel, helicase; UDG, uracil-DNA glycosylase; Che, chemokine; AAV rep1, adeno-associated virus replication protein homolog.
FIG. 3
FIG. 3
PCR typing of HHV-6. (A, C, E, G, and I) Schematic primary structures of ORFs U95, U86, U47, U11, and DR2 of strains HST and U1102. Positions and directions of the PCR primers are indicated by arrowheads at vertical lines. (B, D, F, H, and J) PCR amplification of DNAs from isolates 1 to 15 (K) of HHV-6 and HHV-7. Templates were purified from peripheral blood mononuclear cells infected with several laboratory strains and clinical isolates and were amplified with PCR primers (L). The products were fractionated by electrophoresis on 6% polyacrylamide gels and stained with ethidium bromide. The PCR products are indicated by arrowheads in panels B, D, F, H, and J. (K) Viruses used in the experiment. CFS, chronic fatigue syndrome.
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