Human herpesvirus 6 is closely related to human cytomegalovirus

Abstract

The sequence has a mean composition of 41% G+C, and the observed frequency of CpG dinucleotides is close to that predicted from this mononucleotide composition. The sequence contains 17 complete open reading frames (ORFs) and part of another at the 5' end of the sequence. The predicted protein products of two of these ORFs have no recognizable homologs in the genomes of other sequenced human herpesviruses (i.e., Epstein-Barr virus [EBV], human cytomegalovirus [HCMV], herpes simplex virus [HSV], and varicelia-zoster virus [VZV]). However, the products of nine other ORFs are clearly homologous to a set of genes that is conserved in all other sequenced herpesviruses, including homologs of the alkaline exonuclease, the phosphotransferase, the spliced ORF, and the major capsid protein genes. Measurements of similarity between these homologous sequences showed that HHV-6 is clearly most closely related to HCMV. The degree of relatedness between HHV-6 and HCMV was commensurate with that observed in comparisons between HSV and VZV or EBV and herpesvirus saimiri and significantly greater than its relatedness to EBV, HSV, or VZV. In addition, the gene for the major capsid protein and its 5' neighbor are reoriented with respect to the spliced ORFs in the genomes of both HHV-6 and HCMV relative to the organization observed in EBV, HSV, and VZV. Three ORFs in HHV-6 have recognizable homologs only in the genome of HCMV. Despite differences in gross composition and size, we conclude that the genomes of HHV-6 and HCMV are closely related. sequence continues on the following pages.

Human herpesvirus‐6 infection: A prospective study evaluating HHV‐6 DNA levels in liver from children with acute liver failure

“…Human herpesvirus-6 (HHV-6) was first isolated from patients with lymphoproliferative disorders and acquired immunodeficiency syndrome (AIDS) [Salahuddin et al, 1986]. HHV-6 is a lymphotropic virus classified in the Betaherpesvirinae subfamily, along with human cytomegalovirus (HCMV) and HHV-7 [Lawrence et al, 1990;Berneman et al, 1992]. HHV-6 isolates are classified into two variants, termed A and B, on the basis of distinct genetic, antigenic and biological characteristics [Aubin et al, 1991;Ablashi et al, 1993].…”

Human herpesvirus 6 infection after living related liver transplantation

“…All human herpesviruses recognized previously, especially cytomegalovirus (CMV), have been implicated as important causes of morbidity and mortality in immunosuppressed organ transplant recipients. HHV-6 shares many characteristics with CMV [Efstathiou et al, 1988;Lawrence et al, 1990], including DNA sequence homology, some elements of genomic organization, antigenic cross-reactivity, and similar in vitro growth characteristics. Thus, HHV-6 might play an important role in the morbidity and mortality of organ transplant recipients.…”

Human herpesvirus-6 and human herpesvirus-7 infections in bone marrow transplant recipients

“…All human herpesviruses known to date are important pathogens in immunocompromised hosts, human cytomegalovirus (HCMV) being associated with the greatest morbidity and mortality. HHV-6 and HHV-7 are ␤-herpesviruses closely related to HCMV [Lawrence et al, 1990]. The lymphotrophic nature of HHV-6 and HHV-7; the in vitro observations that these viruses affect expression of interferon (IFN), interleukin (IL)-8, IL-1␤, and tumor necrosis factor-␣ (TNF-␣) [Kikuta et al, 1990;Inagi et al, 1996;Flamand et al, 1991]; and their ability to modulate other immunologically important cell surface molecules (CD3, CD4, and EB1) [Furukawa et al, 1994;Hasegawa et al, 1994] suggest that these viruses may have immunomodulatory potential.…”