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Philos Trans R Soc Lond B Biol Sci. 2001 Apr 29; 356(1408): 421–435.
doi: 10.1098/rstb.2000.0775
PMCID: PMC1088436
PMID: 11313003

Molecular evolution of the gamma-Herpesvirinae.

D J McGeoch
Author information Copyright and License information PMC Disclaimer

Abstract

Genomic sequences available for members of the gamma-Herpesvirinae allow analysis of many aspects of the group's evolution. This paper examines four topics: (i) the phylogeny of the group; (ii) the histories of gamma-herpesvirus-specific genes; (iii) genomic variation of human herpesvirus 8 (HHV-8); and (iv) the relationship between Epstein-Barr virus types 1 and 2 (EBV-1 and EBV-2). A phylogenetic tree based on eight conserved genes has been constructed for eight gamma-herpesviruses and extended to 14 species with smaller gene sets. This gave a generally robust assignment of evolutionary relationships, with the exception of murine herpesvirus 4 (MHV-4), which could not be placed unambiguously on the tree and which has evidently experienced an unusually high rate of genomic change. The gamma-herpesviruses possess a variable complement of genes with cellular homologues. In the clearest cases these virus genes were shown to have originated from host genome lineages in the distant past. HHV-8 possesses at its left genomic terminus a highly diverse gene (K1) and at its right terminus a gene (K15) having two diverged alleles. It was proposed that the high diversity of K1 results from a positive selection on K1 and a hitchhiking effect that reduces diversity elsewhere in the genome. EBV-1 and EBV-2 differ in their alleles of the EBNA-2, EBNA-3A, EBNA-3B and EBNA-3C genes. It was suggested that EBV-1 and EBV-2 may recombine in mixed infections so that their sequences outside these genes remain homogeneous. Models for genesis of the types, by recombination between diverged parents or by local divergence from a single lineage, both present difficulties.

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Selected References

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  • Agius CT, Nagesha HS, Studdert MJ. Equine herpesvirus 5: comparisons with EHV2 (equine cytomegalovirus), cloning, and mapping of a new equine herpesvirus with a novel genome structure. Virology. 1992 Nov;191(1):176–186. [PubMed] [Google Scholar]
  • Albrecht JC. Primary structure of the Herpesvirus ateles genome. J Virol. 2000 Jan;74(2):1033–1037. [PMC free article] [PubMed] [Google Scholar]
  • Albrecht JC, Nicholas J, Biller D, Cameron KR, Biesinger B, Newman C, Wittmann S, Craxton MA, Coleman H, Fleckenstein B, et al. Primary structure of the herpesvirus saimiri genome. J Virol. 1992 Aug;66(8):5047–5058. [PMC free article] [PubMed] [Google Scholar]
  • Alexander L, Denekamp L, Knapp A, Auerbach MR, Damania B, Desrosiers RC. The primary sequence of rhesus monkey rhadinovirus isolate 26-95: sequence similarities to Kaposi's sarcoma-associated herpesvirus and rhesus monkey rhadinovirus isolate 17577. J Virol. 2000 Apr;74(7):3388–3398. [PMC free article] [PubMed] [Google Scholar]
  • Baer R, Bankier AT, Biggin MD, Deininger PL, Farrell PJ, Gibson TJ, Hatfull G, Hudson GS, Satchwell SC, Séguin C, et al. DNA sequence and expression of the B95-8 Epstein-Barr virus genome. Nature. 1984 Jul 19;310(5974):207–211. [PubMed] [Google Scholar]
  • Bhatia K, Raj A, Guitierrez MI, Judde JG, Spangler G, Venkatesh H, Magrath IT. Variation in the sequence of Epstein Barr virus nuclear antigen 1 in normal peripheral blood lymphocytes and in Burkitt's lymphomas. Oncogene. 1996 Jul 4;13(1):177–181. [PubMed] [Google Scholar]
  • Broll H, Finsterbusch T, Buhk HJ, Goltz M. Genetic analysis of the bovine herpesvirus type 4 gene locus for the putative terminase. Virus Genes. 1999;19(3):243–250. [PubMed] [Google Scholar]
  • Cameron KR, Stamminger T, Craxton M, Bodemer W, Honess RW, Fleckenstein B. The 160,000-Mr virion protein encoded at the right end of the herpesvirus saimiri genome is homologous to the 140,000-Mr membrane antigen encoded at the left end of the Epstein-Barr virus genome. J Virol. 1987 Jul;61(7):2063–2070. [PMC free article] [PubMed] [Google Scholar]
  • Cho YG, Gordadze AV, Ling PD, Wang F. Evolution of two types of rhesus lymphocryptovirus similar to type 1 and type 2 Epstein-Barr virus. J Virol. 1999 Nov;73(11):9206–9212. [PMC free article] [PubMed] [Google Scholar]
  • Cook PM, Whitby D, Calabro ML, Luppi M, Kakoola DN, Hjalgrim H, Ariyoshi K, Ensoli B, Davison AJ, Schulz TF. Variability and evolution of Kaposi's sarcoma-associated herpesvirus in Europe and Africa. International Collaborative Group. AIDS. 1999 Jul 9;13(10):1165–1176. [PubMed] [Google Scholar]
  • Dambaugh T, Hennessy K, Chamnankit L, Kieff E. U2 region of Epstein-Barr virus DNA may encode Epstein-Barr nuclear antigen 2. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7632–7636. [PMC free article] [PubMed] [Google Scholar]
  • Davison AJ, Scott JE. The complete DNA sequence of varicella-zoster virus. J Gen Virol. 1986 Sep;67(Pt 9):1759–1816. [PubMed] [Google Scholar]
  • de Campos-Lima PO, Gavioli R, Zhang QJ, Wallace LE, Dolcetti R, Rowe M, Rickinson AB, Masucci MG. HLA-A11 epitope loss isolates of Epstein-Barr virus from a highly A11+ population. Science. 1993 Apr 2;260(5104):98–100. [PubMed] [Google Scholar]
  • Ehlers B, Borchers K, Grund C, Frölich K, Ludwig H, Buhk HJ. Detection of new DNA polymerase genes of known and potentially novel herpesviruses by PCR with degenerate and deoxyinosine-substituted primers. Virus Genes. 1999;18(3):211–220. [PubMed] [Google Scholar]
  • Ensser A, Pflanz R, Fleckenstein B. Primary structure of the alcelaphine herpesvirus 1 genome. J Virol. 1997 Sep;71(9):6517–6525. [PMC free article] [PubMed] [Google Scholar]
  • Goltz M, Broll H, Mankertz A, Weigelt W, Ludwig H, Buhk HJ, Borchers K. Glycoprotein B of bovine herpesvirus type 4: its phylogenetic relationship to gB equivalents of the herpesviruses. Virus Genes. 1994 Sep;9(1):53–59. [PubMed] [Google Scholar]
  • Habeshaw G, Yao QY, Bell AI, Morton D, Rickinson AB. Epstein-barr virus nuclear antigen 1 sequences in endemic and sporadic Burkitt's lymphoma reflect virus strains prevalent in different geographic areas. J Virol. 1999 Feb;73(2):965–975. [PMC free article] [PubMed] [Google Scholar]
  • Hayward GS. KSHV strains: the origins and global spread of the virus. Semin Cancer Biol. 1999 Jun;9(3):187–199. [PubMed] [Google Scholar]
  • Holloway SA, Lindquester GJ, Studdert MJ, Drummer HE. Identification, sequence analysis and characterisation of equine herpesvirus 5 glycoprotein B. Arch Virol. 1999;144(2):287–307. [PubMed] [Google Scholar]
  • Honess RW, Gompels UA, Barrell BG, Craxton M, Cameron KR, Staden R, Chang YN, Hayward GS. Deviations from expected frequencies of CpG dinucleotides in herpesvirus DNAs may be diagnostic of differences in the states of their latent genomes. J Gen Virol. 1989 Apr;70(Pt 4):837–855. [PubMed] [Google Scholar]
  • Ishido S, Wang C, Lee BS, Cohen GB, Jung JU. Downregulation of major histocompatibility complex class I molecules by Kaposi's sarcoma-associated herpesvirus K3 and K5 proteins. J Virol. 2000 Jun;74(11):5300–5309. [PMC free article] [PubMed] [Google Scholar]
  • Ishido S, Choi JK, Lee BS, Wang C, DeMaria M, Johnson RP, Cohen GB, Jung JU. Inhibition of natural killer cell-mediated cytotoxicity by Kaposi's sarcoma-associated herpesvirus K5 protein. Immunity. 2000 Sep;13(3):365–374. [PubMed] [Google Scholar]
  • Jones DT, Taylor WR, Thornton JM. The rapid generation of mutation data matrices from protein sequences. Comput Appl Biosci. 1992 Jun;8(3):275–282. [PubMed] [Google Scholar]
  • Jung JU, Trimble JJ, King NW, Biesinger B, Fleckenstein BW, Desrosiers RC. Identification of transforming genes of subgroup A and C strains of Herpesvirus saimiri. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7051–7055. [PMC free article] [PubMed] [Google Scholar]
  • Kaplan NL, Darden T, Hudson RR. The coalescent process in models with selection. Genetics. 1988 Nov;120(3):819–829. [PMC free article] [PubMed] [Google Scholar]
  • Kaplan NL, Hudson RR, Langley CH. The "hitchhiking effect" revisited. Genetics. 1989 Dec;123(4):887–899. [PMC free article] [PubMed] [Google Scholar]
  • Khanna R, Slade RW, Poulsen L, Moss DJ, Burrows SR, Nicholls J, Burrows JM. Evolutionary dynamics of genetic variation in Epstein-Barr virus isolates of diverse geographical origins: evidence for immune pressure-independent genetic drift. J Virol. 1997 Nov;71(11):8340–8346. [PMC free article] [PubMed] [Google Scholar]
  • Koseki T, Inohara N, Chen S, Carrio R, Merino J, Hottiger MO, Nabel GJ, Núez G. CIPER, a novel NF kappaB-activating protein containing a caspase recruitment domain with homology to Herpesvirus-2 protein E10. J Biol Chem. 1999 Apr 9;274(15):9955–9961. [PubMed] [Google Scholar]
  • Kumar S, Hedges SB. A molecular timescale for vertebrate evolution. Nature. 1998 Apr 30;392(6679):917–920. [PubMed] [Google Scholar]
  • Lacoste V, Mauclère P, Dubreuil G, Lewis J, Georges-Courbot MC, Gessain A. KSHV-like herpesviruses in chimps and gorillas. Nature. 2000 Sep 14;407(6801):151–152. [PubMed] [Google Scholar]
  • Lee SP, Morgan S, Skinner J, Thomas WA, Jones SR, Sutton J, Khanna R, Whittle HC, Rickinson AB. Epstein-Barr virus isolates with the major HLA B35.01-restricted cytotoxic T lymphocyte epitope are prevalent in a highly B35.01-positive African population. Eur J Immunol. 1995 Jan;25(1):102–110. [PubMed] [Google Scholar]
  • Lee H, Veazey R, Williams K, Li M, Guo J, Neipel F, Fleckenstein B, Lackner A, Desrosiers RC, Jung JU. Deregulation of cell growth by the K1 gene of Kaposi's sarcoma-associated herpesvirus. Nat Med. 1998 Apr;4(4):435–440. [PubMed] [Google Scholar]
  • Lees JF, Arrand JE, Pepper SD, Stewart JP, Mackett M, Arrand JR. The Epstein-Barr virus candidate vaccine antigen gp340/220 is highly conserved between virus types A and B. Virology. 1993 Aug;195(2):578–586. [PubMed] [Google Scholar]
  • McGeoch DJ, Cook S. Molecular phylogeny of the alphaherpesvirinae subfamily and a proposed evolutionary timescale. J Mol Biol. 1994 Apr 22;238(1):9–22. [PubMed] [Google Scholar]
  • McGeoch DJ, Davison AJ. The descent of human herpesvirus 8. Semin Cancer Biol. 1999 Jun;9(3):201–209. [PubMed] [Google Scholar]
  • McGeoch DJ, Cook S, Dolan A, Jamieson FE, Telford EA. Molecular phylogeny and evolutionary timescale for the family of mammalian herpesviruses. J Mol Biol. 1995 Mar 31;247(3):443–458. [PubMed] [Google Scholar]
  • MacKenzie J, Gray D, Pinto-Paes R, Barrezueta LF, Armstrong AA, Alexander FA, McGeoch DJ, Jarrett RF. Analysis of Epstein-Barr virus (EBV) nuclear antigen 1 subtypes in EBV-associated lymphomas from Brazil and the United Kingdom. J Gen Virol. 1999 Oct;80(Pt 10):2741–2745. [PubMed] [Google Scholar]
  • Meng YX, Spira TJ, Bhat GJ, Birch CJ, Druce JD, Edlin BR, Edwards R, Gunthel C, Newton R, Stamey FR, et al. Individuals from North America, Australasia, and Africa are infected with four different genotypes of human herpesvirus 8. Virology. 1999 Aug 15;261(1):106–119. [PubMed] [Google Scholar]
  • Midgley RS, Blake NW, Yao QY, Croom-Carter D, Cheung ST, Leung SF, Chan AT, Johnson PJ, Huang D, Rickinson AB, et al. Novel intertypic recombinants of epstein-barr virus in the chinese population. J Virol. 2000 Feb;74(3):1544–1548. [PMC free article] [PubMed] [Google Scholar]
  • Neipel F, Fleckenstein B. The role of HHV-8 in Kaposi's sarcoma. Semin Cancer Biol. 1999 Jun;9(3):151–164. [PubMed] [Google Scholar]
  • Neipel F, Albrecht JC, Fleckenstein B. Cell-homologous genes in the Kaposi's sarcoma-associated rhadinovirus human herpesvirus 8: determinants of its pathogenicity? J Virol. 1997 Jun;71(6):4187–4192. [PMC free article] [PubMed] [Google Scholar]
  • Nicholas J, Zong JC, Alcendor DJ, Ciufo DM, Poole LJ, Sarisky RT, Chiou CJ, Zhang X, Wan X, Guo HG, et al. Novel organizational features, captured cellular genes, and strain variability within the genome of KSHV/HHV8. J Natl Cancer Inst Monogr. 1998;(23):79–88. [PubMed] [Google Scholar]
  • Parker BD, Bankier A, Satchwell S, Barrell B, Farrell PJ. Sequence and transcription of Raji Epstein-Barr virus DNA spanning the B95-8 deletion region. Virology. 1990 Nov;179(1):339–346. [PubMed] [Google Scholar]
  • Peng R, Gordadze AV, Fuentes Pananá EM, Wang F, Zong J, Hayward GS, Tan J, Ling PD. Sequence and functional analysis of EBNA-LP and EBNA2 proteins from nonhuman primate lymphocryptoviruses. J Virol. 2000 Jan;74(1):379–389. [PMC free article] [PubMed] [Google Scholar]
  • Poole LJ, Zong JC, Ciufo DM, Alcendor DJ, Cannon JS, Ambinder R, Orenstein JM, Reitz MS, Hayward GS. Comparison of genetic variability at multiple loci across the genomes of the major subtypes of Kaposi's sarcoma-associated herpesvirus reveals evidence for recombination and for two distinct types of open reading frame K15 alleles at the right-hand end. J Virol. 1999 Aug;73(8):6646–6660. [PMC free article] [PubMed] [Google Scholar]
  • Rickinson AB, Young LS, Rowe M. Influence of the Epstein-Barr virus nuclear antigen EBNA 2 on the growth phenotype of virus-transformed B cells. J Virol. 1987 May;61(5):1310–1317. [PMC free article] [PubMed] [Google Scholar]
  • Rivailler P, Quink C, Wang F. Strong selective pressure for evolution of an Epstein-Barr virus LMP2B homologue in the rhesus lymphocryptovirus. J Virol. 1999 Oct;73(10):8867–8872. [PMC free article] [PubMed] [Google Scholar]
  • Rovnak J, Quackenbush SL, Reyes RA, Baines JD, Parrish CR, Casey JW. Detection of a novel bovine lymphotropic herpesvirus. J Virol. 1998 May;72(5):4237–4242. [PMC free article] [PubMed] [Google Scholar]
  • Ruf IK, Moghaddam A, Wang F, Sample J. Mechanisms that regulate Epstein-Barr virus EBNA-1 gene transcription during restricted latency are conserved among lymphocryptoviruses of Old World primates. J Virol. 1999 Mar;73(3):1980–1989. [PMC free article] [PubMed] [Google Scholar]
  • Sample J, Young L, Martin B, Chatman T, Kieff E, Rickinson A, Kieff E. Epstein-Barr virus types 1 and 2 differ in their EBNA-3A, EBNA-3B, and EBNA-3C genes. J Virol. 1990 Sep;64(9):4084–4092. [PMC free article] [PubMed] [Google Scholar]
  • Schultz ER, Rankin GW, Jr, Blanc MP, Raden BW, Tsai CC, Rose TM. Characterization of two divergent lineages of macaque rhadinoviruses related to Kaposi's sarcoma-associated herpesvirus. J Virol. 2000 May;74(10):4919–4928. [PMC free article] [PubMed] [Google Scholar]
  • Searles RP, Bergquam EP, Axthelm MK, Wong SW. Sequence and genomic analysis of a Rhesus macaque rhadinovirus with similarity to Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8. J Virol. 1999 Apr;73(4):3040–3053. [PMC free article] [PubMed] [Google Scholar]
  • Snudden DK, Smith PR, Lai D, Ng MH, Griffin BE. Alterations in the structure of the EBV nuclear antigen, EBNA1, in epithelial cell tumours. Oncogene. 1995 Apr 20;10(8):1545–1552. [PubMed] [Google Scholar]
  • Telford EA, Watson MS, Aird HC, Perry J, Davison AJ. The DNA sequence of equine herpesvirus 2. J Mol Biol. 1995 Jun 9;249(3):520–528. [PubMed] [Google Scholar]
  • Thome M, Martinon F, Hofmann K, Rubio V, Steiner V, Schneider P, Mattmann C, Tschopp J. Equine herpesvirus-2 E10 gene product, but not its cellular homologue, activates NF-kappaB transcription factor and c-Jun N-terminal kinase. J Biol Chem. 1999 Apr 9;274(15):9962–9968. [PubMed] [Google Scholar]
  • Triantos D, Boulter AW, Leao JC, Di Alberti L, Porter SR, Scully CM, Birnbaum W, Johnson NW, Teo CG. Diversity of naturally occurring Epstein-Barr virus revealed by nucleotide sequence polymorphism in hypervariable domains in the BamHI K and N subgenomic regions. J Gen Virol. 1998 Nov;79(Pt 11):2809–2817. [PubMed] [Google Scholar]
  • Ulrich S, Goltz M, Ehlers B. Characterization of the DNA polymerase loci of the novel porcine lymphotropic herpesviruses 1 and 2 in domestic and feral pigs. J Gen Virol. 1999 Dec;80(Pt 12):3199–3205. [PubMed] [Google Scholar]
  • van Santen VL. Characterization of the bovine herpesvirus 4 major immediate-early transcript. J Virol. 1991 Oct;65(10):5211–5224. [PMC free article] [PubMed] [Google Scholar]
  • Vanderplasschen A, Markine-Goriaynoff N, Lomonte P, Suzuki M, Hiraoka N, Yeh JC, Bureau F, Willems L, Thiry E, Fukuda M, et al. A multipotential beta -1,6-N-acetylglucosaminyl-transferase is encoded by bovine herpesvirus type 4. Proc Natl Acad Sci U S A. 2000 May 23;97(11):5756–5761. [PMC free article] [PubMed] [Google Scholar]
  • Virgin HW, 4th, Latreille P, Wamsley P, Hallsworth K, Weck KE, Dal Canto AJ, Speck SH. Complete sequence and genomic analysis of murine gammaherpesvirus 68. J Virol. 1997 Aug;71(8):5894–5904. [PMC free article] [PubMed] [Google Scholar]
  • Wrightham MN, Stewart JP, Janjua NJ, Pepper SD, Sample C, Rooney CM, Arrand JR. Antigenic and sequence variation in the C-terminal unique domain of the Epstein-Barr virus nuclear antigen EBNA-1. Virology. 1995 Apr 20;208(2):521–530. [PubMed] [Google Scholar]
  • Yang Z. PAML: a program package for phylogenetic analysis by maximum likelihood. Comput Appl Biosci. 1997 Oct;13(5):555–556. [PubMed] [Google Scholar]
  • Yates JL, Camiolo SM, Ali S, Ying A. Comparison of the EBNA1 proteins of Epstein-Barr virus and herpesvirus papio in sequence and function. Virology. 1996 Aug 1;222(1):1–13. [PubMed] [Google Scholar]
  • Zimber U, Adldinger HK, Lenoir GM, Vuillaume M, Knebel-Doeberitz MV, Laux G, Desgranges C, Wittmann P, Freese UK, Schneider U, et al. Geographical prevalence of two types of Epstein-Barr virus. Virology. 1986 Oct 15;154(1):56–66. [PubMed] [Google Scholar]
  • Zong JC, Ciufo DM, Alcendor DJ, Wan X, Nicholas J, Browning PJ, Rady PL, Tyring SK, Orenstein JM, Rabkin CS, et al. High-level variability in the ORF-K1 membrane protein gene at the left end of the Kaposi's sarcoma-associated herpesvirus genome defines four major virus subtypes and multiple variants or clades in different human populations. J Virol. 1999 May;73(5):4156–4170. [PMC free article] [PubMed] [Google Scholar]
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