Advances in gene encoding proteins of human herpesvirus 6

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1 Journal of Microbes and Infection, September 2009, Vol. 4, No , 2 1., ; 2., : 6 ( HHV-6) DNA, HHV , ( IE) DNA DNA HHV-6 : 6 ; ; Advances in gene encoding proteins of human herpesvirus 6 JIANG Lan-Lan 1, YAO Kun 2 1. Wuhu Second People s Hospital, Wuhu , China; 2. Department of Microbiology and Immunology, Nanjing Medical University, Nanjing , China Abstract: Human herpesvirus 6 ( HHV-6), a double-stranded DNA virus, is a member of the herpes subfamily. It has been hypothesized that the HHV-6 genome may code 80 to 100 different proteins, including membrane proteins, immediate early ( IE) proteins, DNA packaging proteins, and virus assembly proteins, etc. In this article, the research progress regarding the features and functions of proteins encoded by the HHV-6 gene is reviewed. Key words: Human herpesvirus 6; Gene encoding proteins; Features and functions of proteins 6 ( human herpesvirus 6, HHV-6) T DNA, 1986 ( acquired immunodeficiency syndrome, AIDS), HHV-6 HHV-6, HHV-6A HHV-6B HHV-6A GS U1102, HHV-6B Z29, A B 96%, HHV-6, ( immediate early, IE) HHV-6 1 HHV-6 HHV-6 DNA, kb, 3, ( unique long region, UL ), 1 ( DRL DRR ) HHV ( open reading frame, ORF), UL 100, DRL DRR 8, 102 ORF, P100 IE gh HHV-6 40, DNA 2 HHV-6 HHV , : ( ) :, yaokun@ njmu. edu. cn Corresponding author: YAO Kun, yaokun@ njmu. edu. cn IE DNA DNA, IE

2 Journal of Microbes and Infection, September 2009, Vol. 4, No HHV-6 U39 U48 gb gh,,, gb, gh, U82 gl, gh gh-gl, gh, gl gh, gh gb gh-gl U18 ( human immunodeficiency virus type 1, HIV-1) AIDS HHV-6 HIV, HIV, HIV, HIV AIDS [ 1] HHV-6 U83 vccl4 18 CCL2 CCR2, vccl4 HHV-6 CCR2, CCR2 CCR2, HHV-6, vccl4 CCR2 [ 2 ] U12,, HHV-6 HHV-6 U51 G, RANTES, RANTES, ; [ 3 ] U72, gm, ( herpes simplex virus, HSV) gm,, HHV-6A U100 4, gp82 /105 gq( /74 000) gp82 /105 HHV-6,,, HHV-6A gq( ) gh-gl gh-gl-gq, CD46, gh-gl-gq CD46, CD46, HHV- 6A gh-gl-gq-80k [ 4, 5 ] HHV-6B UL47 go, gl HHV-6B 2 go gl EB ( Epstein-Barr virus, EBV) gh-gl-gp42 ; ( cytomegalovirus, CMV) gh-gl-go ; HHV-6B go gl, [ 6] go gl 20 h, 3 4 d,, go gl, 96 h, 1 [ 7, 8] 2. 2 IE IE, HHV-6 7, DR7 U16 /U17 U18 /U19 U27 U86 /U87 U89 U94 HHV-6 U18 R1 ( human cytomegalovirus, HCMV) IE2, RNA, RNA ; U89 / U90 U91 IE, U91 HHV-6 DR7,, p53, p53 HHV-6 P53, CK2 P38 P53, HHV-6 [ 9, 10 ] 2. 3 DNA, U27

3 Journal of Microbes and Infection, September 2009, Vol. 4, No ,, DNA HHV-6 7, DNA DNA - ( odorantbinding protein, OBP), HHV-6 HHV-6 U38 DNA, DNA ; U73 DNA, 1 ; U94, ( adeno-associated virus Rep protein, AAV-rep), AAV-rep, DNA, mrna H-ras HIV DNA DNA HHV-6 U53 /, DNA, HHV-6 U29 U30 U60 /U66 DNA U11 P100 HHV-6, gh gl, gh, gh HHV-6 HHV-6 P100, P100 HHV-6, HHV-6 [ 11 ] 3 HHV-6 HHV-6, 1, HHV-6 HHV-6 CD4 + T, CD8 + T CD4, CD4 ; CD46 HHV-6, HHV-6A gh-gl-gq-80k, gh-gl CD46, gh-gl CD46 HHV-6 gq-80k CD46,, HHV-6A HHV-6B,, CD46 FFWO CD46 SCR2 SCR3 SCR4, SCR2 SCR3 HHV-6 [ 6, 12 ] 4 HHV-6 HHV-6,, T ( regulatory T cell, Treg) Treg T, [ 13, 14 ] ( hepatitis C virus, HCV) EBV HIV CD4 + Treg HHV-6 HHV-6 CD4 + T HHV-6 10 ( interleukin-10, IL-10) CD4 + T, Tr1, IL-10 [ 15],,, HHV-6, HHV-6 CD4 + HHV-6 HCMV 27% 51%, 2 6, 6 CD4 + HHV-6 HIV CD4 + T T, T, HHV-6 US22 HIV ( long terminal repeat, LTR), HIV, CD4 + T HHV-6 HIV CD8 + CD4 - T, CD4 + T mrna CD4, HIV, HIV HHV-6 ( interferon, IFN- ) ( tumor necrosis factor-, TNF- ) IL-1, AIDS, HHV-6 HIV CCR5

4 Journal of Microbes and Infection, September 2009, Vol. 4, No. 3, CXCR4, CCR5 T RANTES, HIV [ 16-18] 5 HHV-6,, HHV-6, HHV-6, [ ], HHV-6 HHV-6, HHV-6 IE DNA DNA, HHV-6, [ 1] Leach CT, Pollock BH, McClain KL, et al. Human herpesvirus 6 and cytomegalovirus infections in children with human immunodeficiency virus infection and cancer [ J]. Pediatr Infect Dis, 2002, 21( 2) : [ 2] L ttichau HR, Clark-Lewis I, Jensen P, et al. A highly selective CCR2 chemokine agonist encoded by human herpesvirus 6 [ J]. J Biol Chem, 2003, 278 ( 13) : [ 3] Milne RS, Mattick C, Nicholson L, et al. RANTES binding and down-regulation by a novel human herpesvirus 6 beta-chemokine receptor[ J]. J Immunol, 2000, 164( 5) : [ 4] Mori Y, Seya T, Huang HL, et al. Human herpesvirus 6 variant A but not variant B induces fusion from without in a variety of human cells through a human herpesvirus 6 entry receptor CD46[ J]. J Virol, 2002, 76 ( 13) : [ 5] Mori Y, Yang X, Akkapaiboon P, et al. Human herpesvirus 6 variant A glycoprotein H-glycoprotein L- glycoprotein Q complex associates with human CD46 [ J]. J Virol, 2003, 77( 8) : [ 6] Mori Y, Dhepakson P, Shimamoto T, et al. Expression of human herpesvirus 6B rep within infected cells and binding of its gene product to the TATA- binding protein in vitro and in vivo[ J]. J Virol, 2000, 74( 13) : [ 7] Akkapaiboon P, Mori Y, Sadaoka T, et al. Intracellular processing of human herpes virus 6 glycoproteins Q1 and Q2 into tetrameric complexes expressed on the viral envelope[ J]. J Virol, 2004, 78( 15) : [ 8],,,. -6B go gl [ J]., 2006, 16( 6) : [ 9] Oster B, Kaspersen MD, Kofod-Olsen E, et al. Human herpesvirus 6B inhibits cell proliferation by a p53- independent pathway [ J]. J Clin Virol, 2006, 37 ( Suppl 1) : S63-S68 [ 10] Oster B, Bundgaard B, Hupp TR, et al. Human herpesvirus 6B induces phosphorylation of p53 in its regulatory domain by a CK2- and p38-independent pathway[ J]. J Gen Virol, 2008, 89( Pt 1) : [ 11] Pellett PE, S nchez-mart nez D, Dominguez G, et al. A strongly immunoreactive virion protein of human herpesvirus 6 variant B strain Z29: identification and characterization of the gene and mapping of a variantspecific monoclonal antibody reactive epitope [ J]. Virology, 1993, 195( 2) : [ 12] Mori Y, Akkapaiboon P, Yang X, et al. The human herpesvirus 6 U100 gene product is the third component of the gh-gl glycoprotein complex on the viral envelope [ J]. J Virol, 2003, 77( 4) : [ 13] Pakravan N, Hassan AT, Hassan ZM. Naturally occurring self-reactive CD4 + CD25 + regulatory T cells: universal immune code[ J]. Cell Mol Immunol, 2007, 4 ( 3) : [ 14] Raimondi G, Turner MS, Thomson AW, et al. Naturally occurring regulatory T cells: recent insights in health and disease[ J]. Crit Rev Immunol, 2007, 27( 1) : [ 15] Wang F, Yao K, Yin QZ, et al. Human herpesvirus-6- specific interleukin 10-producing CD4 + T cells suppress the CD4 + T-cell response in infected individuals[ J]. Microbiol Immunol, 2006, 50( 10) : [ 16] Salahuddin SZ, Snyder KA, Godwin A, et al. The simultaneous presence and expression of human hepatitis C virus ( HCV), human herpesvirus-6 ( HHV-6), and human immunodeficiency virus-1 ( HIV-1) human T-cell[ J]. Virol J, 2007, 4: 106 in a single [ 17] Lusso P, Crowley RW, Malnati MS, et al. Human herpesvirus 6A accelerates AIDS progression in macaques[ J]. Proc Natl Acad Sci USA, 2007, 104( 12) :

5 Journal of Microbes and Infection, September 2009, Vol. 4, No [ 18] Grivel JC, Ito Y, Faga G, et al. Suppression of CCR5- but not CXCR4-tropic HIV-1 in lymphoid tissue by human herpesvirus 6 [ J]. Nat Med, 2001, 7 ( 11 ) : [ 19] Nagasawa T, Kimura I, Abe Y, et al. HHV-6 encephalopathy with cluster of convulsions during eruptive stage[ J]. Pediatr Neurol, 2007, 36( 1) : [ 20] Chamberlain MC, Chowdhary S. Post-transplant acute limbic encephalitis: clinical features and relationship to HHV-6[ J]. Neurology, 2008, 70( 6) : [ 21] Loginov R, H rm M, Halme L, et al. HHV-6 DNA in peripheral blood mononuclear cells after liver transplantation[ J]. J Clin Virol, 2006, 37 ( Suppl 1) : S76-S81 [ 22] Yamane A, Mori T, Suzuki S, et al. Risk factors for developing human herpesvirus 6 ( HHV-6) reactivation after allogeneic hematopoietic stem cell transplantation and its association with central nervous system disorders [ J]. Biol Blood Marrow Transplant, 2007, 13( 1) : [ 23] De Filippis L, Foglieni C, Silva S, et al. Differentiated human neural stem cells: a new ex vivo model to study HHV-6 infection of the central nervous system[ J]. J Clin Virol, 2006, 37 ( Suppl 1) : S27-S32 ( : )

Herpesviruses. Virion. Genome. Genes and proteins. Viruses and hosts. Diseases. Distinctive characteristics

Herpesviruses. Virion. Genome. Genes and proteins. Viruses and hosts. Diseases. Distinctive characteristics Herpesviruses Virion Genome Genes and proteins Viruses and hosts Diseases Distinctive characteristics Virion Enveloped icosahedral capsid (T=16), diameter 125 nm Diameter of enveloped virion 200 nm Capsid