疱 herpesviruses DNA capsid 疱 疱 疱 疱 疱 herpes simplex virus 1 HSV-1 疱 herpes simplex virus 2 HSV-2 疱 varicella-zoster virus VZV EB Epstein-Barr virus EBV human cytomegalovirus HCMV 疱 human herpesvirus 6 HHV6 疱 human herpesvirus 7 HHV7 (Levy, 1997; Roizman, 1996) 疱 HHV8 1995 (Moore and Chang, 1995) (Levy, 1997; Memar et al., 1995) 1
DNA mrna (Bresnahan and Shenk, 2000) 疱 linear double-stranded DNA DNA (Roizman, 1996) 疱 120 kb 230 kb DNA 疱 DNA direct repeat inverted repeat (Roizman, 1996) 疱 DNA 疱 疱 EB 疱 疱 疱 2
疱 Cytomegalovirus CMV 疱 β- 疱 (Roizman, 1996) 疱 β- 疱 (Edward and Mocarski, 1996) (Stinski, 1991) productive infection simian CMV SCMV 1978 encephalopathy strain Colburn fibroblast (Huang et al., 1978) (Huang and Kowalik, 1993) 40% 100% (Macias et al., 1996) 3
13% 15% (Alexander, 1967) 15% (Huang and Kowalik, 1993) cytomegaly inclusion (Edward and Mocarski, 1996; Huang and Kowalik, 1993) 疱 perfusion (Britt and Alford, 1996; Huang and Kowalik, 1993) 1990 AD169 strain X17403 (Chee et al., 1990a) DNA 229354 bp G C 57% 200 (Chee et al., 1990a) 1 post-translational modification (Stinski, 1991) DNA 4
UL US terminal repetitive sequence TR internal repetitive sequence IR TRL UL IRL IRS TRS L component S component DNA quiescent persistent productive (Edward and Mocarski, 1996; Huang and Kowalik, 1993) immediate-early IE early E late L (i) mrna (ii) (iii) 5
24 hr 48 hr 72 hr 0 hr α β β1 β2 γ1 γ2 L γ (1) IE α IE IE transcriptional regulation IE major IE promoter MIEP (2) E β β1 β2 β1 β2 DNA (3) L γ γ1 γ2 γ1 6
γ2 assembly DNA (Huang and Kowalik, 1993) cellular receptor glycoprotein gb gh transcription factor NF-κB Sp-1 AP1 IE promoter IE repressor IE E epithelial endothelial fibroblast (Edward and Mocarski, 7
1996) foreskin fibroblast (Stenberg et al., 1989) 2,500 3,000 human umbilical vein endothelial cell HUVEC sodium butyrate (Mocarski, 1991) (Roizman, 2000) (1) β-2 β-2 microglobulin β-2 MHC I β-2 tegument (Grundy et al., 1987) β-2 UL18 (Beck and Barrell, 1988) (2) G- G protein-coupled receptor family UL33 US27 US28 (Chee et al., 1990b) (3) gh HCMV UL75 gb HCMV UL55 8
90-kDa 30-kDa (Mocarski, 1991) internalize (Huang and Kowalik, 1993) mental retardation mononucleosis chorioretinitis interstitial pneumonitis AIDS (Friedman et al., 1982; Spector et al., 1984) AIDS prognosis HIV LTR(Barry et al., 1990; Davis et al., 1987; Duclos et al., 1989; Hagemeier et al., 1992a) AIDS reactivation (Huang and Kowalik, 1993) (Myers et al., 1975) 9
IE IE E L IE IE 1 UL123 UL122 1 UL36 UL37 UL38 UL69 US3 IRS1 TRS1 MIEP 2 IE enhancer cis-regulating element MIEP tissue-specific (Baskar JF, 1996) MIEP (Boshart et al., 1985; Chiou et al., 2001) MIEP 10
MIEP IE RNA (Huang and Kowalik, 1993; Huang et al., 1994; Speir et al., 1994) IE post-transcriptional regulation E L IE RNA IE RNA 3 IE RNA IE RNA IE RNA polysome IE RNA (Stenberg et al., 1989) MIEP permissive non-permissive (Huang and Kowalik, 1993) MIEP binding site nuclear factor 1 NF1 (Hennighausen and Fleckenstein, 1986) CCAAT binding factor CBF Sp-1(Lang et al., 1992; Wu et al., 1998) AP1 NF-κB repeat sequence 2 (Edward and Mocarski, 1996; 11
Fickenscher et al., 1989; Mach et al., 1989) MIE MIEP IE1-72 IE2-55 (Baracchini et al., 1992; Cherrington and Mocarski, 1989; Stenberg et al., 1990) MIEP IE2-86 MIEP (Stenberg et al., 1990) 3 IE1 72 KDa IE1-72 IE1-72 IE exon 1 ~ exon 4 1741 苷 491 (Stenberg et al., 1984) IE1-72 IE2 E E promoter (Cherrington and Mocarski, 1989; Stenberg et al., 1989) NF-κB NF-κB GGGACTTTCC (Mocarski, 1991) IE1-72 RNA IE RNA (Blanton and Tevethia, 1981; Stenberg and Stinski, 1985) IE1-72 IE1-72 RNA (Stenberg et al., 1989) IE2 IE1 DNA (Stenberg et al., 1985) IE2 12
IE2-86 exon 1 ~ exon 3 IE1-72 exon 5 IE2-86 1 85 IE2-86 methionine 85 IE1-72 IE2-86 579 IE1-72 IE (Blanton and Tevethia, 1981; Edward and Mocarski, 1996) L DNA (Stenberg et al., 1989) IE2 IE1 IE2 IE IE2 RNA 1.1 kb 2.2 kb (Stinski et al., 1983) IE2 RNA (Stenberg et al., 1989; Stenberg et al., 1985) 86 KDa IE2-86 55 KDa IE2-55 18 KDa IE2-18 N IE2-86 IE1-72 85 (Stenberg et al., 1989; Stenberg et al., 1985) γie2 IE2 γie2 IE2-86 C 338 40 KDa L (Puchtler and Stamminger, 1991; Stenberg et al., 1989) 13
IE MIEP E 4 (Huang and Kowalik, 1993) IE IE1-72 IE2-86 (Britt and Alford, 1996; Wu et al., 1998) IE2-86 DNA (Arlt et al., 1994; Caswell et al., 1993; Jupp et al., 1993b; Lang et al., 1992; Scheartz et al., 1994; Spector and Tevethia, 1994; Wu et al., 1993) IE2-86 DNA minor groove IE2-86 DNA (Ahn et al., 1998; Lang and Stamminger, 1994; Wu et al., 1998) IE2-86 IE2-86 579 (Ahn et al., 1998; Caswell et al., 1993; Lang et al., 1995) 14
1 100 200 300 400 500 579 1 98 195 579 Activation 290 TBP binding 290 TFIIB binding 290 CREB binding c-jun binding DNA binding 3 46 291 369 3 dimer 88 410 504 542 542 579 IE2-86 DNA IE2-86 CASTing(Funk et al., 1992; Funk and Wright, 1992; Ouellette et al., 1992; Wright et al., 1991) SAAB(Blackwell et al., 1990; Blackwell and Weintraub, 1990; Rice et al., 1984) IE2-86 DNA IE2-86 IE2-86 15