Perinatal cytomegalovirus infections u Kei NUMAZAKI HCMV 1 HCMV HCMV 2, 3 HCMV HCMV HCMV 6 HHV-6 7 HHV-7 5 HHV-5 DNA HCMV 200 300nm 227 235Kb 165 lower matrix phosphoprotein 65 pp65 unique long 83 UL83 UL82 virion transactivator pp71 upper matrix proteinul32 herpesvirus core virion maturation protein pp150 large matrix proteinul48 largest tegment proteinul99-encoded pp28 2 glycoprotein B gbgh gl gm gn go gb 4 HCMV gb gh HCMV II CD13 N α PDGFR-α HCMV PDGFR-α HCMV 2 PDGFRα IMC-3G3 HCMV VP16 immediate early, IEIE IE1 IE2 Early delayed-early, Elate, L 0329-3763 537-3 numazaki@iuhw.ac.jp Professor & Chair, Division of International Infectious Diseases, Graduate School, Departments of Pediatrics and Infection Control, University Hospital International University of Health and Welfare (537-3, Iguchi, Nasusiobara, Tochigi)
α 5 IE IE1 IE2 DNA DNA IE1 1E2 IE1 NF-kB IE2 24 Late L DNA 2 DNA 1 L HCMV RNA IE abortive infection DNA IE CD14 0.01 HCMV dendritic cell : DC HCMV HCMV MIEP major immediateearly promoter HP1 heterchromatin protein 1 HP1 HCMV HCMV CMV CD8T HCMV HCMV HCMV NK HCMV HCMV HCMV HCMV 1990 HCMV 90 3 HCMV HCMV 4,000 0.29 0.48 0.2 2.0 40,000 HCMV 5 7 HCMV 10 15 HCMV 40 50 10 8 10 HCMV 0.5 2.0 8, 9 HCMV cytomegalic inclusion disease, CID HCMV
HCMV. 1 CT. 5 MRI HCMV u 1977 1981 1982 1985 1986 1990 1991 1996 1997 2002 3,084 2,814 2,097 1,898 2,045 14 0.45 10 0.36 7 0.33 3 0.16 3 0.15 1977 2002 11,938 37 0.31 1 0.032 1 0.036 1 0.048 1 0.053 1 0.049 5 0.042 MRC-5 HCMV sensorineural hearing loss, SNHL CID HCMV MRI T1, T2 28 10 12 Boppana 11 HCMV HCMV 13 1977 2002 11,938 1 MRC-5 HCMV IE E 11,938 37 0.31 CMV 5 32 1977 1981 0.451982 1985 0.361986 1990 0.331991 1996 0.161997 2002 0.15 0.0320.0360.0480.0530.049 13 HCMV 7 21 2
HCMV CD4 T IFN- TNF- α 14 HCMV mrna NASBA nucleic acid sequence based amplification antigenemia DNA PCR IgM mrna HCMV 1,000 5,000 Antigenemia 2 C7HRP C10C11 HCMV Hagay 15 HCMV IgM HCMV 1 2 HCMV 20 HCMV HCMV IgM in situ hybridization ISH HCMV u 1. 1 2 IgM CT MRIABR 2. 1 CMV 2 ELISA IF CMV IgM 3 HCMV 16 DNA HCMV sil-2r 17 19 HCMV in vitro HCMV ganciclovir, GCV, dihdroxy propoxymethyl guanine, DHPGfoscarnet, sodium phosphonoformate HCMV HCMV TK HCMV HCMV GCV Whitley 20 HCMV GCV GCV 12mg kg day 6
200mg kg day 1 1 2 GCV GCV HCMV GCV DNA polymerase 1 5mg kg 1 2 1 14 1 6mg kg 5 1 5mg kg 7 1 HCMV HCMV DNA 200 U kg HCMV NK HLA DR tumor necrosis factor TNF avidity NK HLA DR 21 23 HCMV prophylactic therapy, pre-emptive therapy preemptive therapy GCV GCV HCMV HIV HCMV GCV AIDS HCMV DNA polymerase GCV 1 60mg kg 1 3 8 1 1 90mg kg 1 2 12 2 14 21 90 120mg kg 2 1 1 1 250mg 12 6 0.4mlkg HCMV CTL in vitro donor leukocyte transfusion DLT HCMV 24 HCMV 25 HCMV 26
MF59 HCMV B 27 1 HCMV 0 1 6 3 HCMV IgG 3 42 HCMV 1 49 18 31 42 P 0.02 HCMV 1 3 HCMV B HCMV HCMV HCMV HCMV 1 Numazaki K. Current concepts of management for congenital cytomegalovirus infection. Trends in Developmental Biology, : 1-11, 2007. 2 Numazaki K. Immunological evaluation of children with congenital cytomegalovirus infection and infected women during pregnancy. Current Trends in Immunology, : 45-54, 2003. 3 Numazaki K, Fujikawa T : Prevalence of serum antibodies to cytomegalovirus in pregnant women in Sapporo, Japan. Int J Infect Dis, : 147-148, 2002. 4 Tanaka K, Numazaki K, Tsutsumi H : Human cytomegalovirus genetic variability in strains isolated from Japanese children during 1983-2003. J Med Virol, : 356-360, 2005. 5 Duff P. Cytomegalovirus infection in pregnancy. Infect Dis Obstet Gynecol, : 146-152, 1994. 6 Lipitz S, Yagel S, Shalev E, Achiron R, Mashiach S, Schiff E. Prenatal diagnosis of fetal primary cytomegalovirus infection. Obstet Gynecol, : 763-767, 1997. 7 Azam AZ, Vial Y, Fawer CL, Zufferey J, Hohlfeld P. Prenatal diagnosis of congenital cytomegalovirus infection. Obstet Gynecol, : 443-448, 2001. 8 Boppana SB, Rivera LB, Fowler KB, Mach M, Britt WJ. Intrauterine transmission of cytomegalovirus to infants of women with preconceptional immunity. N Engl J Med, : 1366-1371, 2001. 9 Fowler KB, Stagno S, Pass RF. Maternal immunity and prevention of congenital cytomegalovirus infection. JAMA, : 1008-1011, 2003. 10 Boppana SB, et al : Symptomatic congenital cytomegalovirus infection in infants born to mothers with preexisting immunity to cytomegalovirus. Pediatrics, : 55, 1999. 11 Boppana SB, Britt WJ : Antiviral antibody responses and intrauterine transmission after primary maternal cytomegalovirus infection. J Infect Dis : 1115-1121, 1995. 12 Fowler KB, Stagno S, Pass RF, Britt WJ, Boll TJ, Alford CA. The outcome of congenital cytomegalovirus infection in relation to maternal antibody status. N Engl J Med, : 663-667, 1992. 13 Numazaki K, Fujikawa T : Chronological changes of incidence and prognosis of children with asymptomatic congenital cytomegalovirus infection in Sapporo, Japan. BMC Infect Dis, : 22 1-5, 2004. 14 Numazaki K, Fujikawa T, Asanuma H : Immunological evaluation and clinical aspects of children with congenital cytomegalovirus infection. Congenital Anomalies, : 181-186, 2002. 15 Hagay ZJ, et al : Congenital cytomegalovirus infection : a long-standing problem still seeking a solution. Am J Obstet Gynecol, : 241-245, 1996. 16 Balcarek KB, et al : Neonatal screening for congenital cytomegalovirus infection by detection of virus in saliva. J Infect. Dis, : 1433-1436, 1993. 17 Numazaki K, Asanuma H, Ikehata M, Chiba S : Detection of cytokines and cytomegalovirus DNA in serum as test for congenital infection. Ear Hum Dev, : 43-48, 1998. 18 Fujikawa T, Numazaki K, Asanuma H, Tsutsumi H : Human cytomegalovirus infection during pregnancy and detection of specific T cells by intracellular cytokine staining. Int J Infect Dis, : 215-221, 2003.
19 Fujikawa T, Numazaki K, Asanuma H, Kudo R, Tsutsumi H : Frequency of human cytomegalovirus-specific T cells during pregnancy determined by intracellular cytokine staining. J Med Virol, : 527-531, 2003. 20 Whitley RJ, et al : Ganciclovir treatment of symptomatic congenital cytomegalovirus infection: results of a phase II study. J Infect Dis, : 1080-1086, 1997. 21 Nigro G, Adler SP, La Torre R, Best AM : Passive immunization during pregnancy for congenital cytomegalovirus infection. N Engl J Med, : 1350-1362, 2005. 22 Nigro G, La Torre R, Anceschi MM, Mazzocco M, Cosmi EV. Hyperimmunoglobulin therapy for a twin fetus with cytomegalovirus infection and growth restriction. Am J Obstet Gynecol ; : 1222-1226, 1999. 23 Snydman DR, Werner BG, Meissner HC, et al: Use of cytomegalovirus immunoglobulin in multiple transfused premature neonates. Pediatr Infect Dis J ; :34-40, 1995. 24 Numazaki K, Ikehata M, Yanai S, Umetsu M, Motoya H, Chiba S, Sekine T. Adoptive immunotherapy for interstitial pneumonia associated with cytomegalovirus infection. Clin Infect Dis, : 1246-1247, 1997. 25 Watts DH. Management of human immunodeficiency virus infection in pregnancy. N Engl J Med ; : 1879-1891, 2002. 26 Stagno S, Cloud GA : Working parents : the impact of day care and breast-feeding on cytomegalovirus infections in offspring. Proc Natl Acad Sci USA : 2384-2389, 1997. 27 Pass RF, et al: Vaccine Prevention of Maternal Cytomegalovirus Infection. N Engl J Med,, 1191-1199, 2009.