RESUMO
Investigation of sequence polymorphisms in the glycoprotein N (gN; gp4273), gO (gp4274) and gH (gp4275) genes of human cytomegalovirus (HCMV) strains collected from 63 Japanese children revealed that their gO genotype distribution differed slightly from that of Caucasian populations and that there was a significant linkage between the gN and gO genotypes. Linkage of these genotypes in strains obtained from Caucasian populations has been reported, so our similar findings in Japanese infants are consistent with this, and suggest generality of this linkage. Sequence analysis suggests that recombination between two strains of different linkage groups occurred approximately 200 bp upstream of the 3'-end of the gO gene. Further studies are required to elucidate differences in biological characteristics among the linkage groups and the selective constraints that maintain the linkage.
Assuntos
Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/virologia , Citomegalovirus/genética , Genes Virais , Glicoproteínas de Membrana/genética , Proteínas do Envelope Viral/genética , Citomegalovirus/classificação , Citomegalovirus/isolamento & purificação , Feminino , Ligação Genética , Humanos , Lactente , Recém-Nascido , Japão , Filogenia , Polimorfismo Genético , Gravidez , Recombinação GenéticaRESUMO
Guinea pig cytomegalovirus (GPCMV) provides a useful model for studies of congenital CMV infection. During characterization of the GPCMV genome sequence, we identified two types of strains in a virus stock purchased from ATCC. One of them, GPCMV/del, lacks a 1.6 kb locus that positionally corresponds to murine CMV (MCMV) M129-M133. Growth of GPCMV/del in cell culture was marginally better than that of the other strain, GPCMV/full, which harbors the 1.6 kb locus. However, in animals infected intraperitoneally with virus stocks containing both strains, GPCMV/full disseminated more efficiently than GPCMV/del, including 200-fold greater viral load in salivary glands. Viral DNA, transcripts of the immediate-early 2 gene homolog, and viral antigens were more abundant in animals infected with GPCMV/full than in those infected with GPCMV/del. Although the observed phenomena have some similarity with the growth properties of MCMV strains defective in mck-1/mck-2(M129/131) and those defective in sgg(M132), no M129-M132 homologs were found in the 1.6 kb locus. Since one of the ORFs in the locus has a weak sequence similarity with HCMV UL130, which relates to cell tropism, further studies will be required to learn the mechanism for efficient GPCMV growth in animal.
Assuntos
Roseolovirus/crescimento & desenvolvimento , Roseolovirus/patogenicidade , Deleção de Sequência , Replicação Viral , Animais , Antígenos Virais/biossíntese , Técnicas de Cultura de Células , Linhagem Celular , DNA Viral/biossíntese , DNA Viral/química , DNA Viral/genética , Genoma Viral , Cobaias , Fígado/patologia , Dados de Sequência Molecular , Filogenia , RNA Viral/biossíntese , Roseolovirus/genética , Infecções por Roseolovirus/virologia , Glândulas Salivares/virologia , Análise de Sequência de DNA , Homologia de Sequência , Baço/patologia , Ensaio de Placa ViralRESUMO
Human cytomegalovirus (CMV) is the leading cause of intrauterine viral infection. The association of genetic polymorphisms in some particular genes with the incidence and severity of congenital infection has been controversial. To address this issue, we analyzed the genotypes of the glycoprotein B (gB), UL144 and UL149 genes of CMV clinical strains obtained from 33 congenitally and 31 postnatally infected Japanese children. Our results demonstrated that (1) CMV strains with any combination of genotypes could be vertically transmitted from mother to fetus, potentially causing neurological abnormalities, (2) the gB3 genotype was more prevalent in the congenital cases than in postnatally infected children (P < 0.05), particularly in congenital cases with sensorineural hearing loss (P = 0.009), (3) there was no relationship between gB genotype and viral load in the urine and dried umbilical cord specimens in the congenital cases, and (4) the UL144 and UL149 genotype distributions had no bias for congenial infection. In future studies, it would be interesting to see whether the gB genotypes serve as a prognostic indicator of CMV-associated diseases.
Assuntos
Infecções por Citomegalovirus/congênito , Citomegalovirus/genética , Variação Genética , Transmissão Vertical de Doenças Infecciosas , Glicoproteínas de Membrana/genética , Proteínas do Envelope Viral/genética , Proteínas Virais/genética , Pré-Escolar , Citomegalovirus/classificação , Citomegalovirus/patogenicidade , Infecções por Citomegalovirus/fisiopatologia , Infecções por Citomegalovirus/virologia , Genótipo , Perda Auditiva Neurossensorial , Humanos , Incidência , Lactente , Recém-Nascido , Japão , Índice de Gravidade de DoençaRESUMO
Since congenital cytomegalovirus (CMV) infection causes late-onset sequelae, the identification of CMV-infected newborns is important. For this purpose, we established a simple real-time PCR assay using a filter disk. Combined with the collection of urine using filter papers placed in the diaper, this assay can make CMV screening more feasible and cost-effective.
