Congenital Cytomegalovirus Infection: Association between Virus Burden in Infancy and Hearing Loss

Boppana, Suresh B.; Fowler, Karen B.; Pass, Robert F.; Rivera, Lisa B.; Bradford, Russell D.; Lakeman, Fred D.; Britt, William J.

doi:10.1016/j.jpeds.2005.01.059

Cited by 246 publications

(192 citation statements)

References 34 publications

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“…DNA was extracted from urine and peripheral blood specimens with a commercial spin column kit (Qiagen Inc., Chatsworth, CA). The samples were initially tested for the presence of CMV DNA by PCR with primers from the antigen domain 1 region of the gene encoding glycoprotein B as described previously (4). The antigen domain 1 region of gB has been shown to be highly conserved among clinic isolates of CMV (9).…”

Section: Methodsmentioning

confidence: 99%

Cytomegalovirus Strain Diversity in Seropositive Women

et al. 2008

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Infection and reinfection with multiple cytomegalovirus (CMV) strains have been shown to occur in immunocompromised individuals, sexually transmitted disease clinic attendees, and children attending day care centers. To characterize the CMV diversity in healthy seropositive individuals, 16 CMV PCR-positive specimens from 113 seropositive women were analyzed for glycoprotein gN and gB genotypes by cloning, followed by nucleotide sequencing of the plasmid DNA and/or restriction fragment length polymorphism (RFLP). The results showed that most (93.7%) of the PCR-positive specimens contained multiple gN and/or gB genomic variants, suggesting that the majority of women were infected with more than one virus strain. The results also showed that the RFLP technique might not be sufficiently sensitive to detect all of the genomic variants present in a sample.Cytomegalovirus (CMV) species are important opportunistic agents in infection of immunocompromised individuals and a frequent cause of congenital infection. Infection with multiple strains of CMV has been shown to occur frequently in immunocompromised individuals and sexually transmitted disease (STD) clinic attendees (8, 10). In addition, reinfection with different CMV strains was documented to occur in children attending day care centers (2). More recently, CMV reinfections were demonstrated in seropositive women, and such reinfections can result in intrauterine transmission and damaging fetal infection (5).Extensive genetic polymorphisms in envelope glycoproteins of CMV, including glycoprotein B (gpUL55), glycoprotein O (gpUL74), and glycoprotein N (gpUL73), have been demonstrated among clinical CMV isolates. Major envelope glycoprotein B (gB) of CMV has been demonstrated to elicit a strong neutralizing antibody response (6), and on the basis of restriction fragment length polymorphism (RFLP) analysis of clinical samples, four unique genomic variants, gB types 1 to 4, have been identified (9). Glycoprotein N has been shown to be highly polymorphic at the amino-terminal region, and most clinical CMV isolates have been shown to cluster into four distinct genomic variants, gN-1, gN-2, gN-3a, gN-3b, gN-4a, gN-4b, and gN-4c (11). Recent studies have shown that a significant proportion of the virus-neutralizing response was also directed against the gM/gN complex (17). No linkage between gN genotypes and gB genotypes has been observed (11).Published studies using RFLP analyses to determine the gN genotypes have identified only a single gN type in a given sample (11, 13). Studies of glycoprotein B based on RFLP analyses showed the presence of a single genotype or a limited number of samples containing mixtures of two gB genotypes (3, 7). However, a recent study using hybridization with typespecific probes (10) showed mixtures of all genotypes. To determine the CMV strain diversity in healthy seropositive women, the presence of multiple gN and gB genomic variants in urine or peripheral blood was examined by two different methods, RFLP and cloning followed by nucleotide se...

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Section: Methodsmentioning

confidence: 99%

Cytomegalovirus Strain Diversity in Seropositive Women

et al. 2008

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“…Human cytomegalovirus (HCMV) is the leading viral cause of congenital birth defects, including mental retardation and blindness, and the leading nongenetic cause of neurosensory hearing loss in developed countries (8,29). In addition to its impact on neonatal health, HCMV is a significant pathogen in immunosuppressed adults, particularly in transplant recipients (7,29).…”

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Mitochondrial and Secretory Human Cytomegalovirus UL37 Proteins Traffic into Mitochondrion-Associated Membranes of Human Cells

Bozidis

Williamson

Colberg-Poley

2008

J Virol

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The human cytomegalovirus (HCMV) UL37 exon 1 protein (pUL37x1), also known as vMIA, is the predominant UL37 isoform during permissive infection. pUL37x1 is a potent antiapoptotic protein, which prevents cytochrome c release from mitochondria. The UL37x1 NH 2 -terminal bipartite localization signal, which remains uncleaved, targets UL37 proteins to the endoplasmic reticulum (ER) and then to mitochondria. Based upon our findings, we hypothesized that pUL37x1 traffics from the ER to mitochondria through direct contacts between the two organelles, provided by mitochondrion-associated membranes (MAMs). To facilitate its identification, we cloned and tagged the human phosphatidylserine synthase 1 (huPSS-1) cDNA, whose mouse homologue localizes almost exclusively in the MAM. Using subcellular fractionation of stable HeLa cell transfectants expressing mEGFP-huPSS-1, we found that HCMV pUL37x1 is present in purified microsomes, mitochondria, and MAM fractions. We further examined the trafficking of the full-length UL37 glycoprotein cleavage products, which divergently traffic either through the secretory apparatus or into mitochondria. Surprisingly, pUL37 NH2 and gpUL37 COOH were both detected in the ER and MAM fraction, even though only pUL37 NH2 is preferentially imported into mitochondria but gpUL37 COOH is not. To determine the sequences required for MAM importation, we examined pUL37x1 mutants that were partially defective for mitochondrial importation. Deletion mutants of the NH 2 -terminal UL37x1 mitochondrial localization signal were reduced in trafficking into the MAM, indicating partial overlap of MAM and mitochondrial targeting signals. Taken together, these results suggest that HCMV UL37 proteins traffic from the ER into the MAM, where they are sorted into either the secretory pathway or to mitochondrial importation.

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“…Значимость абсолютного уровня репликации ци-томегаловируса, полученного с помощью количе-ственного метода ПЦР, до конца не выяснена. В ряде исследований показана связь вирусной нагрузки в крови/моче с развитием симптоматического ва-рианта врожденной цитомегаловирусной инфекции и последующей тугоухости [36][37][38]. Украинские ав-торы (2013) продемонстрировали корреляцию вы-сокой вирусной нагрузки (более 5·10 3 копий в 1 мл мочи, полученной в родильном зале) с повышением риска нарушений нервно-психического развития и слуха к возрасту 1 года [39].…”

Section: клиническая картина и диагностика врожденной цитомегаловирусunclassified