Use of recombinant glycoprotein antigens gB and gH for diagnosis of primary human cytomegalovirus infection during pregnancy

Between the 1980s and 1990s, three assays were developed for diagnosis of human cytomegalovirus (HCMV) infections: leuko (L)-antigenemia, L-viremia and L-DNAemia, detecting viral protein pp65, infectious virus and viral DNA, respectively, in circulating leukocytes Repeated initial attempts to reproduce the three assays in vitro using laboratory-adapted strains and infected cell cultures were consistently unsuccessful. Results were totally reversed when wild-type HCMV strains were used to infect either fibroblasts or endothelial cells. Careful analysis and sequencing of plaque-purified viruses from recent clinical isolates drew attention to the ULb¢ region of the HCMV genome. Using bacterial artificial chromosome technology, it was shown by both gain-of-function and loss-of-function experiments that UL131-128 genes are indispensable for virus growth in endothelial cells and virus transfer to leukocytes. In addition, a number of clinical isolates passaged in human fibroblasts had lost both properties (leuko-tropism and endothelial cell-tropism) when displaying a mutation in the UL131-128 locus

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“…These results were attributed to a defect in IgG avidity maturation [72] and were confirmed by another group [73].…”

Section: Antibody Response To Pc and The Other Glycoprotein Complexessupporting

confidence: 58%

The pentameric complex of human Cytomegalovirus: cell tropism, virus dissemination, immune response and vaccine development

Gerna

Revello

Baldanti

et al. 2017

Journal of General Virology

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“…Epitope-specific IgG immunoblotting was investigated by Eggers et al (15) to explore the potentially different patterns in primary versus nonprimary infections. The authors compared an in-house-developed anti-gB/gH epitope immunoblot assay to a standard microneutralization method.…”

Section: Epitope-specific Igg Immunoblots To Assess Primary Versus Nomentioning

confidence: 99%

Testing for Cytomegalovirus in Pregnancy

et al. 2017

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Congenital cytomegalovirus (CMV) infection represents a relevant cause of deafness and neurological damage in newborns. Intrauterine CMV transmission might result after primary or nonprimary infections, though at different rates (30% versus 0.2%, respectively). At present, a prenatal diagnosis of CMV infection is based mainly on maternal serology, the detection of CMV-DNA in amniotic fluid and fetal blood, and ultrasound (US) and magnetic resonance imaging (MRI). Recent evidences suggest that congenital CMV infection may be an immune-mediated disease and that evaluation of humoral and especially T-cell immunities may improve the overall prenatal diagnosis. This review summarizes the most recent advancements in the diagnosis of maternal and prenatal CMV infections.KEYWORDS human cytomegalovirus, laboratory assays, congenital infections, IgG avidity, CMV-ELISPOT, CMV-QuantiFERON, immunoserology, imaging T he human cytomegalovirus (CMV) is a ubiquitous betaherpesvirus causing morbidity and mortality in immunocompromised patients and congenitally infected fetuses and newborns, resulting in a broad range of disabilities, including sensorineural hearing loss (SNHL), visual impairment, and motor and cognitive deficits. Other transient symptoms of congenital CMV infection (cCMV) may include hepatosplenomegaly, thrombocytopenia, and jaundice. The global prevalence of cCMV has been estimated at 0.7% (1), and fetal CMV transmission may arise from a maternal primary or nonprimary infection. The highest rate of cCMV occurs after primary infections in seronegative mothers (30 to 40%), while nonprimary infections, including CMV reactivations or reinfections, result in cCMV in 0.2 to 2% of cases, suggesting that preconceptional immunity may play a role in preventing intrauterine transmission (2). If the main burden of congenital infections in Europe and North America results from primary infections, then nonprimary infections represent the main cause of cCMV in developing countries or in poor socioeconomical contexts, since the seroprevalences among the resident populations are much higher (3). The severities of infections in neonates and infants are highly variable. It has been estimated that 10 to 15% of congenitally infected neonates are symptomatic at birth, and 40 to 58% of them will experience permanent long-term sequelae. Moreover, 13.5% of children with asymptomatic infections will develop late-onset sequelae, mainly consisting of hearing impairments and neurologic deficits. The effectiveness of antiviral treatment during pregnancy is still debated. Most of the concerns are related to the potential genotoxicity and teratogenicity of the drugs. The clinical benefits of CMV-specific hyperimmune globulin treatment are also disputed, due to discordant results obtained from different studies (4,5).In the last decade, major efforts have been made to improve the early laboratory diagnosis of maternal and fetal infections. Despite these efforts, at present, many countries in the world have not yet adopted a consolidate...

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“…The presence of maternal antibodies has been shown to be associated with a decreased incidence of CMV and with improved neurological outcomes in the setting of congenital infection (71,83). Paradoxically, immunoglobulin G (IgG) antibodies to the viral glycoprotein B (gB) after primary infection are significantly increased in maternal and newborn delivery sera for infants who develop hearing loss (33,38), suggesting a possible increased exposure to viral antigen.…”

Section: Introductionmentioning

confidence: 99%

Neuropathogenesis of Congenital Cytomegalovirus Infection: Disease Mechanisms and Prospects for Intervention

2009

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SUMMARY Congenital cytomegalovirus (CMV) infection is the leading infectious cause of mental retardation and hearing loss in the developed world. In recent years, there has been an improved understanding of the epidemiology, pathogenesis, and long-term disabilities associated with CMV infection. In this review, current concepts regarding the pathogenesis of neurological injury caused by CMV infections acquired by the developing fetus are summarized. The pathogenesis of CMV-induced disabilities is considered in the context of the epidemiology of CMV infection in pregnant women and newborn infants, and the clinical manifestations of brain injury are reviewed. The prospects for intervention, including antiviral therapies and vaccines, are summarized. Priorities for future research are suggested to improve the understanding of this common and disabling illness of infancy.

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Use of recombinant glycoprotein antigens gB and gH for diagnosis of primary human cytomegalovirus infection during pregnancy

Cited by 30 publications

References 41 publications

The pentameric complex of human Cytomegalovirus: cell tropism, virus dissemination, immune response and vaccine development

The pentameric complex of human Cytomegalovirus: cell tropism, virus dissemination, immune response and vaccine development

Testing for Cytomegalovirus in Pregnancy

Neuropathogenesis of Congenital Cytomegalovirus Infection: Disease Mechanisms and Prospects for Intervention

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