scholarly journals Congenital Human Cytomegalovirus Infection: A Narrative Review of Maternal Immune Response and Diagnosis in View of the Development of a Vaccine and Prevention of Primary and Non-Primary Infections in Pregnancy

2021 ◽  
Vol 9 (8) ◽  
pp. 1749
Author(s):  
Giuseppe Gerna ◽  
Chiara Fornara ◽  
Milena Furione ◽  
Daniele Lilleri
Keyword(s):  
Immune Response ◽  
Human Cytomegalovirus ◽  
Primary Infection ◽  
Cytomegalovirus Infection ◽  
Hcmv Infection ◽  
Antiviral Treatment ◽  
Virus Transmission ◽  
Immune Correlates ◽  
Maternal Immune Response ◽  
In Pregnancy

Congenital cytomegalovirus infection (cCMV) may affect about 1% of all newborns all over the world as a result of either a primary or recurrent human cytomegalovirus (HCMV) infection. While about 90% of infants affected by cCMV are asymptomatic at birth, the remaining 10% are symptomatic often with neurodevelopmental impairment and sensorineural hearing loss. In view of identifying the best approach to vaccine prevention of cCMV, this review will examine the most important steps made in the study of the immune response to, and diagnosis of, HCMV infection. The maternal immune response and immune correlates of protection are being partially identified with a partial contribution given by our laboratory. The diagnosis of primary infection is often difficult to achieve in the first three months of pregnancy, which is the time primarily involved in virus transmission to the fetus in association with the most severe symptoms and sequelae. Prevention of cCMV is anticipated by prevention of primary infection in early pregnancy by means of different measures, such as (i) behavioral-educational measures, (ii) immunoglobulin administration, (iii) antiviral treatment with valaciclovir. However, the most promising approach to cCMV prevention appears to be the development of a non-living vaccine, including at least three viral antigens: gB, pentamer complex gHgLpUL128L, and pp65, which have been shown to be able to stimulate both the humoral and the cellular arms of the maternal immune response. Primary HCMV infection may be managed in pregnancy by counseling of the couples involved by a team of specialists that includes virologists, obstetricians, infectivologists and neonatologists.

scholarly journals Immunobiology of Human Cytomegalovirus: from Bench to Bedside

2009 ◽  
Vol 22 (1) ◽  
pp. 76-98 ◽  
Author(s):  
Tania Crough ◽  
Rajiv Khanna
Keyword(s):  
Immune Response ◽  
Human Cytomegalovirus ◽  
Primary Infection ◽  
Hcmv Infection ◽  
Invasive Disease ◽  
Therapeutic Strategies ◽  
Viral Reactivation ◽  
Diagnostic Tools ◽  
Healthy Individuals ◽  
Immunological Effects

SUMMARY Following primary infection, human cytomegalovirus (HCMV) establishes lifelong latency and periodically reactivates without causing symptoms in healthy individuals. In the absence of an adequate host-derived immune response, this fine balance of permitting viral reactivation without causing pathogenesis is disrupted, and HCMV can subsequently cause invasive disease and an array of damaging indirect immunological effects. Over the last decade, our knowledge of the immune response to HCMV infection in healthy virus carriers and diseased individuals has allowed us to translate these findings to develop better diagnostic tools and therapeutic strategies. The application of these emerging technologies in the clinical setting is likely to provide opportunities for better management of patients with HCMV-associated diseases.

scholarly journals Pitfalls in the Serological Diagnosis of Primary Human Cytomegalovirus Infection in Pregnancy Due to Different Kinetics of IgM Clearance and IgG Avidity Index Maturation

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 396
Author(s):  
Antonella Sarasini ◽  
Alessia Arossa ◽  
Maurizio Zavattoni ◽  
Chiara Fornara ◽  
Daniele Lilleri ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Human Cytomegalovirus ◽  
Primary Infection ◽  
Hcmv Infection ◽  
Serological Diagnosis ◽  
Avidity Index ◽  
Igm Antibody ◽  
Igg Avidity ◽  
Kinetics Of ◽  
In Pregnancy

Primary infection occurs when seronegative women are infected by human cytomegalovirus (HCMV). Diagnosis of primary infection is based on the following: antibody seroconversion, presence of IgM and low IgG avidity index (AI), and presence of DNAemia. The kinetics of HCMV-specific IgM antibody and maturation of AI might be very rapid or long-lasting during primary infection, which makes serological diagnosis insidious. The aims of this study were as follows: (i) to report atypical kinetics of HCMV-specific IgM antibody and AI early after onset of primary HCMV infection in a population of pregnant women, and (ii) to assess the frequency of such results. Altogether, 1309 sequential serum samples collected from 465 pregnant women with primary HCMV infection were included in the study. As a general rule, using the LIAISON®CMVIgMII and LIAISON®CMVIgGAvidityII assays, virus-specific IgM antibody levels decreased, while IgG AI increased over time during the first three months after infection onset. However, early clearance of IgM antibody and/or early IgG AI maturation occurred in 46/426 (10.7%) women. In more details, 20/426 (4.7%) and 26/418 (6.2%) women had undetectable IgM antibody or high IgG AI, respectively, when tested within 1–3 months after well-defined infection onset. Twenty sera from as many women with high IgG AI by the LIAISON assay were further tested for IgG AI by VIDAS®CMVIgGAvidityII and Mikrogen recomLineCMVIgG Avidity assays. Comparable results were obtained with VIDAS, whereas 14/20 sera gave low AI with the Mikrogen assay. In conclusion, about 11% of pregnant women undergoing a primary HCMV infection showed misleading serological results. Additional and appropriate testing might help in reducing the risk of missing HCMV primary infection in pregnancy. Furthermore, preconceptional testing should be strongly recommended.

scholarly journals Human Cytomegalovirus Drives WDR5 to the Virion Assembly Compartment to Facilitate Virion Assembly

2020 ◽  
Author(s):  
Bo Yang ◽  
YongXuan Yao ◽  
Hui Wu ◽  
Hong Yang ◽  
Xue-Hui Ma ◽  
...  
Keyword(s):  
Human Cytomegalovirus ◽  
Hcmv Infection ◽  
Antiviral Treatment ◽  
Critical Role ◽  
Virion Assembly ◽  
Potential Target ◽  
Nuclear Egress ◽  
Early Endosomes ◽  
Hcmv Replication ◽  
Assembly Compartment

AbstractWe previously reported that human cytomegalovirus (HCMV) utilizes the cellular protein WDR5 to facilitate capsid nuclear egress. Here, we further show that HCMV infection drives WDR5 to the perinuclear region by a mechanism that requires viral replication and intact microtubules. WDR5 accumulated in the virion assembly compartment (vAC) and co-localized with vAC markers of gamma-tubulin (γ-tubulin), early endosomes, and viral vAC marker proteins pp65, pp28, and glycoprotein B (gB). WDR5 interacted with multiple virion proteins, including MCP, pp150, pp65, pIRS1, and pTRS1, which may explain the increasing WDR5 accumulation in the vAC during infection. WDR5 was then incorporated into HCMV virions and localized to the tegument layer, as demonstrated by fractionation and immune-gold electron microscopy. Thus, WDR5 is driven to the vAC and incorporated into virions, suggesting that WDR5 facilitates HCMV replication at later stage of virion assembly besides the capsid nuclear egress stage. These data highlight that WDR5 is a potential target for antiviral therapy.ImportanceHuman cytomegalovirus (HCMV) has a large (~235-kb) genome that contains over 170 ORFs and exploits numerous cellular factors to facilitate its replication. In the late phase of HCMV infection cytoplasmic membranes are profoundly reconfigured to establish the virion assembly compartment (vAC), which is important for efficient assembly of progeny virions. We previously reported that WDR5 promotes HCMV nuclear egress. Here, we show that WDR5 is further driven to the vAC and incorporated into virions, perhaps to facilitate efficient virion maturation. This work identified potential roles for WDR5 in HCMV replication in the cytoplasmic stages of virion assembly. Taken together, WDR5 plays a critical role in HCMV capsid nuclear egress and is important for virion assembly, and thus is a potential target for antiviral treatment of HCMV-associated diseases.

scholarly journals Primary Human Cytomegalovirus (HCMV) Infection in Pregnancy

2017 ◽  
Author(s):  
Horst Buxmann ◽  
Klaus Hamprecht ◽  
Matthias Meyer-Wittkopf ◽  
Klaus Friese
Keyword(s):  
Human Cytomegalovirus ◽  
Hcmv Infection ◽  
In Pregnancy

An effective and feasible approach to prevention of primary cytomegalovirus infection in pregnancy

2015 ◽  
Vol 36 (4) ◽  
pp. 179 ◽  
Author(s):  
Maria Grazia Revello ◽  
Valentina Frisina ◽  
Giovanna Oggè ◽  
Alessia Arossa ◽  
Milena Furione
Keyword(s):  
Primary Infection ◽  
Cytomegalovirus Infection ◽  
Seroconversion Rate ◽  
Controlled Study ◽  
Risk Of Infection ◽  
Behavioural Interventions ◽  
Primary Cytomegalovirus Infection ◽  
Protective Behaviours ◽  
In Pregnancy ◽  
Close Contacts

In the absence of a cytomegalovirus (CMV) vaccine, other strategies for prevention of primary infection in pregnancy should be considered. Behavioural interventions have been reported to significantly decrease seroconversion rate among seronegative pregnant women. We report here on a recently completed controlled study in which seronegative women at high risk of infection because of close contacts with children <36 months, were identified and informed about risky and protective behaviours. Informed women seroconverted at a significantly lower rate than non-informed women.

scholarly journals Diagnosis and Management of Human Cytomegalovirus Infection in the Mother, Fetus, and Newborn Infant

2002 ◽  
Vol 15 (4) ◽  
pp. 680-715 ◽  
Author(s):  
Maria Grazia Revello ◽  
Giuseppe Gerna
Keyword(s):  
Prenatal Diagnosis ◽  
Human Cytomegalovirus ◽  
Primary Infection ◽  
Hcmv Infection ◽  
Prognostic Markers ◽  
Recurrent Infection ◽  
Congenital Infection ◽  
Immunoglobulin M ◽  
Hcmv Disease ◽  
The Impact

SUMMARY Human cytomegalovirus (HCMV) is the leading cause of congenital viral infection and mental retardation. HCMV infection, while causing asymptomatic infections in most immunocompetent subjects, can be transmitted during pregnancy from the mother with primary (and also recurrent) infection to the fetus. Hence, careful diagnosis of primary infection is required in the pregnant woman based on the most sensitive serologic assays (immunoglobulin M [IgM] and IgG avidity assays) and conventional virologic and molecular procedures for virus detection in blood. Maternal prognostic markers of fetal infection are still under investigation. If primary infection is diagnosed in a timely manner, prenatal diagnosis can be offered, including the search for virus and virus components in fetal blood and amniotic fluid, with fetal prognostic markers of HCMV disease still to be defined. However, the final step for definite diagnosis of congenital HCMV infection is detection of virus in the blood or urine in the first 1 to 2 weeks of life. To date, treatment of congenital infection with antiviral drugs is only palliative both prior to and after birth, whereas the only efficacious preventive measure seems to be the development of a safe and immunogenic vaccine, including recombinant, subunit, DNA, and peptide-based vaccines now under investigation. The following controversial issues are discussed in the light of the most recent advances in the field: the actual perception of the problem; universal serologic screening before pregnancy; the impact of correct counseling on decision making by the couple involved; the role of prenatal diagnosis in ascertaining transmission of virus to the fetus; the impact of preconceptional and periconceptional infections on the prevalence of congenital infection; and the prevalence of congenitally infected babies born to mothers who were immune prior to pregnancy compared to the number born to mothers undergoing primary infection during pregnancy.

scholarly journals Development of Human Cytomegalovirus–Specific T Cell Immunity during Primary Infection of Pregnant Women and Its Correlation with Virus Transmission to the Fetus

2007 ◽  
Vol 195 (7) ◽  
pp. 1062-1070 ◽  
Author(s):  
Daniele Lilleri ◽  
Chiara Fornara ◽  
Milena Furione ◽  
Maurizio Zavattoni ◽  
Maria Grazia Revello ◽  
...  
Keyword(s):  
T Cell ◽  
Pregnant Women ◽  
Human Cytomegalovirus ◽  
Primary Infection ◽  
Virus Transmission ◽  
T Cell Immunity ◽  
Cell Immunity
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