Abnormal Development - Cytomegalovirus

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P35.1 Congenital cytomegalovirus infection

International Classification of Diseases: P35 Congenital viral diseases | XVI Perinatal Period
Viral Links: viral infection | TORCH | cytomegalovirus | hepatitis | HIV | parvovirus | polio | rubella virus | chickenpox | Lymphocytic Choriomeningitis Virus | Zika virus | human papillomavirus | rotavirus | West Nile virus | varicella virus | vaccination | zoonotic infection | environment
Historic Embryology - Viral 
1941 Rubella Cataracts | 1944 Rubella Defects

Introduction

Cytomegalovirus infected spermatozoon[1]

Human cytomegalovirus (HCMV, Greek, cyto = "cell", megalo = "large") or Human Herpesvirus 5 (HHV-5) is a member of the herpes virus family. A viral infection that causes systemic infection and extensive brain damage and cell death by necrosis. Cytomegalovirus is the leading cause of congenital viral infection, with a range of incidence between 0·5–3% of live births worldwide. Approximately 30% of maternal infections during pregnancy can result in congenital infection. Neonates with congenital or perinatal cytomegalovirus infection can be asymptomatic and infection can also be transmitted postnatally from mother to infant by breastfeeding.

HCMV infection is ranked as one of the most common infections in adults, with the seropositive rates ranging from 60–99% globally. In Western countries, adults with advanced AIDS prior to the introduction of highly active antiretroviral therapy (HAART) this virus also a cause of blindness (CMV retinitis) and death in patients.

Congenital cytomegalovirus infection is also a cause of non-hereditary congenital sensorineural hearing loss.[2]

CDC Congenital abnormality graph.jpg

Some Recent Findings

Human cytomegalovirus beta-catenin juxtanuclear region[3]
  • Human fetal inner ear involvement in congenital cytomegalovirus infection[4] "Congenital cytomegalovirus (CMV) infection is a leading cause of sensorineural hearing loss (SNHL). ...CMV-infection of the marginal cell layer of the stria vascularis may alter potassium and ion circulation, dissipating the endocochlear potential with consequent SNHL. Although abnormal cerebral ultrasound is highly predictive of brain and inner ear damage, normal ultrasound findings cannot exclude them either." Hearing Abnormalities
  • Human Cytomegalovirus Infection Dysregulates the Canonical Wnt/β-catenin Signaling Pathway[3] "In this study, we demonstrate that HCMV dysregulates Wnt/β-catenin signaling in dermal fibroblasts and human placental extravillous trophoblasts. Infection inhibits Wnt-induced transcriptional activity of β-catenin and expression of β-catenin target genes in these cells. HCMV infection leads to β-catenin protein accumulation in a discrete juxtanuclear region. Levels of β-catenin in membrane-associated and cytosolic pools, as well as nuclear β-catenin, are reduced after infection; while transcription of the β-catenin gene is unchanged, suggesting enhanced degradation. Given the critical role of Wnt/β-catenin signaling in cellular processes, these findings represent a novel and important mechanism whereby HCMV disrupts normal cellular function."
  • A preliminary evaluation of safety and efficacy of standard intravenous immunoglobulins in pregnant women with primary Cytomegalovirus infection[5] "Hyperimmune globulins were reported to prevent and treat fetal CMV infection during pregnancy. Here we report that infusions of standard human intravenous immunoglobulin significantly increase CMV IgG titres and avidity indexes in pregnant women, paving the way to their use for passive transfer of maternal CMV humoral immunity to foetuses. Preliminary data on perinatal outcomes of the first 67 newborns are encouraging." ClinicalTrials.gov NCT01659684
  • Update on the prevention, diagnosis and management of cytomegalovirus infection during pregnancy[6] "Given the high risk of mother-fetus transmission and fetal damage, prenatal diagnosis is recommended to women with primary CMV infection contracted in the first half of pregnancy and in case of fetal abnormalities suggestive of infection. The correct interpretation of serological and virological tests followed by appropriate counselling by an expert physician is an effective tool to reduce the number of unnecessary pregnancy terminations by over 70% (Am J Obstet Gynecol 2007; 196: 221.e1)."

Cytomegalovirus Structure

  • double-stranded linear DNA virus
  • 235 Kb in size

Cytomegalovirus infected spermatozoa nucleus[1]

Cytomegalovirus infected spermatozoa EM01.jpg Cytomegalovirus virions EM.jpg
Full and empty viral capsids HCMV virions


Links: Genome | Sequence

Cytomegalovirus Detection

Cytomegalovirus Detection

Image shows human embryonic lung infected by cytomegalovirus demonstrated by an immunofluorescent technique. Viral infection causes systemic infection and extensive brain damage and cell death by necrosis.

A combination of tests has been used for prenatal diagnosis and there are some less reliable sonographic features to the infection.

  • maternal serum - specific immunoglobulin (IgM) antibodies
  • amniotic fluid - viral culture and PCR amplification of CMV DNA.

Cytomegalovirus History

  • 1921 - first to suggest that the "cytomegalia" could be due to a viral agent.
  • 1950 - demonstrated that infection may occur in utero.
  • 1956-57 - several groups independently isolate human CMV strains.
  • 1960 - the term "cytomegalovirus" introduced.


Cytomegalovirus Musculoskeletal

A mouse model of effects of cytomegalovirus infection on development has shown induction of micrognathia and other musculoskeletal abnormalities by impacting on signalling pathways, involving FN, NF-kappaB2, RelA, RelB, and Shh and Smad7 proteins. Cytomegalovirus induced micrognathia and abnormal skeletogenesis.jpg

Cytomegalovirus induced micrognathia and abnormal skeletogenesis in mouse model.[7]

Cytomegalovirus Placentitis

Clinical term for the cytomegalovirus infection of the placenta.

A earlier histological study[8] identified fixed connective tissue cells predominantly infected cell type in placental tissue. In addition, endothelial cells, macrophages and in some cases trophoblast infection. While a more recent in vitro study[9] suggests that all villi cell types are likely to be infected.

References

  1. 1.0 1.1 <pubmed>21711549</pubmed>| Herpesviridae.
  2. <pubmed>22033878</pubmed>
  3. 3.0 3.1 <pubmed>23071438</pubmed>| PLoS Pathog.
  4. <pubmed>24252374</pubmed>
  5. <pubmed>23100477</pubmed>
  6. <pubmed>21631642</pubmed>
  7. <pubmed>18371224</pubmed>| BMC Dev Biol.
  8. <pubmed>8236822</pubmed>
  9. <pubmed>21392403</pubmed>

Textbooks

Reviews

<pubmed></pubmed> <pubmed></pubmed> <pubmed>21364849</pubmed> <pubmed>21375790</pubmed> <pubmed>18073181</pubmed> <pubmed>17635529</pubmed> <pubmed>16635273</pubmed> <pubmed>12364375</pubmed>

Articles

<pubmed></pubmed> <pubmed></pubmed> <pubmed></pubmed> <pubmed>21072294</pubmed> <pubmed>20388893</pubmed> <pubmed>9042169</pubmed>

Search Pubmed

Search Pubmed: Cytomegalovirus Virus | Congenital Cytomegalovirus Syndrome | Congenital Cytomegalovirus Infection | cytomegalovirus placentitis


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Cite this page: Hill, M.A. (2020, April 8) Embryology Abnormal Development - Cytomegalovirus. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Abnormal_Development_-_Cytomegalovirus

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© Dr Mark Hill 2020, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G