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1.
PLoS Pathog ; 13(6): e1006377, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28575072

ABSTRACT

Viral infections during pregnancy are a significant cause of infant morbidity and mortality. Of these, rubella virus infection is a well-substantiated example that leads to miscarriages or severe fetal defects. However, structural information about the rubella virus has been lacking due to the pleomorphic nature of the virions. Here we report a helical structure of rubella virions using cryo-electron tomography. Sub-tomogram averaging of the surface spikes established the relative positions of the viral glycoproteins, which differed from the earlier icosahedral models of the virus. Tomographic analyses of in vitro assembled nucleocapsids and virions provide a template for viral assembly. Comparisons of immature and mature virions show large rearrangements in the glycoproteins that may be essential for forming the infectious virions. These results present the first known example of a helical membrane-enveloped virus, while also providing a structural basis for its assembly and maturation pathway.


Subject(s)
Rubella virus/physiology , Rubella/virology , Virus Assembly , Animals , Cell Line , Electron Microscope Tomography , Humans , Nucleocapsid/genetics , Nucleocapsid/metabolism , Rubella/embryology , Rubella/pathology , Rubella virus/chemistry , Rubella virus/genetics , Rubella virus/ultrastructure , Teratogenesis
2.
Am J Reprod Immunol ; 73(3): 199-213, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25582523

ABSTRACT

Viral infections during pregnancy have long been considered benign conditions with a few notable exceptions, such as herpes virus. The recent Ebola outbreak and other viral epidemics and pandemics show how pregnant women suffer worse outcomes (such as preterm labor and adverse fetal outcomes) than the general population and non-pregnant women. New knowledge about the ways the maternal-fetal interface and placenta interact with the maternal immune system may explain these findings. Once thought to be 'immunosuppressed', the pregnant woman actually undergoes an immunological transformation, where the immune system is necessary to promote and support the pregnancy and growing fetus. When this protection is breached, as in a viral infection, this security is weakened and infection with other microorganisms can then propagate and lead to outcomes, such as preterm labor. In this manuscript, we review the major viral infections relevant to pregnancy and offer potential mechanisms for the associated adverse pregnancy outcomes.


Subject(s)
Pregnancy Complications, Infectious/immunology , Virus Diseases/immunology , Animals , Coinfection , Congenital Abnormalities/etiology , Female , Fetal Diseases/immunology , HIV Infections/congenital , HIV Infections/embryology , HIV Infections/immunology , HIV Infections/transmission , Hepatitis, Viral, Human/embryology , Hepatitis, Viral, Human/immunology , Hepatitis, Viral, Human/transmission , Herpesviridae Infections/embryology , Herpesviridae Infections/immunology , Herpesviridae Infections/transmission , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Influenza, Human/embryology , Influenza, Human/immunology , Maternal-Fetal Exchange/immunology , Obstetric Labor, Premature/etiology , Placenta/immunology , Placenta/virology , Pregnancy , Pregnancy Complications, Infectious/virology , Pregnancy Outcome , Risk , Rubella/embryology , Rubella/immunology , Rubella/transmission , Virus Diseases/transmission
3.
J Gynecol Obstet Biol Reprod (Paris) ; 40(2): 109-15, 2011 Apr.
Article in French | MEDLINE | ID: mdl-21345623

ABSTRACT

Intra-uterine growth retardation (IUGR) is a frequent cause of consultation in antenatal care unit. The prognosis relies on the etiology: vascular, chromosomic, genetic, or infectious. Because of chronic fetal distress, hypotrophy increase morbidity, mortality and neurosensorial long term effect. Usually, infection is involved in 5 to 15% of the IUGR, mainly by Cytomegalovirus (CMV), Varicella Zoster virus, rubella, toxoplasmosis, herpes and syphilis. Maternal sera and amniotic liquid analysis make the diagnosis possible but fetal ultrasound scan is used to find other features. Most of the abnormalities are unspecific but their combination can worsen fetal prognosis. Infection should always be ruled out in the assessment of IUGR.


Subject(s)
Fetal Growth Retardation/etiology , Infections , Chickenpox/complications , Chickenpox/diagnostic imaging , Chickenpox/embryology , Cytomegalovirus Infections/complications , Cytomegalovirus Infections/diagnostic imaging , Cytomegalovirus Infections/embryology , Female , Fetal Diseases/microbiology , Fetal Growth Retardation/diagnostic imaging , Fetal Growth Retardation/microbiology , Herpesviridae Infections/complications , Herpesviridae Infections/diagnostic imaging , Herpesviridae Infections/embryology , Humans , Pregnancy , Prognosis , Rubella/complications , Rubella/diagnostic imaging , Rubella/embryology , Syphilis/complications , Syphilis/diagnostic imaging , Syphilis/embryology , Toxoplasmosis/complications , Toxoplasmosis/diagnostic imaging , Toxoplasmosis/embryology , Ultrasonography, Prenatal
4.
Curr Opin Obstet Gynecol ; 16(2): 163-6, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15017347

ABSTRACT

PURPOSE OF REVIEW: The purpose of this review is to present recent developments in the prenatal diagnosis of the most clinically relevant congenital infections. RECENT FINDINGS: Immunoglobin G avidity testing can help to differentiate between recent or prior infection. A combination of tests, including serology, avidity and polymerase chain reaction, may be necessary to improve accuracy of diagnosis. The interval between exposure to an infectious agent and prenatal testing can be critical to the interpretation of the test result. SUMMARY: This review reinforces the need for accurate testing to guide appropriate counseling and individual fetal risk assessment. The findings of viral-specific antibodies or sonographic abnormalities do not accurately predict the severity or outcome of fetal infection. Further research is necessary to determine the pathogenesis of transplacental viral transmission and thereby allow us to target prevention strategies.


Subject(s)
Fetal Diseases/diagnosis , Fetus/physiopathology , Infections/diagnosis , Prenatal Diagnosis/methods , Antibody Affinity , Chickenpox/congenital , Chickenpox/diagnosis , Chickenpox/embryology , Cytomegalovirus Infections/congenital , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/embryology , Female , Fetal Blood/chemistry , Fetal Diseases/parasitology , Fetal Diseases/virology , Humans , Immunoglobulin G/analysis , Infections/congenital , Infections/embryology , Infections/transmission , Infectious Disease Transmission, Vertical , Parvovirus/isolation & purification , Pregnancy , Rubella/congenital , Rubella/diagnosis , Rubella/embryology , Serologic Tests , Toxoplasmosis/diagnosis , Toxoplasmosis/embryology
5.
Am J Obstet Gynecol ; 174(2): 578-82, 1996 Feb.
Article in English | MEDLINE | ID: mdl-8623788

ABSTRACT

OBJECTIVE: Our purpose was to develop a reliable method for prenatal diagnosis of fetal rubella infection through the detection of viral ribonucleic acid extracted from the chorionic villi, amniotic fluid, or fetal blood in pregnant women. STUDY DESIGN: Double amplification of rubella viral ribonucleic acid by nested polymerase chain reaction after reverse transcription was applied to samples from 34 women suspected of having rubella. The results were compared with those of serum antibody and levels of rubella virus-specific immunoglobulin M antibodies in fetal blood. RESULTS: Viral ribonucleic acid was revealed in 8 of 34 cases (23.5%). In the remaining 26 cases, healthy babies were born in 24, 1 was electively aborted, and 1 died in the thirty-sixth week of pregnancy of unknown causes. CONCLUSIONS: This method allowed very early detection of fetal rubella infection by sampling of chorionic villi and amniotic fluid compared with evaluation of the maternal symptoms and serum antibody levels. Fetal blood was also more useful for making a diagnosis up to the twentieth week of pregnancy than was measuring rubella virus-specific immunoglobulin M antibodies.


Subject(s)
Fetal Diseases/diagnosis , Polymerase Chain Reaction , Prenatal Diagnosis , RNA, Viral/blood , Rubella virus/genetics , Rubella/diagnosis , Adult , Antibodies, Viral/blood , Female , Fetal Blood/virology , Humans , Immunoglobulin M/blood , Pregnancy , Pregnancy Outcome , RNA-Directed DNA Polymerase , Rubella/embryology , Rubella virus/immunology
6.
Blood ; 84(6): 1851-6, 1994 Sep 15.
Article in English | MEDLINE | ID: mdl-8080991

ABSTRACT

Fetal platelet counts were retrospectively studied in a series of 5,194 consecutive fetal blood samplings (FBS). The mean value was 245 +/- 65 x 10(9)/L, without significant variation between 17 and 41 weeks' gestation. After exclusion of false thrombocytopenia due to contamination with amniotic fluid, 247 fetuses had platelet counts less than 150 x 10(9)/L. In 70 cases, thrombocytopenia was due to congenital infectious diseases (toxoplasmosis, rubella, and cytomegalovirus). It was related to immune causes in 45 cases: anti-HPA-1a (n = 23), anti-HPA-5b (n = 2) or possible anti-HLA (n = 2) alloimmunizations, and immune thrombocytopenic purpura (n = 18). Chromosomal abnormality was the etiology in 43 cases (trisomy 13, 18, and 21, Turner's syndrome, triploidy), and other disorders (multiple birth defects, intrauterine growth retardation, rhesus disease, and gestational thrombocytopenia) in 62 cases. No specific cause for the low platelet count could be established in 27 fetuses (range, 115 to 149 x 10(9)/L). Severe thrombocytopenia (< or = 50 x 10(9)/L) occurred mainly in immune cases (16%), congenital infectious diseases (7%), and chromosomal abnormalities (1%). Diagnosis, prognosis, and management of fetal thrombocytopenia are presented in the different clinical situations. In this series, FBS was never associated with serious bleeding, and no fetal exsanguination was observed.


Subject(s)
Fetal Diseases/blood , Thrombocytopenia/embryology , Chromosome Aberrations , Cytomegalovirus Infections/complications , Cytomegalovirus Infections/embryology , Gestational Age , Humans , Immunization , Isoantibodies , Platelet Count , Retrospective Studies , Rubella/complications , Rubella/embryology , Thrombocytopenia/blood , Thrombocytopenia/etiology , Toxoplasmosis/complications , Toxoplasmosis/embryology , Trisomy , Turner Syndrome/blood
8.
J Gen Virol ; 71 ( Pt 7): 1607-11, 1990 Jul.
Article in English | MEDLINE | ID: mdl-2374011

ABSTRACT

We have used the polymerase chain reaction (PCR) to provide a very sensitive and unequivocal test for diagnosis of foetal rubella virus infection. RNA extracted from biopsy specimens (chorionic villi), placenta or products of conception was reverse-transcribed using a rubella virus-specific oligonucleotide primer and the cDNA was amplified by PCR. The specificity of the amplified fragment was confirmed by Southern blotting. Detection of rubella virus infection in five out of 41 clinical specimens examined by this approach was shown to be entirely consistent with clinical history and other methods of laboratory diagnosis in current use. The sensitivity of the test and the unequivocal nature of the results obtained could be invaluable in providing prenatal counselling following rubella virus infection during pregnancy.


Subject(s)
RNA, Viral/isolation & purification , Rubella virus/genetics , Rubella/diagnosis , Animals , Base Sequence , Chorionic Villi/microbiology , Female , Humans , Molecular Sequence Data , Oligonucleotide Probes , Polymerase Chain Reaction/methods , Pregnancy , Prenatal Diagnosis , RNA, Viral/genetics , Rubella/embryology , Rubella virus/isolation & purification , Vero Cells
10.
Lancet ; 1(8055): 57-60, 1978 Jan 14.
Article in English | MEDLINE | ID: mdl-74564

ABSTRACT

The incidence of diabetes mellitus was increased in patients with congenital rubella. Experimental congenital rubella infection in rabbits caused histological changes in the beta-cells of the pancreatic islets similar to those found in mice made diabetic by the M variant of the encephalomyocarditis virus. It is concluded that the diabetes seen in congenital rubella is due to viral infection of the pancreatic islet cells.


Subject(s)
Diabetes Mellitus/etiology , Rubella/complications , Adult , Animals , Child , Cytoplasm/ultrastructure , Diabetes Mellitus, Type 1/etiology , Female , Fetus/pathology , Follow-Up Studies , Humans , Infant , Islets of Langerhans/pathology , Male , Microscopy, Electron , Pregnancy , Rabbits , Rubella/congenital , Rubella/embryology
11.
Morphol Embryol (Bucur) ; 22(1): 41-5, 1976.
Article in English | MEDLINE | ID: mdl-130547

ABSTRACT

Rabbits were used as experimental subjects for study of circulation of the rubella virus in intrauterine life and of the histopathological alterations produced by inoculation of wild strains during the first third of pregnancy. Fetuses taken in the 14th, 21st and 28th days of pregnancy, as well as 1-month-old and 5-month-old animals were used for the embryologic and virological studied. Of the 20 animals infected, 90% presented histopathological lesions. The most affected viscera being the liver (80%), heart (60%). kidney (30%) and the crystalline lens (5%). Virological study was made of only 11 animals, from which 100% viral isolation was obtained, with similar results between viral isolation and the appearance of lesions in the liver (72%) and the kidney (44%), while a marked discrepancy in the virus-lesion relationship was found for the heart (33%) and the crystalline lens (77%). We conclude that the etiopathogeny of the syndrome cannot be explained only by direct action of the virus on the fetal tissues, but must be multiple.


Subject(s)
Liver/pathology , Myocardium/pathology , Pregnancy Complications, Infectious/pathology , Rubella virus , Rubella/pathology , Animals , Cell Differentiation , Disease Models, Animal , Embryo, Mammalian , Female , Histocytochemistry , Liver/embryology , Maternal-Fetal Exchange , Megakaryocytes/pathology , Pregnancy , Rabbits , Rubella/embryology , Rubella Vaccine/administration & dosage
12.
J Exp Med ; 141(6): 1238-48, 1975 Jun 01.
Article in English | MEDLINE | ID: mdl-1092795

ABSTRACT

The clinically known sensitive period of rubella cataract was studied in vitro by infecting 79 human eye rudiments from embryos aged 4-10 wk with rubella virus. The course of the infection was followed by histological and indirect immunofluorescence methods. Of the rudiments, 12 pairs were in the lens placode or open-lens-vesicle stage, 40 already had closed lens vesicles and in another 27 closed-stage pairs an incision was made in the lens capsule before infection to allow the virus to enter the lens. Uninfected controls differentiated well in vitro for 4-6 wk. The eye rudiments infected in the open-lens-vesicle stage showed lens fiber destruction and viral antigens within the lens. No damage or viral antigens were detected in rudiments infected in the closed stage unless the lens capsule was incisedmwhen this was done, however, fiber damage ensued and viral antigens appeared. The lens capsule was concluded to form a protective barrier around the sensirive fibers at the time of closure of the lens vesicle, confirming the earlier hypothesis and clinical findings.


Subject(s)
Cataract/embryology , Lens, Crystalline/embryology , Rubella/embryology , Antigens, Viral/analysis , Cataract/etiology , Embryo, Mammalian , Eye/embryology , Fluorescent Antibody Technique , Humans , Microscopy, Fluorescence , Organ Culture Techniques , Rubella/complications , Rubella virus/immunology
20.
N Engl J Med ; 274(14): 768-71, 1966 Apr 07.
Article in English | MEDLINE | ID: mdl-17926883

ABSTRACT

Comparative data on fetal and neonatal deaths following maternal mumps, rubella, hepatitis, chicken pox and measles were obtained in a prospective study in New York City from 1957 to 1964, inclusive. The evidence pointed to an increase in early fetal death rate after rubella and mumps and an increase in perinatal mortality after rubella and hepatitis. A significant increase in these rates was not demonstrable for chicken pox and measles in the selected population studied and under the conditions of the present study. The lethal effects of maternal virus diseases were demonstrable in cases of mumps and rubella occurring in the early weeks of gestation and in cases of hepatitis occurring in the late weeks of pregnancy. Fetal death was attributable to severity of maternal disease in hepatitis and to early infection of the fetus in rubella. Other factors related to gonadal infection and to placental and hormonal changes early in pregnancy may be influential in the lethal effect of mumps. Maternal and fetal death occurred in single cases of chicken-pox pneumonia and hepatitis.


Subject(s)
Chickenpox , Fetal Death/etiology , Fetal Mortality , Hepatitis, Viral, Human , Pregnancy Complications, Infectious , RNA Virus Infections , Case-Control Studies , Chickenpox/epidemiology , Chickenpox/mortality , Female , Hepatitis, Viral, Human/epidemiology , Hepatitis, Viral, Human/mortality , Humans , Maternal Mortality , Measles , Mumps , New York City/epidemiology , Pregnancy , Pregnancy Complications, Infectious/mortality , Prospective Studies , RNA Virus Infections/epidemiology , Rubella/embryology
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