Molecular Biology of Rubella Virus

Frey, Teryl K.

doi:10.1016/s0065-3527(08)60328-0

Cited by 250 publications

(259 citation statements)

References 345 publications

(241 reference statements)

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“…The RV capsid protein, excluding the E2 signal peptide, is a 277-amino-acid residue protein that forms disulfide-linked dimers (6,17). The C-terminal part of the protein (amino acids 127-277) was expressed and purified from bacteria (Materials and Methods).…”

Section: Resultsmentioning

confidence: 99%

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Rubella virus capsid protein structure and its role in virus assembly and infection

Prasad

Willows

Fokine

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Rubella virus (RV) is a leading cause of birth defects due to infectious agents. When contracted during pregnancy, RV infection leads to severe damage in fetuses. Despite its medical importance, compared with the related alphaviruses, very little is known about the structure of RV. The RV capsid protein is an essential structural component of virions as well as a key factor in virus-host interactions. Here we describe three crystal structures of the structural domain of the RV capsid protein. The polypeptide fold of the RV capsid protomer has not been observed previously. Combining the atomic structure of the RV capsid protein with the cryoelectron tomograms of RV particles established a low-resolution structure of the virion. Mutational studies based on this structure confirmed the role of amino acid residues in the capsid that function in the assembly of infectious virions.X-ray crystallography | cryoelectron tomography | virology R ubella virus (RV) is the only member of the Rubivirus genus which, together with alphaviruses including Chikungunya virus, Sindbis virus, and Ross River virus, make up the family Togaviridae. RV is a human pathogen that causes "German measles," a relatively mild disease characterized by rashes and low-grade fever. However, due to its teratogenic properties, RV is a major threat to the fetus when infection occurs during the first trimester of pregnancy (1). Vaccination has been very successful in controlling RV infection; however, the virus is still endemic in many areas of the world (1, 2). RV is an enveloped virus with a 9.6-kb single-stranded, positive-sense RNA genome (1, 3). The virions have particle diameters ranging from 600 to 800 Å, with most of the spherical virions having a diameter of about 700 Å (4). RV contains three structural proteins, namely, the capsid protein (∼31 kDa) and the glycoproteins E1 (58 kDa) and E2 (42-47 kDa). The capsid protein interacts with the RNA genome and forms the nucleocapsid, which is surrounded by a lipid membrane upon which E1 and E2 are arranged. Two nonstructural proteins, p90 and p150, involved with virus replication, are also encoded by the virus (1).Alphaviruses and RV share a similar gene order and expression strategy (3) but differ from each other in that alphaviruses are icosahedral, their nucleocapsids assemble in the cytoplasm, and virions bud from the plasma membrane (5). In contrast, RV virions are pleomorphic and the nucleocapsid assembles on Golgi membranes followed by budding of the virus into this organelle (6). The pleomorphic nature of RV virions has been a limiting factor in determining the structure of the virus particles.As with all Togaviruses, the structural proteins of RV are synthesized as a polyprotein precursor in association with the endoplasmic reticulum in the host cell (7) (Fig. 1A). The polyprotein is cotranslationally cleaved by the host-cell signal peptidase but, unlike alphavirus capsid proteins, the RV capsid protein remains attached to the cytoplasmic side of the membrane by virtue of the hydrophobic E2 ...

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Section: Resultsmentioning

confidence: 99%

“…In contrast, RV virions are pleomorphic and the nucleocapsid assembles on Golgi membranes followed by budding of the virus into this organelle (6). The pleomorphic nature of RV virions has been a limiting factor in determining the structure of the virus particles.…”

mentioning

confidence: 99%

Rubella virus capsid protein structure and its role in virus assembly and infection

Prasad

Willows

Fokine

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…20 Rubella virus generally establishes a chronic nonlytic infection in the fetus and has the potential to infect any organs. 21,22 The rubella virus teratogenic process most probably begins when placental infection occurs during maternal viremia, leading to dissemination of the virus throughout the fetus. In addition, tissues from different organs of fetuses with CRS revealed teratogenic effects, such as reduced cell size and number compared with control, which was suggestive of mitotic inhibition or perhaps due to rubella induced chromosomal breaks.…”

Section: Newborn Follow-upmentioning

confidence: 99%

“…In addition, tissues from different organs of fetuses with CRS revealed teratogenic effects, such as reduced cell size and number compared with control, which was suggestive of mitotic inhibition or perhaps due to rubella induced chromosomal breaks. 21 Even when the fetus is infected, it survives in most cases; the pregnancy continues and premature births or stillbirths can occur. 3 In our results, the most common ultrasonographic prenatal rubella infection findings were heart and amniotic fluid anomalies.…”

Section: Newborn Follow-upmentioning

confidence: 99%

Prenatal diagnosis of congenital rubella infection in São Paulo

Curti

Figueiredo

Oliveira

et al. 2014

Rev. Assoc. Med. Bras.

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Objective: rubella during the early stages of pregnancy can lead to severe birth defects known as congenital rubella syndrome (CRS). Samples collected from pregnant women with symptoms and suspected of congenital rubella infection between 1996 and 2008 were analyzed. Methods: a total of 23 amniotic fluid samples, 16 fetal blood samples, 1 product of conception and 1 placenta were analyzed by serology and RT-PCR. Results: all patients presented positive serology for IgG / IgM antibodies to rubella virus. Among neonates, 16 were IgG-positive, 9 were IgM-positive and 4 were negative for both antibodies. Of the 25 samples analyzed in this study, 24 were positive by RT-PCR. Changes in ultrasound were found in 15 (60%) of 25 fetuses infected with rubella virus. Fetal death and miscarriage were reported in 10 (40%) of the 25 cases analyzed. The rubella virus was amplified by PCR in all fetuses with abnormal ultrasound compatible with rubella. Fetal death and abortion were reported in 10 of 25 cases analyzed. Conclusion: this study, based on primary maternal rubella infection definitely confirms the good sensitivity and specificity of RT-PCR using amniotic fluid and ultrasound. The results showed that molecular assays are important tools in the early diagnosis of rubella and congenital rubella syndrome.

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“…Rubella is a vaccine-preventable, mild rash-inducing viral disease with complications [2,3] that include a spectrum of birth defects in the developing foetus, especially if the viral infection is acquired in the early months (first trimester) of pregnancy [3][4][5][6]. Birth defects associated with rubella virus infection range from blindness, deafness, and congenital heart disease, to mental retardation and central nervous system (CNS) complications which are often collectively referred to as congenital rubella syndrome (CRS) [4,7,8].…”

Section: Introductionmentioning

confidence: 99%

Epidemiological evaluation of rubella virus infection among pregnant women in Ibadan, Nigeria

Adewumi

Olayinka

Olusola

et al. 2015

Preprint

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Rubella is a vaccine-preventable, mild rash-inducing viral disease with complications that include a spectrum of birth defects in the developing foetus, especially if the infection is acquired in the early months of pregnancy. Consequently, the primary objective of global rubella control programmes is prevention of congenital rubella infection and associated birth defects often collectively referred to as congenital rubella syndrome.Despite the availability of safe and effective vaccines, and elimination of rubella virus in many developed countries substantial commitment to rubella control has not been demonstrated in the developing countries. This study appraises immunity to rubella, and consequently makes appropriate recommendations aimed at facilitating effective control.A cross-sectional sero-surveillance study was carried out among 272 consenting ante-natal

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Molecular Biology of Rubella Virus

Cited by 250 publications

References 345 publications

Rubella virus capsid protein structure and its role in virus assembly and infection

Rubella virus capsid protein structure and its role in virus assembly and infection

Prenatal diagnosis of congenital rubella infection in São Paulo

Epidemiological evaluation of rubella virus infection among pregnant women in Ibadan, Nigeria

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