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Thesis ; Online: Crossing barriers

Oymans, Judith

How neglected arboviruses journey through the placenta

2021

Abstract: The Schmallenberg outbreak of 2011 and the Zika virus outbreak of 2015 have demonstrated the devastating consequences of epizootics and epidemics caused by new or emerging arboviruses with the ability to transmit vertically in both humans and animals. ... ...

Abstract	The Schmallenberg outbreak of 2011 and the Zika virus outbreak of 2015 have demonstrated the devastating consequences of epizootics and epidemics caused by new or emerging arboviruses with the ability to transmit vertically in both humans and animals. Our poor preparedness has highlighted a knowledge gap in our understanding of the mechanisms underlying vertical transmission and the pathology that leads to abortion, stillbirth or congenital malformations. It is important that we bridge this knowledge gap by studying neglected arboviruses that exhibit vertical transmission so that we are able to identify and prioritise potential threats for animal and human health in the future. Characterising the mechanisms that underlie the pathophysiology of these viruses could also aid the development of efficient countermeasures. In this thesis, I elucidated the transmission routes of arboviruses over the placental barrier to the foetuses by identifying primary target cells and tissues. A first step towards being able to study these viruses is to develop protocols and tools that can also be used for the development of diagnostic procedures.
Keywords	Life Science
Language	English
Publisher	Wageningen University
Publishing country	nl
Document type	Thesis ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Initiation, Elongation, and Realignment during Influenza Virus mRNA Synthesis.

Te Velthuis, Aartjan J W / Oymans, Judith

Journal of virology

2018 Volume 92, Issue 3

Abstract: The RNA-dependent RNA polymerase (RdRp) of the influenza A virus replicates and transcribes the viral genome segments in the nucleus of the host cell. To transcribe these viral genome segments, the RdRp "snatches" capped RNA oligonucleotides from nascent ...

Abstract	The RNA-dependent RNA polymerase (RdRp) of the influenza A virus replicates and transcribes the viral genome segments in the nucleus of the host cell. To transcribe these viral genome segments, the RdRp "snatches" capped RNA oligonucleotides from nascent host cell mRNAs and aligns these primers to the ultimate or penultimate nucleotide of the segments for the initiation of viral mRNA synthesis. It has been proposed that this initiation process is not processive and that the RdRp uses a prime-realign mechanism during transcription. Here we provide
MeSH term(s)	Animals ; HEK293 Cells ; Humans ; Influenza A virus/genetics ; Influenza A virus/physiology ; RNA, Messenger/metabolism ; RNA, Viral/metabolism ; RNA-Dependent RNA Polymerase/chemistry ; RNA-Dependent RNA Polymerase/metabolism ; Sf9 Cells ; Transcription, Genetic ; Viral Proteins/metabolism
Chemical Substances	RNA, Messenger ; RNA, Viral ; Viral Proteins ; RNA-Dependent RNA Polymerase (EC 2.7.7.48)
Language	English
Publishing date	2018-01-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.01775-17
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: A Mechanism for Priming and Realignment during Influenza A Virus Replication.

Oymans, Judith / Te Velthuis, Aartjan J W

Journal of virology

2018 Volume 92, Issue 3

Abstract: The influenza A virus genome consists of eight segments of single-stranded RNA. These segments are replicated and transcribed by a viral RNA-dependent RNA polymerase (RdRp) that is made up of the influenza virus proteins PB1, PB2, and PA. To copy the ... ...

Abstract	The influenza A virus genome consists of eight segments of single-stranded RNA. These segments are replicated and transcribed by a viral RNA-dependent RNA polymerase (RdRp) that is made up of the influenza virus proteins PB1, PB2, and PA. To copy the viral RNA (vRNA) genome segments and the cRNA segments, the replicative intermediate of viral replication, the RdRp must use two promoters and two different
MeSH term(s)	DNA-Directed RNA Polymerases/metabolism ; Genome, Viral ; HEK293 Cells ; Humans ; Influenza A virus/genetics ; Influenza A virus/physiology ; Promoter Regions, Genetic ; RNA, Viral/genetics ; RNA-Dependent RNA Polymerase/genetics ; Transcription, Genetic ; Viral Proteins/genetics ; Virus Replication
Chemical Substances	RNA, Viral ; Viral Proteins ; RNA-Dependent RNA Polymerase (EC 2.7.7.48) ; DNA-Directed RNA Polymerases (EC 2.7.7.6)
Language	English
Publishing date	2018-01-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.01773-17
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

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Article: Early Pathogenesis of Wesselsbron Disease in Pregnant Ewes

Oymans, Judith / van Keulen, Lucien / Wichgers Schreur, Paul J / Kortekaas, Jeroen

Pathogens. 2020 May 13, v. 9, no. 5

2020

Abstract: Wesselsbron virus (WSLV) is a neglected, mosquito-borne flavivirus that is endemic to the African continent. The virus is teratogenic to ruminants and causes a self-limiting febrile illness in humans. Wesselsbron disease manifests with similar clinical ... ...

Abstract	Wesselsbron virus (WSLV) is a neglected, mosquito-borne flavivirus that is endemic to the African continent. The virus is teratogenic to ruminants and causes a self-limiting febrile illness in humans. Wesselsbron disease manifests with similar clinical signs and occurs in the same areas under the same climatic conditions as Rift Valley fever, which is therefore included in the differential diagnosis. Although the gross pathology of WSLV infection in pregnant ewes is reported in literature, the pathogenesis that leads to stillbirths, congenital malformations and abortion has remained undescribed. In the present study, pregnant ewes were inoculated with WSLV and subjected to detailed clinical- and histopathology 8 days later. The virus was mainly detected in foetal trophoblasts of the placenta and in neural progenitor cells, differentiated neurons, oligodendrocytes, microglia and astrocytes. Our study demonstrates that WSLV efficiently crosses the maternal–foetal interface and is highly neuroinvasive in the ovine foetus.
Keywords	Rift Valley fever ; Wesselsbron virus ; astrocytes ; climatic factors ; congenital abnormalities ; crossing ; ewes ; fetal death ; fetus ; histopathology ; humans ; infection ; literature ; neural stem cells ; neurons ; oligodendroglia ; pathogenesis ; pathogens ; placenta ; signs and symptoms (animals and humans) ; teratogenicity ; viruses ; Africa
Language	English
Dates of publication	2020-0513
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
Note	NAL-light
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens9050373
Database	NAL-Catalogue (AGRICOLA)

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Article: Early Pathogenesis of Wesselsbron Disease in Pregnant Ewes.

Oymans, Judith / van Keulen, Lucien / Wichgers Schreur, Paul J / Kortekaas, Jeroen

Pathogens (Basel, Switzerland)

2020 Volume 9, Issue 5

Abstract	Wesselsbron virus (WSLV) is a neglected, mosquito-borne flavivirus that is endemic to the African continent. The virus is teratogenic to ruminants and causes a self-limiting febrile illness in humans. Wesselsbron disease manifests with similar clinical signs and occurs in the same areas under the same climatic conditions as Rift Valley fever, which is therefore included in the differential diagnosis. Although the gross pathology of WSLV infection in pregnant ewes is reported in literature, the pathogenesis that leads to stillbirths, congenital malformations and abortion has remained undescribed. In the present study, pregnant ewes were inoculated with WSLV and subjected to detailed clinical- and histopathology 8 days later. The virus was mainly detected in foetal trophoblasts of the placenta and in neural progenitor cells, differentiated neurons, oligodendrocytes, microglia and astrocytes. Our study demonstrates that WSLV efficiently crosses the maternal-foetal interface and is highly neuroinvasive in the ovine foetus.
Language	English
Publishing date	2020-05-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens9050373
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Shuni Virus Replicates at the Maternal-Fetal Interface of the Ovine and Human Placenta.

Oymans, Judith / van Keulen, Lucien / Vermeulen, Guus M / Wichgers Schreur, Paul J / Kortekaas, Jeroen

Pathogens (Basel, Switzerland)

2020 Volume 10, Issue 1

Abstract: Shuni virus (SHUV) is a neglected teratogenic and neurotropic orthobunyavirus that was discovered in the 1960s in Nigeria and was subsequently detected in South Africa, Zimbabwe, and Israel. The virus was isolated from field-collected biting midges and ... ...

Abstract	Shuni virus (SHUV) is a neglected teratogenic and neurotropic orthobunyavirus that was discovered in the 1960s in Nigeria and was subsequently detected in South Africa, Zimbabwe, and Israel. The virus was isolated from field-collected biting midges and mosquitoes and shown to disseminate efficiently in laboratory-reared biting midges, suggesting that members of the families
Language	English
Publishing date	2020-12-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens10010017
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: SARS-CoV-2 nucleocapsid protein inhibits the PKR-mediated integrated stress response through RNA-binding domain N2b.

Aloise, Chiara / Schipper, Jelle G / van Vliet, Arno / Oymans, Judith / Donselaar, Tim / Hurdiss, Daniel L / de Groot, Raoul J / van Kuppeveld, Frank J M

PLoS pathogens

2023 Volume 19, Issue 8, Page(s) e1011582

Abstract: The nucleocapsid protein N of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enwraps and condenses the viral genome for packaging but is also an antagonist of the innate antiviral defense. It suppresses the integrated stress response (ISR), ...

Abstract	The nucleocapsid protein N of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enwraps and condenses the viral genome for packaging but is also an antagonist of the innate antiviral defense. It suppresses the integrated stress response (ISR), purportedly by interacting with stress granule (SG) assembly factors G3BP1 and 2, and inhibits type I interferon responses. To elucidate its mode of action, we systematically deleted and over-expressed distinct regions and domains. We show that N via domain N2b blocks PKR-mediated ISR activation, as measured by suppression of ISR-induced translational arrest and SG formation. N2b mutations that prevent dsRNA binding abrogate these activities also when introduced in the intact N protein. Substitutions reported to block post-translation modifications of N or its interaction with G3BP1/2 did not have a detectable additive effect. In an encephalomyocarditis virus-based infection model, N2b - but not a derivative defective in RNA binding-prevented PKR activation, inhibited β-interferon expression and promoted virus replication. Apparently, SARS-CoV-2 N inhibits innate immunity by sequestering dsRNA to prevent activation of PKR and RIG-I-like receptors. Similar observations were made for the N protein of human coronavirus 229E, suggesting that this may be a general trait conserved among members of other orthocoronavirus (sub)genera.
MeSH term(s)	Humans ; SARS-CoV-2/genetics ; DNA Helicases ; COVID-19 ; Poly-ADP-Ribose Binding Proteins ; RNA Helicases ; RNA Recognition Motif Proteins/genetics ; RNA-Binding Motifs ; Encephalomyocarditis virus
Chemical Substances	DNA Helicases (EC 3.6.4.-) ; Poly-ADP-Ribose Binding Proteins ; RNA Helicases (EC 3.6.4.13) ; RNA Recognition Motif Proteins ; G3BP1 protein, human (EC 3.6.4.12)
Language	English
Publishing date	2023-08-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7374
ISSN (online)	1553-7374
ISSN	1553-7374
DOI	10.1371/journal.ppat.1011582
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Rift Valley fever virus targets the maternal-foetal interface in ovine and human placentas.

Oymans, Judith / Wichgers Schreur, Paul J / van Keulen, Lucien / Kant, Jet / Kortekaas, Jeroen

PLoS neglected tropical diseases

2020 Volume 14, Issue 1, Page(s) e0007898

Abstract: Background: Rift Valley fever virus (RVFV) is an arbovirus of the order Bunyavirales that causes severe disease in ruminants and humans. Outbreaks in sheep herds are characterised by newborn fatalities and abortion storms. The association of RVFV ... ...

Abstract	Background: Rift Valley fever virus (RVFV) is an arbovirus of the order Bunyavirales that causes severe disease in ruminants and humans. Outbreaks in sheep herds are characterised by newborn fatalities and abortion storms. The association of RVFV infections with abortions of ovines and other ruminants is well recognized, whereas the pathology resulting in abortion has remained undescribed. Accumulating evidence suggests that RVFV is abortogenic in humans as well, warranting more research on the interaction of RVFV with the ruminant and human placenta. Methodology/principal findings: Pregnant ewes were inoculated with a highly virulent strain of RVFV and necropsied at different days post infection. Tissues were collected and analysed by PCR, virus isolation, and immunohistochemistry. The results show that RVFV replicates efficiently in maternal placental epithelial cells before the virus infects foetal trophoblasts. Moreover, the virus was shown to bypass the maternal epithelial cell layer by directly targeting foetal trophoblasts in the haemophagous zone, a region of the ovine placenta where maternal blood is in direct contact with foetal cells. Abortion was associated with widespread necrosis of placental tissues accompanied with severe haemorrhages. Experiments with human placental explants revealed that the same virus strain replicates efficiently in both cyto- and syncytiotrophoblasts. Conclusions/significance: This study demonstrates that RVFV targets the foetal-maternal interface in both ovine and human placentas. The virus was shown to cross the ovine placental barrier via two distinct routes, ultimately resulting in placental and foetal demise followed by abortion. Our finding that RVFV replicates efficiently in human trophoblasts underscores the risk of RVFV infection for human pregnancy.
MeSH term(s)	Animals ; Female ; Humans ; Infant, Newborn ; Infant, Newborn, Diseases/veterinary ; Infant, Newborn, Diseases/virology ; Infectious Disease Transmission, Vertical/veterinary ; Placenta/virology ; Pregnancy ; Rift Valley Fever/transmission ; Rift Valley Fever/virology ; Rift Valley fever virus/genetics ; Rift Valley fever virus/isolation & purification ; Rift Valley fever virus/physiology ; Sheep ; Sheep Diseases/virology
Language	English
Publishing date	2020-01-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2429704-5
ISSN	1935-2735 ; 1935-2727
ISSN (online)	1935-2735
ISSN	1935-2727
DOI	10.1371/journal.pntd.0007898
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Shuni virus replicates at the maternal-fetal interface of the ovine and human placenta

Oymans, Judith / van Keulen, Lucien / Vermeulen, Guus M. / Wichgers Schreur, Paul J. / Kortekaas, Jeroen

Pathogens

2021 Volume 10, Issue 1

Abstract	Shuni virus (SHUV) is a neglected teratogenic and neurotropic orthobunyavirus that was discovered in the 1960s in Nigeria and was subsequently detected in South Africa, Zimbabwe, and Israel. The virus was isolated from field-collected biting midges and mosquitoes and shown to disseminate efficiently in laboratory-reared biting midges, suggesting that members of the families Culicidae and Ceratopogonidae may function as vectors. SHUV infections have been associated with severe neurological disease in horses, a variety of wildlife species, and domesticated ruminants. SHUV infection of ruminants is additionally associated with abortion, stillbirth, and congenital malformations. The detection of antibodies in human sera also suggests that the virus may have zoonotic potential. To understand how SHUV crosses the ruminant placenta, we here infected pregnant ewes and subsequently performed detailed clinical-and histopathological examination of placental tissue. We found that SHUV targets both maternal epithelial cells and fetal trophoblasts, that together form the maternal-fetal interface of the ovine placenta. Experiments with human placental explants, furthermore, revealed replication of SHUV in syncytiotrophoblasts, which are generally highly resistant to virus infections. Our findings provide novel insights into vertical transmission of SHUV in sheep and call for research on the potential risk of SHUV infection during human pregnancies.
Keywords	Explants ; Placenta ; Pregnant ewes ; Shuni virus ; Vertical transmission ; Zoonosis
Subject code	610
Language	English
Publishing country	nl
Document type	Article ; Online
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Initiation, elongation, and realignment during influenza virus mRNA synthesis

te Velthuis, Aartjan J.W. / Oymans, Judith

Journal of Virology

2018 Volume 92, Issue 3

Abstract	The RNA-dependent RNA polymerase (RdRp) of the influenza A virus replicates and transcribes the viral genome segments in the nucleus of the host cell. To transcribe these viral genome segments, the RdRp "snatches" capped RNA oligonucleotides from nascent host cell mRNAs and aligns these primers to the ultimate or penultimate nucleotide of the segments for the initiation of viral mRNA synthesis. It has been proposed that this initiation process is not processive and that the RdRp uses a prime-realign mechanism during transcription. Here we provide in vitro evidence for the existence of this transcriptional prime-realign mechanism but show that it functions efficiently only for primers that are short or cannot stably base pair with the template. In addition, we demonstrate that transcriptional elongation is dependent on the priming loop of the PB1 subunit of the RdRp. We propose that the prime-realign mechanism may be used to rescue abortive transcription initiation events or cope with sequence variation among primers. Overall, these observations advance our mechanistic understanding of how influenza A virus initiates transcription correctly and efficiently.
Keywords	Influenza A virus ; Priming loop ; RNA-dependent RNA polymerase ; Realignment ; Replication ; Transcription ; Viral transcription
Subject code	570
Language	English
Publishing country	nl
Document type	Article ; Online
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

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