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https://www.readbyqxmd.com/read/29117563/outcomes-of-congenital-zika-disease-depend-on-timing-of-infection-and-maternal-fetal-interferon-action
#1
Jinling Chen, Yuejin Liang, Panpan Yi, Lanman Xu, Hal K Hawkins, Shannan L Rossi, Lynn Soong, Jiyang Cai, Ramkumar Menon, Jiaren Sun
Zika virus (ZIKV) infection during pregnancy in humans results in intrauterine growth restriction, spontaneous abortion, and microcephaly. Here, we found that fetus-derived type I interferon (IFN-I) signaling can enhance anti-ZIKV responses and provide clinical benefits to the fetus. Because IFN-λ shares signaling cascades and antiviral functions with IFN-I, we investigated the in vivo effects of IFN-λ in ZIKV-infected pregnant mice. IFN-λ administration during mid-pregnancy reduced ZIKV burden in maternal and fetal organs and alleviated placental injuries and fetal demise...
November 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28878771/coordinated-role-of-toll-like-receptor-3-and-retinoic-acid-inducible-gene-i-in-the-innate-response-of-bovine-endometrial-cells-to-virus
#2
Luisa C Carneiro, Carmen Bedford, Sarah Jacca, Alfonso Rosamilia, Vera F de Lima, Gaetano Donofrio, I Martin Sheldon, James G Cronin
Bovine herpesvirus-4 (BoHV-4) and bovine viral diarrhea virus (BVDV) infect the uterus of cattle, often resulting in reduced fertility, or abortion of the fetus, respectively. Here, exposure of primary bovine endometrial cells to BoHV-4 or BVDV modulated the production of inflammatory mediators. Viral pathogen-associated molecular patterns (PAMPs) are detected via pattern-recognition receptors (PRRs). However, the relative contribution of specific PRRs to innate immunity, during viral infection of the uterus, is unclear...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28869524/hpv16-e6-and-e7-upregulate-interferon-induced-antiviral-response-genes-isg15-and-ifit1-in-human-trophoblast-cells
#3
Lea M M Ambühl, Annemarie B Villadsen, Ulrik Baandrup, Karen Dybkær, Suzette Sørensen
Human papillomavirus (HPV) is suggested to infect trophoblasts in the placenta, and HPV infections are reported to be more prevalent in pregnancies with adverse outcomes. Results are however controversial, and studies investigating the molecular consequences of placental HPV infections are lacking. We studied HPV DNA localization in the placenta in cases of spontaneous abortion/spontaneous preterm delivery as well as in elective abortion/normal full-term delivery. Using in vitro assays, we investigated downstream effects of HPV16 E6 and E7 expression in trophoblast cells at the gene expression level in order to gain increased biological insight into the interaction between HPV and the cellular host...
September 3, 2017: Pathogens
https://www.readbyqxmd.com/read/28807293/sarcocystis-neurona-and-neospora-caninum-in-brazilian-opossums-didelphis-spp-molecular-investigation-and-in-vitro-isolation-of-sarcocystis-spp
#4
Leane S Q Gondim, Rogério F Jesus, Müller Ribeiro-Andrade, Jean C R Silva, Daniel B Siqueira, Maria F V Marvulo, Felipe M Aléssio, Jean-François Mauffrey, Fred S Julião, Elisa San Martin Mouriz Savani, Rodrigo M Soares, Luís F P Gondim
Sarcocystis neurona and Neospora spp. are protozoan parasites that induce neurological diseases in horses and other animal species. Opossums (Didelphis albiventris and Didelphis virginiana) are definitive hosts of S. neurona, which is the major cause of equine protozoal myeloencephalitis (EPM). Neospora caninum causes abortion in cattle and infects a wide range of animal species, while N. hughesi is known to induce neurologic disease in equids. The aims of this study were to investigate S. neurona and N. caninum in tissues from opossums in the northeastern Brazil, and to isolate Brazilian strains of Sarcocystis spp...
August 30, 2017: Veterinary Parasitology
https://www.readbyqxmd.com/read/28667332/viperin-is-an-important-host-restriction-factor-in-control-of-zika-virus-infection
#5
Kylie H Van der Hoek, Nicholas S Eyre, Byron Shue, Onruedee Khantisitthiporn, Kittirat Glab-Ampi, Jillian M Carr, Matthew J Gartner, Lachlan A Jolly, Paul Q Thomas, Fatwa Adikusuma, Tanja Jankovic-Karasoulos, Claire T Roberts, Karla J Helbig, Michael R Beard
Zika virus (ZIKV) infection has emerged as a global health threat and infection of pregnant women causes intrauterine growth restriction, spontaneous abortion and microcephaly in newborns. Here we show using biologically relevant cells of neural and placental origin that following ZIKV infection, there is attenuation of the cellular innate response characterised by reduced expression of IFN-β and associated interferon stimulated genes (ISGs). One such ISG is viperin that has well documented antiviral activity against a wide range of viruses...
June 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28625521/protective-efficacy-of-multivalent-replication-abortive-vaccine-strains-in-horses-against-african-horse-sickness-virus-challenge
#6
Valeria Lulla, Andres Losada, Sylvie Lecollinet, Adeline Kerviel, Thomas Lilin, Corinne Sailleau, Cecile Beck, Stephan Zientara, Polly Roy
African horse sickness virus (AHSV) is an orbivirus, a member of the Reoviridae family. Nine different serotypes have been described so far. AHSV is vectored by Culicoides spp. to equids, causing high mortality, particularly in horses, with considerable economic impacts. For development of a safe attenuated vaccine, we previously established an efficient reverse genetics (RG) system to generate Entry Competent Replication-Abortive (ECRA) virus strains, for all nine serotypes and demonstrated the vaccine potential of these strains in type I interferon receptor (IFNAR)-knockout mice...
July 24, 2017: Vaccine
https://www.readbyqxmd.com/read/28522204/peg-interferon-plus-nucleotide-analogue-treatment-versus-no-treatment-in-patients-with-chronic-hepatitis-b-with-a-low-viral-load-a-randomised-controlled-open-label-trial
#7
Annikki de Niet, Louis Jansen, Femke Stelma, Sophie B Willemse, Sjoerd D Kuiken, Sebastiaan Weijer, Carin M J van Nieuwkerk, Hans L Zaaijer, Richard Molenkamp, R Bart Takkenberg, Maarten Koot, Joanne Verheij, Ulrich Beuers, Hendrik W Reesink
BACKGROUND: Antiviral treatment is currently not recommended for patients with chronic hepatitis B with a low viral load. However, they might benefit from acquiring a functional cure (hepatitis B surface antigen [HBsAg] loss with or without formation of antibodies against hepatitis B surface antigen [anti-HBs]). We assessed HBsAg loss during peg-interferon-alfa-2a (peg-IFN) and nucleotide analogue combination therapy in patients with chronic hepatitis B with a low viral load. METHODS: In this randomised controlled, open-label trial, patients were enrolled from the Academic Medical Center (AMC), Amsterdam, Netherlands...
May 15, 2017: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28331165/tim-3-and-pd-1-regulate-cd8-t-cell-function-to-maintain-early-pregnancy-in-mice
#8
Yuan-Yuan Xu, Song-Cun Wang, Yi-Kong Lin, Da-Jin Li, Mei-Rong DU
During pregnancy, CD8(+) T cells are important regulators in the balance of fetal tolerance and antiviral immunity. T-cell immunoglobulin mucin-3 (Tim-3) and programmed cell death-1 (PD-1) are well-recognized negative co-stimulatory molecules involved in viral persistence and tumor metastasis. Here, we demonstrate that CD8(+) T cells co-expressing Tim-3 and PD-1 were down-regulated in the deciduae of female mice in abortion-prone matings compared with normal pregnant mice. In addition to their reduced numbers, the Tim-3(+)PD-1(+)CD8(+) T cells produced lower levels of the anti-inflammatory cytokines interleukin (IL)-4 and IL-10, as well as a higher level of the pro-inflammatory cytokine interferon (IFN)-γ, relative to those from normal pregnancy...
June 21, 2017: Journal of Reproduction and Development
https://www.readbyqxmd.com/read/28024153/hiv-1-blocks-the-signaling-adaptor-mavs-to-evade-antiviral-host-defense-after-sensing-of-abortive-hiv-1-rna-by-the-host-helicase-ddx3
#9
Sonja I Gringhuis, Nina Hertoghs, Tanja M Kaptein, Esther M Zijlstra-Willems, Ramin Sarrami-Fooroshani, Joris K Sprokholt, Nienke H van Teijlingen, Neeltje A Kootstra, Thijs Booiman, Karel A van Dort, Carla M S Ribeiro, Agata Drewniak, Teunis B H Geijtenbeek
The mechanisms by which human immunodeficiency virus 1 (HIV-1) avoids immune surveillance by dendritic cells (DCs), and thereby prevents protective adaptive immune responses, remain poorly understood. Here we showed that HIV-1 actively arrested antiviral immune responses by DCs, which contributed to efficient HIV-1 replication in infected individuals. We identified the RNA helicase DDX3 as an HIV-1 sensor that bound abortive HIV-1 RNA after HIV-1 infection and induced DC maturation and type I interferon responses via the signaling adaptor MAVS...
February 2017: Nature Immunology
https://www.readbyqxmd.com/read/27565347/vaginal-exposure-to-zika-virus-during-pregnancy-leads-to-fetal-brain-infection
#10
Laura J Yockey, Luis Varela, Tasfia Rakib, William Khoury-Hanold, Susan L Fink, Bernardo Stutz, Klara Szigeti-Buck, Anthony Van den Pol, Brett D Lindenbach, Tamas L Horvath, Akiko Iwasaki
Zika virus (ZIKV) can be transmitted sexually between humans. However, it is unknown whether ZIKV replicates in the vagina and impacts the unborn fetus. Here, we establish a mouse model of vaginal ZIKV infection and demonstrate that, unlike other routes, ZIKV replicates within the genital mucosa even in wild-type (WT) mice. Mice lacking RNA sensors or transcription factors IRF3 and IRF7 resulted in higher levels of local viral replication. Furthermore, mice lacking the type I interferon (IFN) receptor (IFNAR) became viremic and died of infection after a high-dose vaginal ZIKV challenge...
August 25, 2016: Cell
https://www.readbyqxmd.com/read/27462916/p53-elevation-in-human-cells-halt-sv40-infection-by-inhibiting-t-ag-expression
#11
Nir Drayman, Orly Ben-Nun-Shaul, Veronika Butin-Israeli, Rohit Srivastava, Ariel M Rubinstein, Caroline S Mock, Ela Elyada, Yinon Ben-Neriah, Galit Lahav, Ariella Oppenheim
SV40 large T-antigen (T-ag) has been known for decades to inactivate the tumor suppressor p53 by sequestration and additional mechanisms. Our present study revealed that the struggle between p53 and T-ag begins very early in the infection cycle. We found that p53 is activated early after SV40 infection and defends the host against the infection. Using live cell imaging and single cell analyses we found that p53 dynamics are variable among individual cells, with only a subset of cells activating p53 immediately after SV40 infection...
August 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27423203/alveolar-macrophages-can-control-respiratory-syncytial-virus-infection-in-the-absence-of-type-i-interferons
#12
Spyridon Makris, Monika Bajorek, Fiona J Culley, Michelle Goritzka, Cecilia Johansson
Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections. Immunity to RSV is initiated upon detection of the virus by pattern recognition receptors, such as RIG-I-like receptors. RIG-I-like receptors signal via MAVS to induce the synthesis of proinflammatory mediators, including type I interferons (IFNs), which trigger and shape antiviral responses and protect cells from infection. Alveolar macrophages (AMs) are amongst the first cells to encounter invading viruses and the ones producing type I IFNs...
2016: Journal of Innate Immunity
https://www.readbyqxmd.com/read/27411694/pregnancy-experience-nonclinical-studies-and-pregnancy-outcomes-in-the-daclizumab-clinical-study-program
#13
Ralf Gold, Dusan Stefoski, Krzysztof Selmaj, Eva Havrdova, Christopher Hurst, Joan Holman, Belen Tornesi, Surekha Akella, Peter McCroskery
INTRODUCTION: Multiple sclerosis (MS) is more common in women and can occur during childbearing years; thus, information on outcomes following exposure to MS therapy during pregnancy is important. No formal studies of daclizumab have been conducted in pregnant women. Here, we report available nonclinical and clinical data on pregnancy outcomes from the daclizumab clinical study program. METHODS: Reproductive and developmental toxicity studies were conducted in cynomolgus monkeys...
December 2016: Neurology and Therapy
https://www.readbyqxmd.com/read/27356904/immunization-with-attenuated-equine-herpesvirus-1-strain-kya-induces-innate-immune-responses-that-protect-mice-from-lethal-challenge
#14
Seong K Kim, Akhalesh K Shakya, Dennis J O'Callaghan
UNLABELLED: Equine herpesvirus 1 (EHV-1) is a major pathogen affecting equines worldwide. The virus causes respiratory disease, abortion, and, in some cases, neurological disease. EHV-1 strain KyA is attenuated in the mouse and equine, whereas wild-type strain RacL11 induces severe inflammation of the lung, causing infected mice to succumb at 4 to 6 days postinfection. Our previous results showed that KyA immunization protected CBA mice from pathogenic RacL11 challenge at 2 and 4 weeks postimmunization and that KyA infection elicited protective humoral and cell-mediated immune responses...
September 15, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27180225/zika-virus-infection-during-pregnancy-in-mice-causes-placental-damage-and-fetal-demise
#15
Jonathan J Miner, Bin Cao, Jennifer Govero, Amber M Smith, Estefania Fernandez, Omar H Cabrera, Charise Garber, Michelle Noll, Robyn S Klein, Kevin K Noguchi, Indira U Mysorekar, Michael S Diamond
Zika virus (ZIKV) infection in pregnant women causes intrauterine growth restriction, spontaneous abortion, and microcephaly. Here, we describe two mouse models of placental and fetal disease associated with in utero transmission of ZIKV. Female mice lacking type I interferon signaling (Ifnar1(-/-)) crossed to wild-type (WT) males produced heterozygous fetuses resembling the immune status of human fetuses. Maternal inoculation at embryonic day 6.5 (E6.5) or E7.5 resulted in fetal demise that was associated with ZIKV infection of the placenta and fetal brain...
May 19, 2016: Cell
https://www.readbyqxmd.com/read/27160972/effects-of-cytokines-and-tlr-ligands-on-the-production-of-plgf-and-svegfr1-in-primary-trophoblasts
#16
Erina Kato, Tatsuo Yamamoto, Fumihisa Chishima
AIM: Cytokines such as tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) play an important role in maintaining pregnancy. Toll-like receptors (TLRs) have also been associated with innate immune responses during pregnancy. Placenta growth factor (PlGF) is one of the angiogenic factors and soluble vascular endothelial growth factor receptor 1 (sVEGFR1) is one of the antiangiogenic factors that regulate PlGF function. To elucidate the effects of cytokines and TLR ligands on the production of angiogenic and antiangiogenic factors in trophoblasts, we examined the production of PlGF and sVEGFR1 from trophoblasts following stimulation with cytokines and TLR ligands...
2017: Gynecologic and Obstetric Investigation
https://www.readbyqxmd.com/read/27147487/therapeutic-effects-of-wharton-jelly-derived-mesenchymal-stem-cells-on-rat-abortion-models
#17
Xiaojing Chen, Xiaoqing Yang, Rongrong Wu, Weiwei Chen, Huihui Xie, Xia Qian, Yuquan Zhang
AIM: The aim of this study was to investigate the therapeutic effects and mechanism of Wharton jelly-derived mesenchymal stem cells (WJ-MSC) in a spontaneous-abortion rat model. METHODS: An abortion model was established using intravenous injection of bromocriptine. WJ-MSC were isolated and cultured from Wharton jelly of the human umbilical cord. The pathologic changes of placenta decidual tissues were observed after hematoxylin-eosin staining. The embryo absorption rate was counted...
August 2016: Journal of Obstetrics and Gynaecology Research
https://www.readbyqxmd.com/read/27090619/equine-herpesvirus-1-infection-disrupts-interferon-regulatory-factor-3-irf-3-signaling-pathways-in-equine-endothelial-cells
#18
Sanjay Sarkar, Udeni B R Balasuriya, David W Horohov, Thomas M Chambers
Equine herpesvirus-1 (EHV-1) is a major respiratory viral pathogen of horses, causing upper respiratory tract disease, abortion, neonatal death, and neurological disease that may lead to paralysis and death. EHV-1 replicates initially in the respiratory epithelium and then spreads systemically to endothelial cells lining the small blood vessels in the uterus and spinal cord leading to abortion and EHM in horses. Like other herpesviruses, EHV-1 employs a variety of mechanisms for immune evasion including suppression of type-I interferon (IFN) production in equine endothelial cells (EECs)...
May 2016: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/26920382/interferon-beta-exposure-during-first-trimester-is-safe-in-women-with-multiple-sclerosis-a-prospective-cohort-study-from-the-german-multiple-sclerosis-and-pregnancy-registry
#19
Sandra Thiel, Annette Langer-Gould, Milena Rockhoff, Aiden Haghikia, Annette Queisser-Wahrendorf, Ralf Gold, Kerstin Hellwig
BACKGROUND: Available data suggest that pregnancy exposure to interferon-beta might result in lower mean birth weight and preterm birth. OBJECTIVE: To determine the effect of interferon-beta exposure during pregnancy on pregnancy outcomes in multiple sclerosis patients. METHODS: We compared the pregnancy outcomes of women exposed to interferon-beta with pregnancies unexposed to disease-modifying therapies. Women were enrolled into the German Multiple Sclerosis and Pregnancy Registry...
May 2016: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/26764007/trim5%C3%AE-degradation-via-autophagy-is-not-required-for-retroviral-restriction
#20
Sabrina Imam, Sarah Talley, Rachel S Nelson, Adarsh Dharan, Christopher O'Connor, Thomas J Hope, Edward M Campbell
UNLABELLED: TRIM5α is an interferon-inducible retroviral restriction factor that prevents infection by inducing the abortive disassembly of capsid cores recognized by its C-terminal PRY/SPRY domain. The mechanism by which TRIM5α mediates the disassembly of viral cores is poorly understood. Previous studies demonstrated that proteasome inhibitors abrogate the ability of TRIM5α to induce premature core disassembly and prevent reverse transcription; however, viral infection is still inhibited, indicating that the proteasome is partially involved in the restriction process...
January 13, 2016: Journal of Virology
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