scholarly journals Impact of prior flavivirus immunity on Zika virus infection in rhesus macaques

2017 ◽  
Vol 13 (8) ◽  
pp. e1006487 ◽  
Author(s):  
Michael K. McCracken ◽  
Gregory D. Gromowski ◽  
Heather L. Friberg ◽  
Xiaoxu Lin ◽  
Peter Abbink ◽  
...  
Keyword(s):  
Virus Infection ◽  
Zika Virus ◽  
Rhesus Macaques ◽  
Zika Virus Infection

scholarly journals Zika virus infection in pregnant rhesus macaques causes placental dysfunction and immunopathology

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Alec J. Hirsch ◽  
Victoria H. J. Roberts ◽  
Peta L. Grigsby ◽  
Nicole Haese ◽  
Matthias C. Schabel ◽  
...  
Keyword(s):  
Virus Infection ◽  
Zika Virus ◽  
Rhesus Macaques ◽  
Placental Dysfunction ◽  
Zika Virus Infection

scholarly journals A direct-acting antiviral drug abrogates viremia in Zika virus–infected rhesus macaques

2020 ◽  
Vol 12 (547) ◽  
pp. eaau9135 ◽  
Author(s):  
So-Yon Lim ◽  
Christa E. Osuna ◽  
Katharine Best ◽  
Ray Taylor ◽  
Elsa Chen ◽  
...  
Keyword(s):  
Virus Infection ◽  
Zika Virus ◽  
Rhesus Macaques ◽  
Antiviral Drug ◽  
Neurological Complications ◽  
Direct Acting Antiviral ◽  
Antiviral Efficacy ◽  
Zika Virus Infection ◽  
Dosing Strategies ◽  
Direct Acting

Zika virus infection in humans has been associated with serious reproductive and neurological complications. At present, no protective antiviral drug treatment is available. Here, we describe the testing and evaluation of the antiviral drug, galidesivir, against Zika virus infection in rhesus macaques. We conducted four preclinical studies in rhesus macaques to assess the safety, antiviral efficacy, and dosing strategies for galidesivir (BCX4430) against Zika virus infection. We treated 70 rhesus macaques infected by various routes with the Puerto Rico or Thai Zika virus isolates. We evaluated galidesivir administered as early as 90 min and as late as 72 hours after subcutaneous Zika virus infection and as late as 5 days after intravaginal infection. We evaluated the efficacy of a range of galidesivir doses with endpoints including Zika virus RNA in plasma, saliva, urine, and cerebrospinal fluid. Galidesivir dosing in rhesus macaques was safe and offered postexposure protection against Zika virus infection. Galidesivir exhibited favorable pharmacokinetics with no observed teratogenic effects in rats or rabbits at any dose tested. The antiviral efficacy of galidesivir observed in the blood and central nervous system of infected animals warrants continued evaluation of this compound for the treatment of flaviviral infections.

scholarly journals Zika Virus infection of rhesus macaques leads to viral persistence in multiple tissues

2017 ◽  
Vol 13 (3) ◽  
pp. e1006219 ◽  
Author(s):  
Alec J. Hirsch ◽  
Jessica L. Smith ◽  
Nicole N. Haese ◽  
Rebecca M. Broeckel ◽  
Christopher J. Parkins ◽  
...  
Keyword(s):  
Virus Infection ◽  
Zika Virus ◽  
Rhesus Macaques ◽  
Viral Persistence ◽  
Zika Virus Infection

scholarly journals A rhesus macaque model of Asia lineage Zika virus infection

2016 ◽  
Author(s):  
Dawn M. Dudley ◽  
Matthew T. Aliota ◽  
Emma Mohr ◽  
Andrea M. Weiler ◽  
Gabrielle Lehrer-Brey ◽  
...  
Keyword(s):  
T Cells ◽  
Virus Infection ◽  
Zika Virus ◽  
Neutralizing Antibodies ◽  
Rhesus Macaques ◽  
Case Reports ◽  
Viral Rna ◽  
Zika Virus Infection ◽  
Homologous Virus ◽  
Asian Lineage

Infection with Asian lineage Zika virus has been associated with Guillain-Barré syndrome and fetal abnormalities1–4, but the mechanisms and risk factors for these outcomes remain unknown. Here we show that rhesus macaques are susceptible to infection by an Asian-lineage virus closely related to strains currently circulating in the Americas. Following subcutaneous inoculation, Zika virus RNA was detected in plasma one day post-infection (dpi) in all animals (N = 8, including 2 animals infected during the first trimester of pregnancy). Plasma viral loads peaked above 1 × 105viral RNA copies/mL in seven of eight animals. Viral RNA was also present in saliva, urine, and cerebrospinal fluid (CSF), consistent with case reports from infected humans. Viral RNA was cleared from plasma and urine by 21 dpi in non-pregnant animals. In contrast, both pregnant animals remained viremic longer, up to 57 days. In all animals, infection was associated with transient increases in proliferating natural killer cells, CD8+ T cells, CD4+ T cells, and plasmablasts. Neutralizing antibodies were detected in all animals by 21 dpi. Rechallenge of three non-pregnant animals with the Asian-lineage Zika virus 10 weeks after the initial challenge resulted in no detectable virus replication, suggesting that primary Zika virus infection elicits protective immunity against homologous virus strains. These data establish that Asian-lineage Zika virus infection of rhesus macaques provides a relevant animal model for studying pathogenesis in pregnant and non-pregnant individuals and evaluating potential interventions against human infection, including during pregnancy.

scholarly journals Correction: Zika Virus infection of rhesus macaques leads to viral persistence in multiple tissues

2017 ◽  
Vol 13 (4) ◽  
pp. e1006317 ◽  
Author(s):  
Alec J. Hirsch ◽  
Jessica L. Smith ◽  
Nicole N. Haese ◽  
Rebecca M. Broeckel ◽  
Christopher J. Parkins ◽  
...  
Keyword(s):  
Virus Infection ◽  
Zika Virus ◽  
Rhesus Macaques ◽  
Viral Persistence ◽  
Zika Virus Infection

Congenital Zika Virus Infection Paradigm: What is in the Wardrobe? A Narrative Review

2019 ◽  
Vol 1 (1) ◽  
pp. 49-56
Author(s):  
Mariam M. Mirambo ◽  
Lucas Matemba ◽  
Mtebe Majigo ◽  
Stephen E. Mshana
Keyword(s):  
Virus Infection ◽  
Neural Tube ◽  
Zika Virus ◽  
English Language ◽  
Case Reports ◽  
Case Series ◽  
Epidemiological Studies ◽  
Ocular Manifestations ◽  
Zika Virus Infection ◽  
N 93

Background: Zika virus infection during pregnancy has been recently associated with congenital microcephaly and other severe neural tube defects. However, the magnitude of confirmed cases and the scope of these anomalies have not been extensively documented. This review focuses on the magnitude of laboratory-confirmed congenital Zika virus cases among probable cases and describing the patterns of congenital anomalies allegedly caused by the Zika virus, information which will inform further research in this area. Methods: We conducted a literature search for English-language articles about congenital Zika virus infection using online electronic databases (PubMed/MEDLINE, POPLINE, Embase, Google Scholar, and Web of Knowledge). The search terms used were, “zika”, “pregnancy”, [year], “microcephaly”, “infants”, “children”, “neonates”, “foetuses”, “neural tube defect”, and “CNS manifestations” in different combinations. All articles reporting cases or case series between January 2015 and December 2016 were included. Data were entered into a Microsoft Excel database and analysed to obtain proportions of the confirmed cases and patterns of anomalies. Results: A total of 24 articles (11 case series, 9 case reports, and 4 others) were found to be eligible and included in this review. These articles reported 919 cases, with or without microcephaly, presumed to have congenital Zika virus infection. Of these cases, 884 (96.2%) had microcephaly. Of the 884 cases of microcephaly, 783 (88.6%) were tested for Zika virus infection, and 216 (27.6%; 95% confidence interval, 24.5% to 30.8%) were confirmed to be Zika virus-positive. In addition to microcephaly, other common abnormalities reported – out of 442 cases investigated – were calcifications of brain tissue (n=240, 54.3%), ventriculomegaly (n=93, 20.8%), cerebellar hypoplasia (n=52, 11.7%), and ocular manifestations (n=46, 10.4%). Conclusion: Based on the available literature, Zika virus infection during pregnancy might lead to a wide array of outcomes other than microcephaly. There is a need for more epidemiological studies in Zika-endemic areas, particularly in Africa, to ascertain the role of Zika virus in causing congenital neurological defects.

Congenital Zika Virus Infection Paradigm: What is in the Wardrobe? A Narrative Review

2019 ◽  
Vol 1 (1) ◽  
pp. 49-56
Author(s):  
Mariam M. Mirambo ◽  
Lucas Matemba ◽  
Mtebe Majigo ◽  
Stephen E. Mshana
Keyword(s):  
Virus Infection ◽  
Neural Tube ◽  
Zika Virus ◽  
English Language ◽  
Case Reports ◽  
Case Series ◽  
Epidemiological Studies ◽  
Ocular Manifestations ◽  
Zika Virus Infection ◽  
N 93

Background: Zika virus infection during pregnancy has been recently associated with congenital microcephaly and other severe neural tube defects. However, the magnitude of confirmed cases and the scope of these anomalies have not been extensively documented. This review focuses on the magnitude of laboratory-confirmed congenital Zika virus cases among probable cases and describing the patterns of congenital anomalies allegedly caused by the Zika virus, information which will inform further research in this area. Methods: We conducted a literature search for English-language articles about congenital Zika virus infection using online electronic databases (PubMed/MEDLINE, POPLINE, Embase, Google Scholar, and Web of Knowledge). The search terms used were, “zika”, “pregnancy”, [year], “microcephaly”, “infants”, “children”, “neonates”, “foetuses”, “neural tube defect”, and “CNS manifestations” in different combinations. All articles reporting cases or case series between January 2015 and December 2016 were included. Data were entered into a Microsoft Excel database and analysed to obtain proportions of the confirmed cases and patterns of anomalies. Results: A total of 24 articles (11 case series, 9 case reports, and 4 others) were found to be eligible and included in this review. These articles reported 919 cases, with or without microcephaly, presumed to have congenital Zika virus infection. Of these cases, 884 (96.2%) had microcephaly. Of the 884 cases of microcephaly, 783 (88.6%) were tested for Zika virus infection, and 216 (27.6%; 95% confidence interval, 24.5% to 30.8%) were confirmed to be Zika virus-positive. In addition to microcephaly, other common abnormalities reported – out of 442 cases investigated – were calcifications of brain tissue (n=240, 54.3%), ventriculomegaly (n=93, 20.8%), cerebellar hypoplasia (n=52, 11.7%), and ocular manifestations (n=46, 10.4%). Conclusion: Based on the available literature, Zika virus infection during pregnancy might lead to a wide array of outcomes other than microcephaly. There is a need for more epidemiological studies in Zika-endemic areas, particularly in Africa, to ascertain the role of Zika virus in causing congenital neurological defects.

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