Macaque monkeys in Zika virus research: 1947–present

Newman, Christina M.; Friedrich, Thomas C.; O’Connor, David H.

doi:10.1016/j.coviro.2017.06.011

Cited by 35 publications

(37 citation statements)

References 83 publications

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“…In NHP models, first trimester infection most frequently results in fetal demise and reduced fetal development even in asymptomatic mothers, while second trimester infections tend to produce fetuses with higher viral loads but greater fetal viability [8][9][10]. In all NHP models, fetal pathology ranges from mild to severe manifestations, consistent with Congenital Zika Syndrome (CZS) seen in humans [11][12][13][14][15][16]. While NHP models of ZIKV infection during pregnancy recapitulate human infection, other outbred host models can serve as surrogates when ethical and economic constraints create obstacles to the use of NHP.Sheep offer a unique animal model for translational biomedical research, and have long been used as a model for human pregnancy and fetal development due to longer gestation and comparably staged rates of fetal development [17,18].…”

mentioning

confidence: 89%

Experimental Infection of Mid-Gestation Pregnant Female and Intact Male Sheep with Zika Virus

Schwarz

Oliveira

Bonfante

et al. 2020

Viruses

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Zika virus (ZIKV) is an arbovirus that causes birth defects, persistent male infection, and sexual transmission in humans. The purpose of this study was to continue the development of an ovine ZIKV infection model; thus, two experiments were undertaken. In the first experiment, we built on previous pregnant sheep experiments by developing a mid-gestation model of ZIKV infection. Four pregnant sheep were challenged with ZIKV at 57-64 days gestation; two animals served as controls. After 13-15 days (corresponding with 70-79 days of gestation), one control and two infected animals were euthanized; the remaining animals were euthanized at 20-22 days post-infection (corresponding with 77-86 days of gestation). In the second experiment, six sexually mature, intact, male sheep were challenged with ZIKV and two animals served as controls. Infected animals were serially euthanized on days 2-6 and day 9 post-infection with the goal of isolating ZIKV from the male reproductive tract. In the mid-gestation study, virus was detected in maternal placenta and spleen, and in fetal organs, including the brains, spleens/liver, and umbilicus of infected fetuses. Fetuses from infected animals had visibly misshapen heads and morphometrics revealed significantly smaller head sizes in infected fetuses when compared to controls. Placental pathology was evident in infected dams. In the male experiment, ZIKV was detected in the spleen, liver, testes/epididymides, and accessory sex glands of infected animals. Results from both experiments indicate that mid-gestation ewes can be infected with ZIKV with subsequent disruption of fetal development and that intact male sheep are susceptible to ZIKV infection and viral dissemination and replication occurs in highly vascular tissues (including those of the male reproductive tract).Viruses 2020, 12, 291 2 of 23 and negative gestational outcomes when infection occurs during pregnancy. In humans, ZIKV is believed to result in trimester-specific effects to the fetus [2][3][4][5][6][7]. Established animal models of ZIKV infection during pregnancy that result in vertical transmission include non-human primates (NHP) and type-1 interferon/interferon receptor deficient mice. In NHP models, first trimester infection most frequently results in fetal demise and reduced fetal development even in asymptomatic mothers, while second trimester infections tend to produce fetuses with higher viral loads but greater fetal viability [8][9][10]. In all NHP models, fetal pathology ranges from mild to severe manifestations, consistent with Congenital Zika Syndrome (CZS) seen in humans [11][12][13][14][15][16]. While NHP models of ZIKV infection during pregnancy recapitulate human infection, other outbred host models can serve as surrogates when ethical and economic constraints create obstacles to the use of NHP.Sheep offer a unique animal model for translational biomedical research, and have long been used as a model for human pregnancy and fetal development due to longer gestation and comparably staged rates of fetal d...

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mentioning

confidence: 89%

Experimental Infection of Mid-Gestation Pregnant Female and Intact Male Sheep with Zika Virus

Schwarz

Oliveira

Bonfante

et al. 2020

Viruses

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“…The non-human primate (NHP) model of ZIKV infection in pregnancy shares greater similarities with humans than mice [ 61 , 62 ]. NHPs have comparable placental architecture to humans and longer gestation times (macaques, 146–186 days) than rodents and ruminants [ 63 , 64 ] and have been used extensively to study the infection and treatment of other TORCH (Toxoplasmosis, Other [syphilis, varicella-zoster, HIV, parvovirus B19], Rubella, Cytomegalovirus (CMV), and Herpesvirus infections) pathogens [ 65 , 66 , 67 , 68 , 69 ]. Among NHPs, macaques ( Macaca ) have been used most frequently for the study of ZIKV pathogenesis during pregnancy ( Table 2 ).…”

Section: Non-human Primate (Nhp) Modelsmentioning

confidence: 99%

Animal Models of Zika Virus Infection during Pregnancy

Caine

Jagger

Diamond

2018

Viruses

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Zika virus (ZIKV) emerged suddenly in the Americas in 2015 and was associated with a widespread outbreak of microcephaly and other severe congenital abnormalities in infants born to mothers infected during pregnancy. Vertical transmission of ZIKV in humans was confirmed when viral RNA was detected in fetal and placental tissues, and this outcome has been recapitulated experimentally in animals. Unlike other flaviviruses, ZIKV is both arthropod- and sexually-transmitted, and has a broad tissue tropism in humans, including multiple tissues of the reproductive tract. The threats posed by ZIKV have prompted the development of multiple in vivo models to better understand the pathogenesis of ZIKV, particularly during pregnancy. Here, we review the progress on animal models of ZIKV infection during pregnancy. These studies have generated a foundation of insights into the biology of ZIKV, and provide a means for evaluating vaccines and therapeutics.

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“…During this outbreak, the virus was for the first time associated with microcephaly in newborns and Guillain–Barré syndrome in adults. The outbreak triggered the development of several rodent and nonhuman primate models, which already have proven their value by contributing significantly to the understanding of ZIKV-mediated neuropathology 3 – 5 .…”

Section: Introductionmentioning

confidence: 99%

Microencephaly in fetal piglets following in utero inoculation of Zika virus

Schreur

Keulen

Anjema

et al. 2018

Emerging Microbes & Infections

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Zika virus (ZIKV) is a mosquito-borne flavivirus that became associated with microcephaly in newborns and Guillain–Barré syndrome in adults after its emergence in the Pacific and the Americas in 2015. Newly developed rodent and nonhuman primate models have already revealed important insights into ZIKV-induced neuropathology. Nonhuman primates are phylogenetically closely related to humans and are therefore preferred human surrogates in ZIKV research. However, the use of nonhuman primates, particularly during gestation, raises ethical issues. Considering that pigs also share many anatomical and physiological features with humans, this species may be an attractive alternative human surrogate for ZIKV research. Here, we inoculated 20 porcine fetuses in utero and assessed the effect of ZIKV on brain development 4 weeks later. All inoculated fetuses presented mild to severe neuropathology, characterized by a depletion of neurons in the cerebral cortex. In most cases, neuronal depletion was confined to specific cerebral lobes without affecting brain size, whereas in severe cases a more generalized depletion resulted in microencephaly. Although the virus was widespread in the sows’ placenta at the time of necropsy only low levels of viral RNA were detected in fetal brain samples, thereby preventing the identification of primary target cells. Our findings suggest that pigs can be used to study ZIKV-induced neurodevelopmental defects as currently observed in human neonates, varying from stunted brain growth to localized cortical neuronal depletion in the absence of major macroscopic abnormalities.

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Macaque monkeys in Zika virus research: 1947–present

Cited by 35 publications

References 83 publications

Experimental Infection of Mid-Gestation Pregnant Female and Intact Male Sheep with Zika Virus

Experimental Infection of Mid-Gestation Pregnant Female and Intact Male Sheep with Zika Virus

Animal Models of Zika Virus Infection during Pregnancy

Microencephaly in fetal piglets following in utero inoculation of Zika virus

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