scholarly journals Mapping the evolutionary landscape of Zika virus infection in immunocompromised mice

2019 ◽  
Author(s):  
Maria G. Noval ◽  
Margarita V. Rangel ◽  
Katherine E. Johnson ◽  
Elfie De Jesus ◽  
Adam Gerber ◽  
...  
Keyword(s):  
Zika Virus ◽  
Viral Genome ◽  
Transmission Model ◽  
Viral Diversity ◽  
Transmission Route ◽  
Zikv Infection ◽  
Adaptive Process ◽  
Specific Organ ◽  
Vector Borne ◽  
Immunocompromised Mice

AbstractThe fundamental basis of how arboviruses evolve in nature and what regulates the adaptive process remain unclear. To address this problem, we established a Zika virus (ZIKV) vector-borne transmission system in immunocompromised mice that mimics evolutionary characteristics of ZIKV infection in humans. Using this system, we defined factors that influence the evolutionary landscape of ZIKV infection and show that transmission route and specific organ microenvironments impact viral diversity and defective viral genome (DVG) production. In addition, we identified in mice the emergence of ZIKV mutants previously seen in natural infections, including variants present in currently circulating strains, as well as mutations unique to the mouse infections. With these studies, we have established an insect-to-mouse transmission model to study ZIKV evolution. We also defined how organ microenvironments and infection route impact the ZIKV evolutionary landscape, providing a deeper understanding of the factors that regulate arbovirus evolution and emergence.

scholarly journals Mapping the evolutionary landscape of Zika virus infection in immunocompromised mice

2020 ◽  
Vol 6 (2) ◽  
Author(s):  
Katherine E E Johnson ◽  
Maria G Noval ◽  
Margarita V Rangel ◽  
Elfie De Jesus ◽  
Adam Geber ◽  
...  
Keyword(s):  
Zika Virus ◽  
Viral Genome ◽  
Transmission Model ◽  
Transmission Route ◽  
Zikv Infection ◽  
Adaptive Process ◽  
Specific Organ ◽  
Vector Borne ◽  
Immunocompromised Mice

Abstract The fundamental basis of how arboviruses evolve in nature and what regulates the adaptive process remain unclear. To address this problem, we established a Zika virus (ZIKV) vector-borne transmission system in immunocompromised mice to study the evolutionary characteristics of ZIKV infection. Using this system, we defined factors that influence the evolutionary landscape of ZIKV infection and show that transmission route and specific organ microenvironments impact viral diversity and defective viral genome production. In addition, we identified in mice the emergence of ZIKV mutants previously seen in natural infections, including variants present in currently circulating Asian and American strains, as well as mutations unique to the mouse infections. With these studies, we have established an insect-to-mouse transmission model to study ZIKV evolution in vivo. We also defined how organ microenvironments and infection route impact the ZIKV evolutionary landscape, providing a deeper understanding of the factors that regulate arbovirus evolution and emergence.

scholarly journals Zika viruses of both African and Asian lineages cause fetal harm in a vertical transmission model

2018 ◽  
Author(s):  
Anna S. Jaeger ◽  
Reyes A. Murreita ◽  
Lea R. Goren ◽  
Chelsea M. Crooks ◽  
Ryan V. Moriarty ◽  
...  
Keyword(s):  
Mouse Model ◽  
Vertical Transmission ◽  
Birth Defects ◽  
Asian American ◽  
Zika Virus ◽  
French Polynesia ◽  
Transmission Model ◽  
Foreseeable Future ◽  
Zikv Infection ◽  
Congenital Zika Syndrome

AbstractCongenital Zika virus (ZIKV) infection was first linked to birth defects during the American outbreak 1–3. It has been proposed that mutations unique to the Asian/American-genotype explain, at least in part, the ability of Asian/American ZIKV to cause congenital Zika syndrome (CZS) 4,5. Recent studies identified mutations in ZIKV infecting humans that arose coincident with the outbreak in French Polynesia and were stably maintained during subsequent spread to the Americas 5. Here we show that African ZIKV can infect and harm fetuses and that the S139N mutation that has been associated with the American outbreak is not essential for fetal harm. Our findings, in a vertical transmission mouse model, suggest that ZIKV will remain a threat to pregnant women for the foreseeable future, including in Africa, southeast Asia, and the Americas. Additional research is needed to better understand the risks associated with ZIKV infection during pregnancy, both in areas where the virus is newly endemic and where it has been circulating for decades.

scholarly journals Zika Virus-Immune Plasmas from Symptomatic and Asymptomatic Individuals Enhance Zika Pathogenesis in Adult and Pregnant Mice

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Byoung-Shik Shim ◽  
Young-Chan Kwon ◽  
Michael J. Ricciardi ◽  
Mars Stone ◽  
Yuka Otsuka ◽  
...  
Keyword(s):  
Zika Virus ◽  
Passive Immunization ◽  
The Body ◽  
Transmission Model ◽  
Plasma Samples ◽  
Zikv Infection ◽  
Fetal Demise ◽  
Antibody Dependent Enhancement ◽  
Pregnant Mice ◽  
Asymptomatic Individuals

ABSTRACT Preexisting immunity against dengue virus or West Nile virus was previously reported to mediate antibody-dependent enhancement (ADE) of Zika virus (ZIKV) infection in a mouse model. We show here that ZIKV-immune plasma samples from both symptomatic and asymptomatic individuals mediated ZIKV ADE of infection in vitro and in mice. In a lethal infection model with a viral inoculum 10 times higher, both ADE and protection were observed, depending on the amount of infused immune plasma. In a vertical-transmission model, ZIKV-immune plasma infused to timed pregnant mice increased fetal demise and decreased the body weight of surviving fetuses. Depletion of IgG from an immune plasma abolished ADE of infection, and the presence of purified IgG alone mediated ADE of infection. Higher viral loads and proinflammatory cytokines were detected in mice treated with ZIKV-immune plasma samples compared to those receiving control plasma. Together, these data show that passive immunization with homotypic ZIKV antibodies, depending on the concentration, could either worsen or limit a subsequent ZIKV infection. IMPORTANCE Antibody-dependent enhancement (ADE) of virus infection is common to many viruses and is problematic when plasma antibody levels decline to subneutralizing concentrations. ADE of infection is especially important among flaviviruses, many of which are the cause of global health problems. Recently, human plasma samples immune to heterologous flaviviruses were shown to promote Zika virus (ZIKV) infection. Here we showed in immunocompromised mouse models that homologous immune plasma samples protect mice from subsequent infection at high antibody concentrations but that they mediate ADE of infection and increase ZIKV pathogenesis in adult mice and fetal demise during pregnancy at low concentrations.

scholarly journals Zika Virus Production Is Resistant to RNase L Antiviral Activity

2019 ◽  
Vol 93 (16) ◽  
Author(s):  
Jillian N. Whelan ◽  
Yize Li ◽  
Robert H. Silverman ◽  
Susan R. Weiss
Keyword(s):  
Antiviral Activity ◽  
Zika Virus ◽  
Viral Genome ◽  
Molecular Mechanisms ◽  
Virus Production ◽  
Type I ◽  
Rnase L ◽  
Oligoadenylate Synthetase ◽  
Zikv Infection ◽  
Initial Report

SUMMARYThere is currently no knowledge of how the emerging human pathogen Zika virus (ZIKV) interacts with the antiviral endoribonuclease L (RNase L) pathway during infection. Since activation of RNase L during infection typically limits virus production dramatically, we used CRISPR-Cas9 gene editing technology to knockout (KO) targeted host genes involved in the RNase L pathway to evaluate the effects of RNase L on ZIKV infection in human A549 cells. RNase L was activated in response to ZIKV infection, which degraded ZIKV genomic RNA. Surprisingly, despite viral genome reduction, RNase L activity did not reduce ZIKV infectious titers. In contrast, both the flavivirus dengue virus and the alphavirus Sindbis virus replicated to significantly higher titers in RNase L KO cells compared to wild-type (WT) cells. Using MAVS/RNase L double KO cells, we demonstrated that the absence of increased ZIKV production in RNase L KO cells was not due to compensation by enhanced type I interferon transcripts to thus inhibit virus production. Finally, when synthetic double-stranded RNA was detected by OAS3 to induce RNase L antiviral activity prior to ZIKV infection, we observed reduced ZIKV replication factory formation, as well as a 42-fold reduction in virus yield in WT but not RNase L KO cells. This study proposes that ZIKV evades RNase L antiviral activity by generating a viral genome reservoir protected from RNase L cleavage during early infection, allowing for sufficient virus production before RNase L activation is detectable.IMPORTANCEWith the onset of the 2015 ZIKV outbreak, ZIKV pathogenesis has been of extreme global public health interest, and a better understanding of interactions with the host would provide insight into molecular mechanisms driving the severe neurological outcomes of ZIKV disease. Here is the initial report on the relationship between ZIKV and the host oligoadenylate synthetase-RNase L (OAS-RNase L) system, a potent antiviral pathway effective at restricting replication of diverse viruses. Our study elucidated a unique mechanism whereby ZIKV production is impervious to antiviral RNase L activity, through a mechanism of viral RNA protection that is not mimicked during infection with numerous other RNase L-activating viruses, thus identifying a distinct replication strategy potentially important for ZIKV pathogenesis.

scholarly journals Zika Virus Infection in Tourists Travelling to Thailand: Case Series Report

2020 ◽  
Vol 6 (1) ◽  
pp. 3
Author(s):  
Natàlia Romaní ◽  
Marie Antoinette Frick ◽  
Elena Sulleiro ◽  
Carlota Rodó ◽  
María Espiau ◽  
...  
Keyword(s):  
Zika Virus ◽  
Clinical Signs ◽  
Case Series ◽  
World Health ◽  
Prenatally Exposed ◽  
Zikv Infection ◽  
Case Series Report ◽  
Vector Borne ◽  
Health Organization ◽  
Health Care Monitoring

Thailand is a popular tourist destination where Zika virus (ZIKV) transmission is currently active. To our knowledge, there are no reports of ZIKV infection imported from Thailand and affecting children. Here, we describe the clinical and microbiological findings in three cases of vector-borne ZIKV infection: An 11-year-old boy, a 2-year-old girl, and her pregnant mother, this last case leading to the prenatal exposure of her second baby to ZIKV in the second trimester of pregnancy. All patients were diagnosed after traveling to Thailand between September 2019 and January 2020. No complications were detected in any patient at follow-up, and the prenatally exposed fetus showed no abnormalities during intensive antenatal health care monitoring. On postnatal study, there were no clinical signs or microbiological findings of mother-to-child ZIKV transmission. ZIKV IgG was initially positive, but seroreversion occurred at 4 months of life. This report describes the clinical and serological evolution of vector-borne ZIKV infection occurring in dengue-naïve tourists returning from Thailand. The World Health Organization currently recommends that pre-travel advice to prevent arbovirus infection should be maintained in travelers to Southeast Asia.

scholarly journals Surveillance of Zika virus infection in the EU/EEA, June 2015 to January 2017

2017 ◽  
Vol 22 (41) ◽  
Author(s):  
G Spiteri ◽  
B Sudre ◽  
A Septfons ◽  
J Beauté ◽  
Keyword(s):  
Zika Virus ◽  
European Economic Area ◽  
The European Union ◽  
Zikv Infection ◽  
Large Outbreak ◽  
Imported Cases ◽  
Efficient Vector ◽  
Vector Borne ◽  
Almost All ◽  
The Eu

Surveillance of Zika virus (ZIKV) infection in the European Union/European Economic Area (EU/EEA) was implemented in 2016 in response to the large outbreak reported in the Americas in 2015 associated with an increased number of infants born with microcephaly. Between June 2015 and January 2017, 21 EU/EEA countries reported 2,133 confirmed cases of ZIKV infection, of whom 106 were pregnant women. Cases infected in the Caribbean constituted 71% of reported cases. Almost all cases (99%) were most probably infected by mosquito bite during travel outside continental Europe, while only 1% were transmitted sexually. Considering that 584 imported cases were reported between May and October 2016 among residents of areas with established presence of Aedes albopictus, the absence of autochthonous vector-borne cases suggests that Ae. albopictus is not an efficient vector for ZIKV infection.

scholarly journals Persistent detection of Zika virus RNA in semen for six months after symptom onset in a traveller returning from Haiti to Italy, February 2016

2016 ◽  
Vol 21 (32) ◽  
Author(s):  
Emanuele Nicastri ◽  
Concetta Castilletti ◽  
Giuseppina Liuzzi ◽  
Marco Iannetta ◽  
Maria R Capobianchi ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Zika Virus ◽  
Sexual Transmission ◽  
Erythematous Rash ◽  
Zikv Infection ◽  
Virus Rna ◽  
History Of ◽  
Vector Borne

A man in his early 30s reported in January 2016 a history of fever, asthenia and erythematous rash during a stay in Haiti. On his return to Italy, ZIKV RNA was detected in his urine and saliva 91 days after symptom onset, and in his semen on day 188, six months after symptom onset. Our findings support the possibility of sexual transmission of ZIKV and highlight the importance of continuing to investigate non-vector-borne ZIKV infection.

scholarly journals Zika virus and temperature modulate Elizabethkingia anophelis in Aedes albopictus

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Maria G. Onyango ◽  
Rachel Lange ◽  
Sean Bialosuknia ◽  
Anne Payne ◽  
Nicholas Mathias ◽  
...  
Keyword(s):  
Aedes Albopictus ◽  
Negative Correlation ◽  
Blood Meal ◽  
Zika Virus ◽  
Vero Cells ◽  
Zikv Infection ◽  
Viral Loads ◽  
Vector Borne ◽  
Basal Immunity ◽  
Diurnal Temperatures

Abstract Background Vector-borne pathogens must survive and replicate in the hostile environment of an insect’s midgut before successful dissemination. Midgut microbiota interfere with pathogen infection by activating the basal immunity of the mosquito and by synthesizing pathogen-inhibitory metabolites. Methods The goal of this study was to assess the influence of Zika virus (ZIKV) infection and increased temperature on Aedes albopictus midgut microbiota. Aedes albopictus were reared at diurnal temperatures of day 28 °C/night 24 °C (L) or day 30 °C/night 26 °C (M). The mosquitoes were given infectious blood meals with 2.0 × 108 PFU/ml ZIKV, and 16S rRNA sequencing was performed on midguts at 7 days post-infectious blood meal exposure. Results Our findings demonstrate that Elizabethkingia anophelis albopictus was associated with Ae. albopictus midguts exposed to ZIKV infectious blood meal. We observed a negative correlation between ZIKV and E. anophelis albopictus in the midguts of Ae. albopictus. Supplemental feeding of Ae. albopictus with E. anophelis aegypti and ZIKV resulted in reduced ZIKV infection rates. Reduced viral loads were detected in Vero cells that were sequentially infected with E. anophelis aegypti and ZIKV, dengue virus (DENV), or chikungunya virus (CHIKV). Conclusions Our findings demonstrate the influence of ZIKV infection and temperature on the Ae. albopictus microbiome along with a negative correlation between ZIKV and E. anophelis albopictus. Our results have important implications for controlling vector-borne pathogens. Graphical Abstract

scholarly journals Global dynamics analysis of a Zika transmission model with environment transmission route and spatial heterogeneity

2021 ◽  
Vol 7 (3) ◽  
pp. 4803-4832
Author(s):  
Liping Wang ◽  
◽  
Peng Wu ◽  
Mingshan Li ◽  
Lei Shi ◽  
...  
Keyword(s):  
Zika Virus ◽  
Health Agency ◽  
Experimental Result ◽  
Transmission Model ◽  
Uniform Persistence ◽  
Global Dynamics ◽  
Transmission Route ◽  
Global Public Health ◽  
Globally Attractive ◽  
Disease Free

<abstract><p>Zika virus, a recurring mosquito-borne flavivirus, became a global public health agency in 2016. It is mainly transmitted through mosquito bites. Recently, experimental result demonstrated that $ Aedes $ mosquitoes can acquire and transmit Zika virus by breeding in contaminated aquatic environments. The environmental transmission route is unprecedented discovery for the Zika virus. Therefore, it is necessary to introduce environment transmission route into Zika model. Furthermore, we consider diffusive terms in order to capture the movement of humans and mosquitoes. In this paper, we propose a novel reaction-diffusion Zika model with environment transmission route in a spatial heterogeneous environment, which is different from all Zika models mentioned earlier. We introduce the basic offspring number $ R_{0}^{m} $ and basic reproduction number $ R_{0} $ for this spatial model. By using comparison arguments and the theory of uniform persistence, we prove that disease free equilibrium with the absence of mosquitoes is globally attractive when $ R_{0}^{m} &lt; 1 $, disease free equilibrium with the presence of mosquitoes is globally attractive when $ R_{0}^{m} &gt; 1 $ and $ R_{0} &lt; 1 $, the model is uniformly persistent when $ R_{0}^{m} &gt; 1 $ and $ R_{0} &gt; 1 $. Finally, numerical simulations conform these analytical results.</p></abstract>

scholarly journals Gut microbiota modulation induced by Zika virus infection in immunocompetent mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rafael Corrêa ◽  
Igor de Oliveira Santos ◽  
Heloísa Antoniella Braz-de-Melo ◽  
Lívia Pimentel de Sant’Ana ◽  
Raquel das Neves Almeida ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Zika Virus ◽  
Hypervariable Region ◽  
Microbiota Composition ◽  
Colon Tissue ◽  
Zikv Infection ◽  
Immunological Responses ◽  
Immunocompetent Mice ◽  
Gut Microbiota Composition

AbstractGut microbiota composition can modulate neuroendocrine function, inflammation, and cellular and immunological responses against different pathogens, including viruses. Zika virus (ZIKV) can infect adult immunocompetent individuals and trigger brain damage and antiviral responses. However, it is not known whether ZIKV infection could impact the gut microbiome from adult immunocompetent mice. Here, we investigated modifications induced by ZIKV infection in the gut microbiome of immunocompetent C57BL/6J mice. Adult C57BL/6J mice were infected with ZIKV and the gut microbiota composition was analyzed by next-generation sequencing of the V4 hypervariable region present in the bacterial 16S rDNA gene. Our data showed that ZIKV infection triggered a significant decrease in the bacteria belonging to Actinobacteria and Firmicutes phyla, and increased Deferribacteres and Spirochaetes phyla components compared to uninfected mice. Interestingly, ZIKV infection triggered a significant increase in the abundance of bacteria from the Spirochaetaceae family in the gut microbiota. Lastly, we demonstrated that modulation of microbiota induced by ZIKV infection may lead to intestinal epithelium damage and intense leukocyte recruitment to the intestinal mucosa. Taken together, our data demonstrate that ZIKV infection can impact the gut microbiota composition and colon tissue homeostasis in adult immunocompetent mice.

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