Zika virus infection and microcephaly: spatial analysis and socio-environmental determinants in a region of high Aedes aegypti infestation in the Central-West Region of Brazil

Abstract Background More than 5 years after the Zika virus (ZIKV) epidemic, Zika infection remains a major concern in regions with high Aedes infestation. The objectives of this study were (i) to identify clusters of ZIKV infection and microcephaly, and/or central nervous system (CNS) alterations associated with congenital infection during the epidemic peak in 2016 and subsequently, in 2017 and 2018; (ii) to measure the non-spatial correlation between ZIKV infection and microcephaly and/or CNS alterations associated with congenital infection; and (iii) to analyse the sociodemographic/economic, health, and environmental determinants associated with the incidence of ZIKV in a region of high infestation by Aedes aegypti in the Central-West Region of Brazil. Methods This ecological study analysed 246 municipalities in the state of Goiás (6.9 million inhabitants). The data were obtained from the Information System for Notifiable Diseases (ZIKV cases) and the Public Health Event Registry (microcephaly and/or CNS alterations associated with congenital infection). Incidence rates and prevalence of ZIKA infection were smoothed by an empirical Bayesian estimator (LEbayes), producing the local empirical Bayesian rate (LEBR). In the spatial analysis, ZIKV infection and microcephaly cases were georeferenced by the municipality of residence for 2016 and grouped for 2017 and 2018. Global Moran's I and the Hot Spot Analysis tool (Getis-Ord Gi* statistics) were used to analyse the spatial autocorrelation and clusters of ZIKV infection and microcephaly, respectively. A generalised linear model from the Poisson family was used to assess the association between ecological determinants and the smoothing incidence rate of ZIKV infection. Results A total of 9892 cases of acute ZIKV infection and 121 cases of microcephaly were confirmed. The mean LEBR of the ZIKV infection in the 246 municipalities was 22.3 cases/100,000 inhabitants in 2016, and 10.3 cases/100,000 inhabitants in 2017 and 2018. The LEBR of the prevalence rate of microcephaly and/or CNS alterations associated with congenital infection was 7 cases/10,000 live births in 2016 and 2 cases/10,000 live births during 2017–2018. Hotspots of ZIKV infection and microcephaly cases were identified in the capital and neighbouring municipalities in 2016, with new clusters in the following years. In a multiple regression Poisson analysis, ZIKV infection was associated with higher population density, the incidence of dengue, Aedes larvae infestation index, and average rainfall. The important determinant of ZIKV infection incidence reduction was the increase in households attended by endemic disease control agents. Conclusions Our analyses were able to capture, in a more granular way, aspects that make it possible to inform public managers of the sentinel areas identified in the post-epidemic hotspots.

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Analysis of Zika virus capsid-Aedes aegypti mosquito interactome reveals pro-viral host factors critical for establishing infection

Nature Communications ◽

10.1038/s41467-021-22966-8 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Rommel J. Gestuveo ◽

Jamie Royle ◽

Claire L. Donald ◽

Douglas J. Lamont ◽

Edward C. Hutchinson ◽

...

Keyword(s):

Aedes Aegypti ◽

Protein Interactions ◽

Zika Virus ◽

Label Free ◽

Protein Protein Interactions ◽

Zikv Infection ◽

Ubiquitin Protein Ligase ◽

Mosquito Cells ◽

Endoplasmic Reticulum Protein ◽

Arboviral Diseases

AbstractThe escalating global prevalence of arboviral diseases emphasizes the need to improve our understanding of their biology. Research in this area has been hindered by the lack of molecular tools for studying virus-mosquito interactions. Here, we develop an Aedes aegypti cell line which stably expresses Zika virus (ZIKV) capsid proteins in order to study virus-vector protein-protein interactions through quantitative label-free proteomics. We identify 157 interactors and show that eight have potentially pro-viral activity during ZIKV infection in mosquito cells. Notably, silencing of transitional endoplasmic reticulum protein TER94 prevents ZIKV capsid degradation and significantly reduces viral replication. Similar results are observed if the TER94 ortholog (VCP) functioning is blocked with inhibitors in human cells. In addition, we show that an E3 ubiquitin-protein ligase, UBR5, mediates the interaction between TER94 and ZIKV capsid. Our study demonstrates a pro-viral function for TER94/VCP during ZIKV infection that is conserved between human and mosquito cells.

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Embryonic Stage of Congenital Zika Virus Infection Determines Fetal and Postnatal Outcomes in Mice

Viruses ◽

10.3390/v13091807 ◽

2021 ◽

Vol 13 (9) ◽

pp. 1807

Author(s):

Eri Nakayama ◽

Yasuhiro Kawai ◽

Satoshi Taniguchi ◽

Jessamine E. Hazlewood ◽

Ken-ichi Shibasaki ◽

...

Keyword(s):

Zika Virus ◽

Neutralizing Antibodies ◽

Neonatal Death ◽

Motor Behavior ◽

Wide Spectrum ◽

Fetal Loss ◽

Congenital Infection ◽

Sensory Function ◽

Zikv Infection ◽

Wide Range

Zika virus (ZIKV) infection during pregnancy causes a wide spectrum of congenital abnormalities and postnatal developmental sequelae such as fetal loss, intrauterine growth restriction (IUGR), microcephaly, or motor and neurodevelopmental disorders. Here, we investigated whether a mouse pregnancy model recapitulated a wide range of symptoms after congenital ZIKV infection, and whether the embryonic age of congenital infection changed the fetal or postnatal outcomes. Infection with ZIKV strain PRVABC59 from embryonic day 6.5 (E6.5) to E8.5, corresponding to the mid-first trimester in humans, caused fetal death, fetal resorption, or severe IUGR, whereas infection from E9.5 to E14.5, corresponding to the late-first to second trimester in humans, caused stillbirth, neonatal death, microcephaly, and postnatal growth deficiency. Furthermore, 4-week-old offspring born to dams infected at E12.5 showed abnormalities in neuropsychiatric state, motor behavior, autonomic function, or reflex and sensory function. Thus, our model recapitulated the multiple symptoms seen in human cases, and the embryonic age of congenital infection was one of the determinant factors of offspring outcomes in mice. Furthermore, maternal neutralizing antibodies protected the offspring from neonatal death after congenital infection at E9.5, suggesting that neonatal death in our model could serve as criteria for screening of vaccine candidates.

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Low Aedes aegypti Vector Competence for Zika Virus from Viremic Rhesus Macaques

Viruses ◽

10.3390/v12121345 ◽

2020 ◽

Vol 12 (12) ◽

pp. 1345

Author(s):

Rosilainy Surubi Fernandes ◽

Mariana Rocha David ◽

Filipe Vieira Santos De Abreu ◽

Anielly Ferreira-de-Brito ◽

Noemi R. Gardinali ◽

...

Keyword(s):

Viral Load ◽

Aedes Aegypti ◽

Short Duration ◽

Zika Virus ◽

Rhesus Macaques ◽

Vector Competence ◽

Transmission Dynamics ◽

Zikv Infection ◽

Transmission Rates ◽

Time Points

Despite worldwide efforts to understand the transmission dynamics of Zika virus (ZIKV), scanty evaluation has been made on the vector competence of Aedes aegypti fed directly on viremic human and non-human primates (NHPs). We blood-fed Ae. aegypti from two districts in Rio de Janeiro on six ZIKV infected pregnant rhesus macaques at several time points, half of which were treated with Sofosbuvir (SOF). Mosquitoes were analyzed for vector competence after 3, 7 and 14 days of incubation. Although viremia extended up to eight days post monkey inoculation, only mosquitoes fed on the day of the peak of viremia, recorded on day two, became infected. The influence of SOF treatment could not be assessed because the drug was administered just after mosquito feeding on day two. The global infection, dissemination and transmission rates were quite low (4.09%, 1.91% and 0.54%, respectively); no mosquito was infected when viremia was below 1.26 × 105 RNA copies/mL. In conclusion, Ae. aegypti vector competence for ZIKV from macaques is low, likely to be due to low viral load and the short duration of ZIKV viremia in primates suitable for infecting susceptible mosquitoes. If ZIKV infection in human and macaques behaves similarly, transmission of the Zika virus in nature is most strongly affected by vector density.

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Prevalence of individual brain and eye defects potentially related to Zika virus in pregnancy in 22 U.S. states and territories, January 2016 - June 2017

10.21203/rs.3.rs-1189990/v1 ◽

2022 ◽

Author(s):

Augustina Delaney ◽

Samantha M. Olson ◽

Nicole M. Roth ◽

Janet D. Cragan ◽

Shana Godfred-Cato ◽

...

Keyword(s):

Birth Defects ◽

Zika Virus ◽

Cortical Atrophy ◽

Zikv Infection ◽

Live Births ◽

Prevalence Estimates ◽

Surveillance Programs ◽

Prevalence Ratios ◽

Cerebral Cortical Atrophy ◽

In Pregnancy

Abstract During the Centers for Disease Control and Prevention’s Zika Virus Response, birth defects surveillance programs adapted to monitor birth defects potentially related to Zika virus (ZIKV) infection during pregnancy. Pregnancy outcomes occurring during January 2016-June 2017 in 22 U.S. states and territories were used to estimate the prevalence of those brain and eye defects potentially related to ZIKV. Jurisdictions were divided into three groups: areas with widespread ZIKV transmission, areas with limited local ZIKV transmission, and areas without local ZIKV transmission. Prevalence estimates for selected brain and eye defects and microcephaly per 10,000 live births were estimated. Prevalence ratios (PRs) and 95% confidence intervals (CIs) were estimated using Poisson regression for areas with widespread and limited ZIKV transmission compared to areas without local ZIKV transmission. Defects with significantly higher prevalence in areas of widespread transmission were pooled, and PRs were calculated by quarter, comparing subsequent quarters to the first quarter (January – March 2016). Nine defects had significantly higher prevalence in areas of widespread transmission. The highest PRs were seen in intracranial calcifications (PR=12.6, 95% CI [7.4, 21.3]), chorioretinal abnormalities (12.5 [7.1, 22.3]), brainstem abnormalities (9.3, [4.7, 18.4]), and cerebral/cortical atrophy (6.7, [4.2, 10.8]). The PR of the nine pooled defects was significantly higher in three quarters in areas with widespread transmission. The largest difference in prevalence was observed for defects consistently reported in infants with congenital ZIKV infection. Birth defects surveillance programs could consider monitoring a subset of birth defects potentially related to ZIKV in pregnancy.

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Coupled small molecules target RNA interference and JAK/STAT signaling to reduce Zika virus infection in Aedes aegypti

10.1101/2021.08.23.457417 ◽

2021 ◽

Author(s):

Chasity E. Trammell ◽

Gabriela Ramirez ◽

Irma Sanchez-Vargas ◽

Shirley Luckhart ◽

Rushika Perera ◽

...

Keyword(s):

Aedes Aegypti ◽

Small Molecules ◽

Insulin Signaling ◽

Zika Virus ◽

Disease Incidence ◽

Virus Transmission ◽

Zikv Infection ◽

Small Molecule Drugs ◽

Pathway Activation ◽

Target Rna

The recent global Zika epidemics have revealed the significant threat that mosquito-borne viruses pose. There are currently no effective vaccines or prophylactics to prevent Zika virus (ZIKV) infection. Limiting exposure to infected mosquitoes is best way to reduce disease incidence. Recent studies have focused on targeting mosquito reproduction and immune responses to reduce transmission. In particular, previous work evaluated the effect of insulin signaling on antiviral JAK/STAT and RNAi in vector mosquitoes. In this work, we demonstrate that targeting insulin signaling through the repurposing of small molecule drugs results in the activation of both of these antiviral pathways. Activation of this coordinated response additively reduced ZIKV levels in Aedes aegypti mosquitoes. This effect included a quantitatively greater reduction in salivary gland ZIKV levels relative to single pathway activation, indicating the potential for field delivery of these small molecules to substantially reduce virus transmission.

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Comprehensive quantitative proteome analysis of Aedes aegypti identifies proteins and pathways involved in Wolbachia pipientis and Zika virus interference phenomenon

10.1101/2020.12.12.422506 ◽

2020 ◽

Author(s):

Michele Martins ◽

Luis Felipe Costa Ramos ◽

Jimmy Rodriguez Murillo ◽

André Torres ◽

Stephanie Serafim de Carvalho ◽

...

Keyword(s):

Mass Spectrometry ◽

Immune Response ◽

Aedes Aegypti ◽

Humoral Immune Response ◽

Zika Virus ◽

Mosquito Vector ◽

Ros Production ◽

Zikv Infection ◽

Wolbachia Pipientis ◽

Humoral Immune

ABSTRACTZika virus is a global public health emergency due to its association with microcephaly, Guillain-Barré syndrome, neuropathy, and myelitis in children and adults. A total of 87 countries have had evidence of autochthonous mosquito-borne transmission of Zika virus, distributed across four continents, and no antivirus therapy or vaccines are available. Therefore, several strategies have been developed to target the main mosquito vector, Aedes aegypti, to reduce the burden of different arboviruses. Among such strategies, the use of the maternally-inherited endosymbiont Wolbachia pipientis has been applied successfully to reduce virus susceptibility and decrease transmission. However, the mechanisms by which Wolbachia orchestrate resistance to ZIKV infection remain to be elucidated. In this study, we apply isobaric labeling quantitative mass spectrometry-based proteomics to quantify proteins and identify pathways altered during ZIKV infection; Wolbachia infection; co-infection with Wolbachia/ZIKV in the Ae. aegypti heads and salivary glands. We show that Wolbachia regulates proteins involved in ROS production, regulates humoral immune response, and antioxidant production. The reduction of ZIKV polyprotein in the presence of Wolbachia in mosquitoes was determined by mass spectrometry and corroborates the idea that Wolbachia helps to block ZIKV infections in Ae. aegypti. The present study offers a rich resource of data that may help to elucidate mechanisms by which Wolbachia orchestrate resistance to ZIKV infection in Ae. aegypti, and represents a step further on the development of new targeted methods to detect and quantify ZIKV and Wolbachia directly in complex tissues.HighlightsThe abundance of ZIKV polyprotein is reduced in the presence of WolbachiaShotgun proteomics quantifies ZIKV and Wolbachia proteins directly in tissuesWolbachia regulates proteins involved in ROS productionWolbachia regulates humoral immune response and antioxidant productionMetabolism and detoxification processes were associated with mono infections

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Reassessment of the risk of birth defects due to Zika virus in Guadeloupe, 2016

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0009048 ◽

2021 ◽

Vol 15 (3) ◽

pp. e0009048

Author(s):

Anna L. Funk ◽

Bruno Hoen ◽

Ingrid Vingdassalom ◽

Catherine Ryan ◽

Philippe Kadhel ◽

...

Keyword(s):

Pregnant Women ◽

Birth Defects ◽

Zika Virus ◽

Prospective Cohort ◽

Trial Registration ◽

Rt Pcr ◽

Zikv Infection ◽

Live Births ◽

Outbreak Period ◽

Neurological Conditions

Background In the French Territories in the Americas (FTA), the risk of birth defects possibly associated with Zika virus (ZIKV) infection was 7.0% (95%CI: 5.0 to 9.5) among foetuses/infants of 546 women with symptomatic RT-PCR confirmed ZIKV infection during pregnancy. Many of these defects were isolated measurement-based microcephaly (i.e. without any detected brain or clinical abnormalities) or mild neurological conditions. We wanted to estimate the proportion of such minor findings among live births of women who were pregnant in the same region during the outbreak period but who were not infected with ZIKV. Methods In Guadeloupe, pregnant women were recruited at the time of delivery and tested for ZIKV infection. The outcomes of live born infants of ZIKV non-infected women were compared to those of ZIKV-exposed live born infants in Guadeloupe, extracted from the FTA prospective cohort. Results Of 490 live born infants without exposure to ZIKV, 42 infants (8.6%, 95%CI: 6.2–11.4) had mild abnormalities that have been described as ‘potentially linked to ZIKV infection’; all but one of these was isolated measurement-based microcephaly. Among the 241 live born infants with ZIKV exposure, the proportion of such abnormalities, using the same definition, was similar (6.6%, 95%CI: 3.8–10.6). Conclusions Isolated anthropometric abnormalities and mild neurological conditions were as prevalent among infants with and without in-utero ZIKV exposure. If such abnormalities had not been considered as ‘potentially linked to ZIKV’ in the original prospective cohort in Guadeloupe, the overall estimate of the risk of birth defects considered due to the virus would have been significantly lower, at approximately 1.6% (95% CI: 0.4–4.1). Trial registration ClinicalTrials.gov (NCT02916732)

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The Extrinsic Incubation Period of Zika Virus in Florida Mosquitoes Aedes aegypti and Ae. albopictus

Pathogens ◽

10.3390/pathogens10101252 ◽

2021 ◽

Vol 10 (10) ◽

pp. 1252

Author(s):

Rebecca A. Zimler ◽

Barry W. Alto

Keyword(s):

Aedes Aegypti ◽

Incubation Period ◽

Health Risks ◽

Zika Virus ◽

Mosquito Vectors ◽

Zikv Infection ◽

Infected Blood ◽

Extrinsic Incubation Period ◽

Asian Lineage ◽

Blood Meals

The Asian genotype of Zika virus (ZIKV) emerged in Brazil in 2015 and subsequently spread throughout the Americas. In July 2016, Florida experienced its first locally acquired ZIKV infection in the continental U.S. Concerns about health risks from ZIKV infection have increased the need to investigate the interactions between potential mosquito vectors and ZIKV. The time it takes for an arbovirus to propagate within a mosquito, and become transmissible, is the extrinsic incubation period (EIP). The EIP for potential mosquito vectors in Florida is unknown. To address this gap in the understanding of ZIKV epidemiology, Florida Aedes aegypti (L.) and Ae. albopictus (Skuse) were orally exposed to ZIKV infected blood meals and fully engorged mosquitoes were held at a constant temperature of 28 °C through the duration of the experiment. Saliva expectorates were collected from cohorts of mosquitoes and tested for the presence of ZIKV at three-day intervals over a period of 24 days to allow for an evaluation of the EIP of the emergent Asian lineage of ZIKV. High rates of infected bodies in Ae. albopictus (75–94%) and Ae. aegypti (68–86%) were observed throughout the incubation period, which did not differ by species. Higher rates of disseminated infection were observed later during the incubation period but did not differ between species. We calculated the 50% EIP to be shorter in Ae. albopictus than Ae. aegypti (16.2 and 18.2 days post infection, respectively). The competence for ZIKV observed in both species may contribute to high rates of ZIKV transmission in Florida populations.

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Global transcriptome analysis of Aedes aegypti mosquitoes in response to Zika virus infection

10.1101/179416 ◽

2017 ◽

Cited By ~ 1

Author(s):

Kayvan Etebari ◽

Shivanand Hegde ◽

Miguel A Saldaña ◽

Steven G Widen ◽

Thomas G Wood ◽

...

Keyword(s):

Virus Infection ◽

Aedes Aegypti ◽

Dengue Virus ◽

Zika Virus ◽

Target Genes ◽

World Health ◽

Mosquito Vector ◽

Zikv Infection ◽

Zika Virus Infection ◽

Non Coding Rnas

AbstractZika virus (ZIKV) of the Flaviviridae family is a recently emerged mosquito-borne virus that has been implicated in the surge of the number of microcephaly instances in South America. The recent rapid spread of the virus led to its declaration as a global health emergency by the World Health Organization. The virus is transmitted mainly by the mosquito Aedes aegypti that also vectors dengue virus, however little is known about the interactions of the virus with the mosquito vector. In this study, we investigated the transcriptome profiles of whole Ae. aegypti mosquitoes in response to ZIKV infection at 2, 7, and 14 days post-infection using RNA-Seq. Results showed changes in the abundance of a large number of transcripts at each time point following infection, with 18 transcripts commonly changed among the three time points. Gene ontology analysis revealed that most of the altered genes are involved in metabolic process, cellular process and proteolysis. In addition, 486 long intergenic non-coding RNAs were identified that were altered upon ZIKV infection. Further, we found correlational changes of a number of potential mRNA target genes with that of altered host microRNAs. The outcomes provide a basic understanding of Ae. aegypti responses to ZIKV and helps to determine host factors involved in replication or mosquito host anti-viral response against the virus.ImportanceVector-borne viruses pose great risks on human health. Zika virus has recently emerged as a global threat, rapidly expanding its distribution. Understanding the interactions of the virus with mosquito vectors at the molecular level is vital for devising new approaches in inhibiting virus transmission. In this study, we embarked on analyzing the transcriptional response of Aedes aegypti mosquitoes to Zika virus infection. Results showed large changes both in coding and long non-coding RNAs. Analysis of these genes showed similarities with other flaviviruses, including dengue virus, which is transmitted by the same mosquito vector. The outcomes provide a global picture of changes in the mosquito vector in response to Zika virus infection.

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Vector competence of Aedes aegypti and Culex quinquefasciatus from the metropolitan area of Guadalajara, Jalisco, Mexico for Zika virus

Scientific Reports ◽

10.1038/s41598-019-53117-1 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Darwin Elizondo-Quiroga ◽

Miriam Ramírez-Medina ◽

Abel Gutiérrez-Ortega ◽

Armando Elizondo-Quiroga ◽

José Esteban Muñoz-Medina ◽

...

Keyword(s):

Aedes Aegypti ◽

Culex Quinquefasciatus ◽

Zika Virus ◽

Vector Competence ◽

Virus Transmission ◽

Blood Feeding ◽

Surveillance Program ◽

Virus Spread ◽

Zikv Infection ◽

Almost All

AbstractZika virus (ZIKV) is a mosquito-borne pathogen discovered in the late 40’s in Uganda during a surveillance program for yellow fever. By 2014 the virus reached Eastern Island in the Americas, and two years later, the virus spread to almost all countries and territories of the Americas. The mosquito Aedes aegypti has been identified as the main vector of the disease, and several researchers have also studied the vector competence of Culex quinquefasciatus in virus transmission. The aim of the present study was to evaluate the vector competence of Ae. aegypti and Cx. quinquefasciatus in order to understand their roles in the transmission of ZIKV in Guadalajara, Jalisco, Mexico. In blood feeding laboratry experiments, we found that Ae. aegypti mosquitoes showed to be a competent vector able to transmit ZIKV in this area. On the other hand, we found that F0 Cx. quinquefasciatus mosquitoes are refractory to ZIKV infection, dissemination and transmission.

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