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Genetic evolution, pathogenesis and immune responses in mother to child transmission of ZIKV

ZIKV 母婴传播的遗传进化、发病机制和免疫反应

基本信息

批准号：
9925059
负责人：
GENHONG CHENG
金额：
$ 75.04万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-05-02 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9925059
关键词：
Address Affect African Age-Months American Americas Anatomy Anti-Inflammatory Agents Antibodies Asians Bite Blood CD14 gene Cell physiology Cells Clinical Collaborations Complex Culicidae DNA Sequence Alteration Data Defect Development Disease Disease Outbreaks Epidemic Evolution Exposure to Genetic Genomics Genotype Geography Human Immune Immune response Immune system Immunity Immunoglobulin M Immunologics Immunosuppression Infant Infection Inflammation Joints Lead Life Maternal-Fetal Transmission Measures Mediating Methods Microcephaly Molecular Mothers Mutation Outcome Pathogenesis Pathogenicity Patients Pattern Perinatal Peripheral Placenta Point Mutation Population Pregnancy Pregnancy Outcome Pregnant Women Prospective cohort Publishing RNA Sequences Recurrence Relapse Reporting Research Personnel Rubella Severity of illness Specimen Structural Congenital Anomalies Syndrome Testing Thailand Time Urine Vertical Disease Transmission Viral Viral Genome Viral Load result Viral Pathogenesis Viremia Virus Virus Shedding ZIKV infection Zika Virus adverse outcome adverse pregnancy outcome antenatal base cohort congenital infection cytokine fetal follow-up genetic evolution genomic RNA in utero in vivo infant outcome macrophage monocyte mouse model neonatal infection neurodevelopment neutralizing antibody pregnant prospective response translational study transmission process virology virus genetics

项目摘要

Abstract/Summary Our group of investigators has been collaborating over the last two years to describe the clinical aspects and pathogenesis of in utero transmission of ZIKA virus (ZIKV) infection. We have embarked in a strong collaborative effort to document and understand the pathogenesis of ZIKV. We have available to us a unique prospective cohort of well characterized ZIKV-infected mother-infant pairs who have been followed since the antenatal period, with infants now between 12 to 24 months of age and specimens collected over time. We propose to characterize ZIKV humoral immune responses over time in our cohort of mother-infant pairs who became infected during the Rio de Janeiro 2015/16 epidemic, in order to determine the timing of development of immune responses to ZIKV in perinatally infected infants, and possible correlation with intermittent viral shedding. We plan to evaluate whether infant immune responses are associated with the breadth and potency of maternal immunologic responses to ZIKV over time. To do so we will measure neutralizing antibody activity in 100 mother-infant pairs over 3 years and explore potential associations with annual infant neurodevelopmental assessments and timing of infection in gestation. We will also investigate genetic viral evolution in their ZIKV isolates and are presently sequencing whole ZIKV genome from mother-infant pairs from the same cohort who had adverse pregnancy outcomes, normal pregnancy outcomes, recurrent or relapsing infections, while also checking whether there is variability in viral sequences by compartment (CSF, blood, urine, placenta). We are also evaluating specific ZIKV-immune responses at the cellular and molecular levels and determining mechanisms by which the virus evades host immune responses during pregnancy. Our findings will answer important questions pertaining to the mechanisms of immune pathogenesis and intrinsic virologic factors associated with ZIKV mother-to-child transmission which may be predictive of longer term infant outcomes. Our well characterized population of mother-infant pairs with detailed clinical follow-up and specimens collected over time allows us to perform state of the art translational studies to elucidate mechanisms of viral pathogenesis.

抽象/总结