Evaluating risks of ZIKV co-infection in SIV-infected macaques
评估感染 SIV 的猕猴中 ZIKV 合并感染的风险
基本信息
- 批准号:10007675
- 负责人:
- 金额:$ 13.92万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-04-01 至 2023-03-31
- 项目状态:已结题
- 来源:
- 关键词:AIDS/HIV problemAcquired Immunodeficiency SyndromeAcuteAdultAnimal ModelAnimalsAntiviral AgentsAreaAutopsyBloodCellsChildClinicalCongenital neurologic anomaliesDengueDengue InfectionDiseaseDisease OutbreaksDisease ProgressionDrug or chemical Tissue DistributionFCGR3B geneFemaleFlavivirusFlavivirus InfectionsFlow CytometryFrequenciesGeographyGoalsHIVHIV InfectionsHistopathologyHumanImmuneImmune responseImmunocompromised HostIn VitroIndividualInfantInfectionInflammationInflammatoryKnowledgeMacacaMacaca nemestrinaMeasurementMeasuresMediatingMentorsModelingMonitorNatural HistoryNeuraxisOutcomePathogenesisPathologyPatientsPeripheral Blood Mononuclear CellPersonsPhenotypePopulationPredispositionPregnancyPregnant WomenPrimatesReportingResearchResourcesRiskRouteSIVSamplingSurveillance MethodsTestingTissuesTrainingUniversitiesVertical Disease TransmissionViralViral Load resultViral PathogenesisVirus ReplicationWashingtonWest Nile virusWomanWorkYellow fever virusZIKV infectionZika Virusadaptive immune responseantiretroviral therapycellular targetingco-infectioncongenital zika syndromecytokineglobal healthhuman diseasein vivoinsightmonocytenervous system disorderneuropathologynonhuman primateprogramsvirology
项目摘要
PROJECT SUMMARY
Over 36 million people are living with HIV and there is large geographic overlap for areas endemic with flavivirus
infection. Despite the occurrence of large flavivirus outbreaks, there is a severe lack of knowledge regarding the
impact flavivirus infections may have on people living with HIV (PLWH). It is unclear what effect HIV co-infection
has on the clinical consequences of flavivirus infection and current studies in humans are limited by low patient
numbers and inconsistent incorporation of HIV disease status into interpretations of flavivirus disease. Non-
human (NHP) models of Zika virus (ZIKV) infection recapitulate several aspects of human disease and are ideal
for evaluating the impact of human flavivirus infection in people living with HIV. However, no established HIV-
ZIKV co-infection animal model exists. In this proposal, we will study the natural history of HIV co-infection with
flaviviruses to understand the risks, causes, and clinical outcomes in PLWH. Previously in NHPs, we showed
that CD16+ monocytes are the major in vivo blood targets of ZIKV and similar results have been found in humans.
Monocyte frequencies increase during HIV infection and although ART reduces total frequencies in HIV infected
persons, CD16+ monocytes remain elevated. We will investigate the hypothesis that HIV infection promotes
susceptibility to flavivirus infection by decreasing anti-viral innate and adaptive immune responses, increasing
inflammation, and expanding cellular targets of infection, including monocytes. HIV invasion of the central
nervous system (CNS) is mediated by CD16+ monocytes, therefore monocytes could also act to spread ZIKV to
the CNS and promote neurological disease. Thus, HIV infection could promote ZIKV pathogenesis and
neuroinvasion by expanding the cellular target pool and inducing inflammation. Additionally, we hypothesize that
enhanced ZIKV pathogenesis occurs in PLWH, and we will experimentally test this using an NHP model of SIV
infection. Specifically, in Aim 1 we will evaluate whether cells from SIV infected animals support greater ZIKV
replication. In Aim 2 we will determine whether ZIKV pathogenesis is enhanced in SIV-infected macaques. We
will determine whether SIV infection promotes invasion of ZIKV into the CNS and determine the innate and
adaptive immune responses corresponding to enhanced infection. These studies will provide significant insights
into the potential risk of enhanced ZIKV pathogenesis in the HIV population and determine if PLWH have a
greater risk of ZIKV-associated pathologies. The goal of this K01 is to support the transition of developing my
own independent research program focused on understanding the impact of viral co-infections in PLWH. In order
to achieve this goal I will expand upon my previous training using NHP models of HIV and ZIKV human infection,
will leverage the resources at the University of Washington and the Washington National Primate Research
Center, and will work closely with my mentors, Dr. Deborah Fuller and Dr. Michael Gale.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Megan A O'Connor其他文献
Megan A O'Connor的其他文献
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{{ truncateString('Megan A O'Connor', 18)}}的其他基金
Mechanisms of SARS-CoV-2 pathogenesis during HIV/SIV infection
HIV/SIV 感染期间 SARS-CoV-2 的发病机制
- 批准号:
10685195 - 财政年份:2023
- 资助金额:
$ 13.92万 - 项目类别:
SARS-CoV-2 vaccine durability during SIV infection
SIV 感染期间 SARS-CoV-2 疫苗的耐久性
- 批准号:
10618112 - 财政年份:2023
- 资助金额:
$ 13.92万 - 项目类别:
Evaluating risks of ZIKV co-infection in SIV-infected macaques
评估感染 SIV 的猕猴中 ZIKV 合并感染的风险
- 批准号:
10397539 - 财政年份:2020
- 资助金额:
$ 13.92万 - 项目类别:
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