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Transcript
In the Name of God Immunopathogenesis of Zika Virus Infection Presented by: F Noorbakhsh, MD PhD, Department of Immunology, School of Medicine, TUMS, Spring 2016 F Noorbakhsh, Dept Immunol, TUMS ZIKV Cell targets Cell surface receptors Innate and adaptive responses Fetal CNS injury After initial inoculation of the virus three groups of cells are targeted by ZIKV Keratinocytes Fibroblasts DC DC Dendritic cells DC Primary human fibroblasts are susceptible to ZIKV Hamel, Misse et al, J Virol 2015 Human Keratinocytes are also susceptible to ZIKV Hamel, Misse et al, J Virol 2015 Human dendritic cells are permissive to ZIKV Hamel, Misse et al, J Virol 2015 Cell surface receptors for ZIKV? Potential candidates: DC-SIGN, TIM1, TIM4, AXL, Tyro3 Different receptors are involved in ZIKV cell entry Immune response against ZIKV? DC DC Innate cytokines (Interferons) T cell cytokines Pattern recognition receptors (PRRs) Chemokines ZIKV induces an innate immune response in human fibroblasts Hamel, Misse et al, J Virol 2015 ZIKV induces the expression of PRRs Hamel, Misse et al, J Virol 2015 TIM1 AXL MDA5 RIG-I TLR3 IFNα, IFNβ CD4 CD4 DC CD4 CD4 CD4 Th2 Th17 Th9 Tappe et al, Med Microbiol Immunol, 2015 Viremia Placenta Infection of fibroblasts Infection of DCs and transfer to lymph nodes Maternal viremia Fetal viremia Infected monocytes Mlakar et al, NEJM March 2016 Acute Disseminated Encephalomyelitis (ADEM) Noorbakhsh et al, Neurol Clin, 2008 Infection of fibroblasts Infection of DCs and transfer to lymph nodes Maternal viremia Direct neurovirulence Indirect immune mediated injury Fetal viremia Infected monocytes Questions and Comments