Download Hamel, Misse et al, J Virol 2015

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