Evasion of the human innate immune system by dengue virus

Pagni, Sarah; Fernández-Sesma, Ana

doi:10.1007/s12026-012-8334-2

Cited by 29 publications

(23 citation statements)

References 62 publications

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“…We observed similar patterns of susceptibility using five different strains of ZIKV, including a contemporary human clinical isolate as well as historical African strains, highlighting the utility of the Ifnar1 −/− mouse model for a range of studies of ZIKV pathogenesis. Although further studies are warranted, the relative resistance of adult mice may reflect an inability of ZIKV to antagonize murine IFN-α/β signaling or effector functions efficiently, analogous to DENV (Pagni and Fernandez-Sesma, 2012; Suthar et al, 2013). The only adult mice we found susceptible to lethal ZIKV infection were Ifnar1 −/− , Irf3 −/− Irf5 −/− Irf7 −/− TKO, and AG129 ( Ifnar1 and Ifngr1 deficient) mice, all of which lack the capacity either to respond to or induce IFN-α/β.…”

Section: Discussionmentioning

confidence: 99%

A Mouse Model of Zika Virus Pathogenesis

Lazear

Govero

Smith

et al. 2016

Cell Host & Microbe

837

955

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SUMMARY Due to the ongoing Zika virus (ZIKV) epidemic and unexpected clinical outcomes including Guillain-Barré syndrome and birth defects, there is an urgent need for animal model development. We evaluated infection and pathogenesis with contemporary and historical ZIKV strains in immunocompetent mice and transgenic mice lacking components of the innate antiviral response. Whereas 4 to 6 week-old wild-type, Irf3−/−, Irf5−/−, and Mavs−/−, mice showed no overt clinical illness, Irf3−/− Irf5−/− Irf7−/− TKO and Ifnar1−/− mice developed neurological disease and succumbed to ZIKV infection. Ifnar1−/− mice sustained high viral loads in the brain and spinal cord, consistent with evidence that ZIKV causes neurodevelopmental defects in human fetuses. The highest viral loads were detected in the testes of Ifnar1−/− mice, which is relevant to sexual transmission of ZIKV. This model of ZIKV pathogenesis will be valuable for evaluating vaccines and therapeutics, as well as understanding basic mechanisms of disease pathogenesis and immune evasion.

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Section: Discussionmentioning

confidence: 99%

A Mouse Model of Zika Virus Pathogenesis

Lazear

Govero

Smith

et al. 2016

Cell Host & Microbe

837

955

View full text Add to dashboard Cite

show abstract

“…128 Gene expression studies of dengue cases of varying severity highlighted differences according to day of illness and revealed shock signatures – DSS cases had reduced interferon-stimulated genes and increased mitochondrial function. 129,130 Another notable observation was that DENV induces CD14 + CD16 + monocytes, which can promote B cell differentiation into plasmablasts and antibody secretion.…”

Section: Immune Correlates Of Protection and Riskmentioning

confidence: 99%

Dengue: knowledge gaps, unmet needs, and research priorities

Katzelnick

Coloma

Harris

2017

The Lancet Infectious Diseases

177

162

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Summary Dengue virus (DENV) is a mosquito-borne pathogen that causes up to ~100 million dengue cases each year, placing a major public health, social and economic burden on numerous low- and middle-income countries (LMICs). Major advances by scientists, vaccine developers, and affected communities are revealing new insights and enabling novel interventions and approaches to dengue prevention and control. Such research has highlighted further questions about both the basic understanding of dengue and efforts to develop new tools. We discuss existing approaches to dengue diagnostics, disease prognosis, surveillance, and vector control in LMICs as well as potential consequences of vaccine introduction. We also summarize current knowledge and recent insights into dengue epidemiology, immunology, and pathogenesis, and their implications for understanding natural infection and current and future vaccines.

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“…Interferons (IFNs) are central players in the innate immune system for defense against pathogen infection. However, DENV harbors a number of virulence proteins that interfere with the IFN signaling pathway [4,44-48]. The NS2A, NS4A, and NS4B proteins contribute to immune invasion by disrupting type I IFN signaling [44,46,47].…”

Section: Reviewmentioning

confidence: 99%

An emerging role for the anti-inflammatory cytokine interleukin-10 in dengue virus infection

et al. 2013

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Infection with dengue virus (DENV) causes both mild dengue fever and severe dengue diseases, such as dengue hemorrhagic fever and dengue shock syndrome. The pathogenic mechanisms for DENV are complicated, involving viral cytotoxicity, immunopathogenesis, autoimmunity, and underlying host diseases. Viral load correlates with disease severity, while the antibody-dependent enhancement of infection largely determines the secondary effects of DENV infection. Epidemiological and experimental studies have revealed an association between the plasma levels of interleukin (IL)-10, which is the master anti-inflammatory cytokine, and disease severity in patients with DENV infection. Based on current knowledge of IL-10-mediated immune regulation during infection, researchers speculate an emerging role for IL-10 in clinical disease prognosis and dengue pathogenesis. However, the regulation of dengue pathogenesis has not been fully elucidated. This review article discusses the regulation and implications of IL-10 in DENV infection. For future strategies against DENV infection, manipulating IL-10 may be an effective antiviral treatment in addition to the development of a safe dengue vaccine.

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Evasion of the human innate immune system by dengue virus

Cited by 29 publications

References 62 publications

A Mouse Model of Zika Virus Pathogenesis

A Mouse Model of Zika Virus Pathogenesis

Dengue: knowledge gaps, unmet needs, and research priorities

An emerging role for the anti-inflammatory cytokine interleukin-10 in dengue virus infection

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