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New insights into innate immune restriction of West Nile virus infection.

ABSTRACT: West Nile virus (WNV) is an encephalitic flavivirus that has provided a valuable experimental system for studying viral pathogenesis and immunity. Although in vitro approaches and mouse models of infection have identified pattern recognition receptor and interferon pathways that control WNV infection, our appreciation of specific antiviral effectors has been more limited. In this review, we highlight recent advances in our understanding of the host factors that restrict WNV infection in mammals and insects, especially those resulting from large-scale screening approaches.

SUBMITTER: Lazear HM

PROVIDER: S-EPMC4456296 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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New insights into innate immune restriction of West Nile virus infection.

Lazear Helen M HM Diamond Michael S MS

Current opinion in virology 20141231

West Nile virus (WNV) is an encephalitic flavivirus that has provided a valuable experimental system for studying viral pathogenesis and immunity. Although in vitro approaches and mouse models of infection have identified pattern recognition receptor and interferon pathways that control WNV infection, our appreciation of specific antiviral effectors has been more limited. In this review, we highlight recent advances in our understanding of the host factors that restrict WNV infection in mammals ...[more]

PMID: 25554924

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Project description:West Nile Virus (WNV) is a flavivirus involved in many human infections worldwide. This arthropod-borne virus is directly co-inoculated with mosquito saliva through the epidermis and the dermis during blood meal. WNV starts replicating in the skin before migrating to the draining lymph node, leading to widespread viremia and in some cases to neurological symptoms. Skin is a complex organ composed of different cell types that together perform essential functions such as pathogen sensing, barrier maintenance and immunity. Keratinocytes, which represent 90% of the cells of the epidermis, are the organism's first line of defense, initiating innate immune response by recognizing pathogens through their pattern recognition receptors. Although WNV was previously known to replicate in human primary keratinocytes, the induced inflammatory response remains unknown. The aim of this study was first to characterize the inflammatory response of human primary keratinocytes to WNV infection and then, to assess the potential role of co-inoculated mosquito saliva on the keratinocyte immune response and viral replication. A type I and III interferon inflammatory response associated with an increase of IRF7 but not IRF3 mRNA expression, and dependent on infectious dose, was observed during keratinocyte infection with WNV. Expression of several interferon-stimulated gene mRNA was also increased at 24 h post-infection (p.i.); they included CXCL10 and interferon-induced proteins with tetratricopeptide repeats (IFIT)-2 sustained up until 48 h p.i. Moreover, WNV infection of keratinocyte resulted in a significant increase of pro-inflammatory cytokines (TNF?, IL-6) and various chemokines (CXCL1, CXCL2, CXCL8 and CCL20) expression. The addition of Aedes aegypti or Culex quinquefasciatus mosquito saliva, two vectors of WNV infection, to infected keratinocytes led to a decrease of inflammatory response at 24 h p.i. However, only Ae. Aegypti saliva adjunction induced modulation of viral replication. In conclusion, this work describes for the first time the inflammatory response of human primary keratinocytes to WNV infection and its modulation in presence of vector mosquito saliva. The effects of mosquito saliva assessed in this work could be involved in the early steps of WNV replication in skin promoting viral spread through the body.

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New insights into innate immune restriction of West Nile virus infection.

Publications

New insights into innate immune restriction of West Nile virus infection.

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