Innate Immune Control of West Nile Virus Infection

Section of Infectious Diseases, Yale School of Medicine, New Haven, CT, USA.
Cellular Microbiology (Impact Factor: 4.92). 07/2011; 13(11):1648-58. DOI: 10.1111/j.1462-5822.2011.01649.x
Source: PubMed


West Nile virus (WNV), from the Flaviviridae family, is a re-emerging zoonotic pathogen of medical importance. In humans, WNV infection may cause life-threatening meningoencephalitis or long-term neurologic sequelae. WNV is transmitted by Culex spp. mosquitoes and both the arthropod vector and the mammalian host are equipped with antiviral innate immune mechanisms sharing a common phylogeny. As far as the current evidence is able to demonstrate, mosquitoes primarily rely on RNA interference, Toll, Imd and JAK-STAT signalling pathways for limiting viral infection, while mammals are provided with these and other more complex antiviral mechanisms involving antiviral effectors, inflammatory mediators, and cellular responses triggered by highly specialized pathogen detection mechanisms that often resemble their invertebrate ancestry. This mini-review summarizes our current understanding of how the innate immune systems of the vector and the mammalian host react to WNV infection and shape its pathogenesis.

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Available from: Penghua Wang, Oct 06, 2015
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    • "Evidence is also emerging that CLRs recognizing glycosylated flaviviruses may play a role in the infection of vector mosquito species (Arjona et al., 2011; Cheng et al., 2010). "
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    ABSTRACT: Flaviviruses are a group of single-stranded positive sense RNA viruses that generally circulate between arthropod vectors and susceptible vertebrate hosts, producing significant human and veterinary disease burdens. Intensive research efforts have broadened scientific understanding of the replication cycles of these viruses and have revealed several elegant and tightly coordinated post-translational modifications that regulate the activity of viral proteins. The three structural proteins in particular - capsid (C), pre-membrane (prM), and envelope (E) - are subjected to strict regulatory modifications as they progress from translation through virus particle assembly and egress. The timing of proteolytic cleavage events at the C-prM junction directly influences the degree of genomic RNA packaging into nascent virions. Proteolytic maturation of prM by host furin during Golgi transit facilitates rearrangement of the E proteins at the virion surface, exposing the fusion loop and thus increasing particle infectivity. Specific interactions between the prM and E proteins are also important for particle assembly as prM acts as a chaperone facilitating correct conformational folding of E. It is only once prM/E heterodimers form that these proteins may be efficiently secreted. The addition of branched glycans to the prM and E proteins during virion transit also plays a key role in modulating the rate of secretion, pH sensitivity, and infectivity of flavivirus particles. The insights gained from research into post-translational regulation of structural proteins are beginning to be applied in the rational design of improved flavivirus vaccine candidates and make attractive targets for the development of novel therapeutics.
    Journal of General Virology 02/2015; 96(7). DOI:10.1099/vir.0.000097 · 3.18 Impact Factor
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    • "In the context of vector-borne infections, this finding is of particular importance. We already know that to program innate immune response, a mixture of primary responder cells such as macrophages, neutrophils and dendritic cells infiltrate at the site of infection and work together to clear the pathogen which has been transferred through a mosquito bite [31], [32], [33]. One might hypothesize that in these circumstances; SGE-induced apoptosis obstructs primary cells, suppresses effecter mechanisms, and eventually interferes in pathogen clearance. "
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    ABSTRACT: BackgroundIt is widely recognized that the introduction of saliva of bloodsucking arthropods at the site of pathogen transmission might play a central role in vector-borne infections. However, how the interaction between salivary components and the host immune system takes place and which physiological processes this leads to has yet to be investigated. Armigeres subalbatus is one of the prominent types of mosquitoes involved in the transmission of parasitic and viral diseases in humans and animals.Methodology/Principal FindingsUsing murine peritoneal macrophages and lymphocytes, and human peripheral mononuclear cells (PBMCs), this study shows that saliva of the female Ar. subalbatus induces apoptosis via interaction with the Fas receptor within a few hours but without activating caspase-8. The process further activates downstream p38 MAPK signaling, a cascade that leads to the induction of apoptosis in capase-3 dependent manner. We further illustrate that Ar. subalbatus saliva suppresses proinflammatory cytokines without changing IL-10 levels, which might happen as a result of apoptosis.ConclusionsOur study shows for the first time that saliva-induced apoptosis is the leading phenomenon exerted by Ar. subalbatus that impede immune cells leading to the suppression of their effecter mechanism.
    PLoS ONE 07/2012; 7(7):e41145. DOI:10.1371/journal.pone.0041145 · 3.23 Impact Factor
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    • "Although a considerable amount of information is available about humoral defence reactions in bees directed against bacterial and fungal infections, antiviral mechanisms in this social insect are not known at all. Studies in the fruit fly Drosophila and in mosquitos (Aedes aegypti and Anopheles gambiae) have provided convincing evidence that an intrinsic cell defence mechanism based on RNA interference plays a major role in antiviral immune responses against single-stranded and double-stranded RNA viruses [3, 23, 29, 44, 51, 53, 54, 57], whereas reports about the significance of inducible antiviral reactions are somehow contradictory. Sabatier et al. [43] did not detect any of the known AMPs in the haemolymph of Drosophila flies challenged with drosophila C virus (DCV) (a member of the family Dicistroviridae). "
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    ABSTRACT: We have studied the responses of honey bees at different life stages (Apis mellifera) to controlled infection with acute bee paralysis virus and have identified the haemolymph of infected larvae and adult worker bees as the compartment where massive propagation of ABPV occurs. Insects respond with a broad spectrum of induced innate immune reactions to bacterial infections, whereas defence mechanisms based on RNA interference play a major role in antiviral immunity. In this study, we have determined that honey bee larvae and adult workers do not produce a humoral immune reaction upon artificial infection with ABPV, in contrast to control individuals challenged with Escherichia coli. ABPV-infected bees produced neither elevated levels of specific antimicrobial peptides (AMPs), such as hymenoptaecin and defensin, nor any general antimicrobial activity, as revealed by inhibition-zone assays. Additionally, adult bees did not generate melanised nodules upon ABPV infection, an important cellular immune function activated by bacteria and viruses in some insects. Challenge of bees with both ABPV and E. coli showed that innate humoral and cellular immune reactions are induced in mixed infections, albeit at a reduced level. Electronic supplementary material The online version of this article (doi:10.1007/s00705-012-1223-0) contains supplementary material, which is available to authorized users.
    Archives of Virology 01/2012; 157(4):689-702. DOI:10.1007/s00705-012-1223-0 · 2.39 Impact Factor
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