Innate Immune Control of West Nile Virus Infection

Article (PDF Available)inCellular Microbiology 13(11):1648-58 · July 2011with26 Reads
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.


    • "The innate immune system is broadly conserved across insects and mammals [54][55][56][57][58][59]. It has been well documented that an innate immune response is activated in mosquitoes following infection by a diverse array of pathogens [60][61][62][63][64][65][66]. However, this response has been most often shown to limit pathogenesis in the mosquito host, but does not necessarily prevent them from becoming competent vectors for subsequent pathogen transmission to a human host. "
    [Show abstract] [Hide abstract] ABSTRACT: Dengue (DENV), yellow fever, chikungunya, and Zika virus transmission to humans by a mosquito host is confounded by both intrinsic and extrinsic variables. Besides virulence factors of the individual arboviruses, likelihood of virus transmission is subject to variability in the genome of the primary mosquito vector, Aedes aegypti. The “vectorial capacity” of A. aegypti varies depending upon its density, biting rate, and survival rate, as well as its intrinsic ability to acquire, host and transmit a given arbovirus. This intrinsic ability is known as “vector competence”. Based on whole transcriptome analysis, several genes and pathways have been predicated to have an association with a susceptible or refractory response in A. aegypti to DENV infection. However, the functional genomics of vector competence of A. aegypti is not well understood, primarily due to lack of integrative approaches in genomic or transcriptomic studies. In this review, we focus on the present status of genomics studies of DENV vector competence in A. aegypti as limited information is available relative to the other arboviruses. We propose future areas of research needed to facilitate the integration of vector and virus genomics and environmental factors to work towards better understanding of vector competence and vectorial capacity in natural conditions.
    Full-text · Article · Oct 2016
    • "We have chosen to concentrate on vertebrate hosts because, unlike the lifelong infections established in arthropods, arbovirus infections in vertebrates are usually acute, and the virus is cleared after a period of days (figure 2). Arbovirus infections in vertebrates are initially controlled by the innate immune response; most also stimulate an adaptive immune response that prevents homologous re-infection [20,26272829. Some arboviruses can produce chronic infections that recrudesce at intervals, enabling survival over seasons, such as winters, that are inimical to vector activity303132, but these are the exception to the rule of transient infection. "
    [Show abstract] [Hide abstract] ABSTRACT: Arthropod-borne viruses (arboviruses) are maintained in a cycle of alternating transmission between vertebrate hosts and arthropod vectors. Arboviruses possess RNA genomes capable of rapid diversification and adaptation, and the between-host trade-offs inherent to host alternation impose well-documented constraints on arbovirus evolution. Here, we investigate the less well-studied within-host trade-offs that shape arbovirus replication dynamics and transmission. Arboviruses generally establish lifelong infection in vectors but transient infection of variable magnitude (i.e. peak virus concentration) and duration in vertebrate hosts. In the majority of experimental infections of vertebrate hosts, both the magnitude and duration of arbovirus replication depended upon the dose of virus administered, with increasing dose resulting in greater magnitude but shorter duration of viraemia. This pattern suggests that the vertebrate immune response imposes a trade-off between the height and breadth of the virus replication curve. To investigate the impact of this trade-off on transmission, we used a simple modelling approach to contrast the effect of 'tortoise' (low magnitude, long duration viraemia) and 'hare' (high magnitude, short duration viraemia) arbovirus replication strategies on transmission. This model revealed that, counter to previous theory, arboviruses that adopt a tortoise strategy have higher rates of persistence in both host and vector populations. © 2015 The Author(s) Published by the Royal Society. All rights reserved.
    Full-text · Article · Aug 2015
    • "Such a hypothesis remains to be properly explored, although it would be intriguing to investigate whether partially matured DENV displays a greater capacity to infect DC-SIGN-expressing cells. 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). In both Aedes and Culex mosquitoes, the soluble galactosespecific lectin mosGCTL-1 binds to glycosylated WNV (but apparently not to DENV) in the haemolymph and then coordinates with a cell-surface CD45 phosphatase homologue mosPTP-1 to facilitate virus entry (Cheng et al., 2010). "
    [Show abstract] [Hide abstract] 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.
    Full-text · Article · Feb 2015
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