Eilat virus, a unique alphavirus with host range restricted to insects by RNA replication

Institute for Human Infections and Immunity and Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 08/2012; 109(36):14622-7. DOI: 10.1073/pnas.1204787109
Source: PubMed


Most alphaviruses and many other arboviruses are mosquito-borne and exhibit a broad host range, infecting many different vertebrates including birds, rodents, equids, humans, and nonhuman primates. Consequently, they can be propagated in most vertebrate and insect cell cultures. This ability of arboviruses to infect arthropods and vertebrates is usually essential for their maintenance in nature. However, several flaviviruses have recently been described that infect mosquitoes but not vertebrates, although the mechanism of their host restriction has not been determined. Here we describe a unique alphavirus, Eilat virus (EILV), isolated from a pool of Anopheles coustani mosquitoes from the Negev desert of Israel. Phylogenetic analyses placed EILV as a sister to the Western equine encephalitis antigenic complex within the main clade of mosquito-borne alphaviruses. Electron microscopy revealed that, like other alphaviruses, EILV virions were spherical, 70 nm in diameter, and budded from the plasma membrane of mosquito cells in culture. EILV readily infected a variety of insect cells with little overt cytopathic effect. However, in contrast to typical mosquito-borne alphaviruses, EILV could not infect mammalian or avian cell lines, and viral as well as RNA replication could not be detected at 37 °C or 28 °C. Evolutionarily, these findings suggest that EILV lost its ability to infect vertebrate cells. Thus, EILV seems to be mosquito-specific and represents a previously undescribed complex within the genus Alphavirus. Reverse genetic studies of EILV may facilitate the discovery of determinants of alphavirus host range that mediate disease emergence.

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Available from: Gustavo Palacios, Feb 20, 2015
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    • "Our in vitro results with heterologous superinfecting viruses do not support this hypothesis. The SINV nsP2/3 cleavage site is identical to that of EILV and its nsP1/2 site differs only by one amino acid; consequently there should be greater exclusion of SINV than of WEEV, whose nsP cleavage sites display greater sequence divergence (Fig. 5) (Nasar et al., 2012). Superinfection with SINV and WEEV resulted in almost identical levels of reduction in virus production and delays in replication kinetics (Figs. 5 and 6). "
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    ABSTRACT: Most alphaviruses are mosquito-borne and exhibit a broad host range, infecting many different vertebrates including birds, rodents, equids, and humans. Occasionally, alphaviruses can spill over into the human population and cause disease characterized by debilitating arthralgia or fatal encephalitis. Recently, a unique alphavirus, Eilat virus (EILV), was described that readily infects mosquito but not vertebrate cell lines. Here, we investigated the ability of EILV to induce superinfection exclusion. Prior infection of C7/10 (Aedes albopictus) cells with EILV induced homologous and heterologous interference, reducing the virus titers of heterologous superinfecting viruses (SINV, VEEV, EEEV, WEEV, and CHIKV) by ~10-10,000 fold and delaying replication kinetics by 12-48h. Similar to in vitro infection, prior in vivo EILV infection of Aedes aegypti mosquitoes delayed dissemination of chikungunya virus for 3 days. This is the first evidence of heterologous interference induced by a mosquito-specific alphavirus in vitro and in vivo. Copyright © 2015 Elsevier Inc. All rights reserved.
    Virology 06/2015; 484:51-58. DOI:10.1016/j.virol.2015.05.009 · 3.32 Impact Factor
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    • "The genus Alphavirus within the family Togaviridae is comprised of 31 arthropod-borne viruses with a worldwide distribution (Powers et al., 2012; Nasar et al., 2012). Of these viruses, four are endemic to North America: eastern equine encephalitis virus (EEEV), western equine encephalitis virus (WEEV), Highlands J virus (HJV), and Fort Morgan virus (FMV) (Weaver et al., 1997). "
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    ABSTRACT: Western equine encephalitis virus (WEEV), Highlands J virus (HJV), and Fort Morgan virus (FMV) are the sole representatives of the WEE antigenic complex of the genus Alphavirus, family Togaviridae, that are endemic to North America. All three viruses have their ancestry in a recombination event involving eastern equine encephalitis virus (EEEV) and a Sindbis (SIN)-like virus that gave rise to a chimeric alphavirus that subsequently diversified into the present-day WEEV, HJV, and FMV. Here, we present a comparative analysis of the genetic, ecological, and evolutionary relationships among these recombinant-origin viruses, including the description of a nsP4 polymerase mutation in FMV that allows it to circumvent the host range barrier to Asian tiger mosquito cells, a vector species that is normally refractory to infection. Notably, we also provide evidence that the recombination event that gave rise to these three WEEV antigenic complex viruses may have occurred in North America.
    Virology 11/2014; 474. DOI:10.1016/j.virol.2014.10.024 · 3.32 Impact Factor
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    • "In addition to dualhost (vertebrate and vector-infecting viruses) mosquito-borne viruses, a number of mosquito-specific viruses have been identified for which the capacity for replication in vertebrate cells has not been observed. These viruses have been described extensively in the family Flaviviridae (Cook et al., 2012) and recently in the families Togaviridae (Nasar et al., 2012) and Bunyaviridae (Marklewitz et al., 2013). The discovery of these viruses should allow for in-depth study of mechanisms of vertical transmission of different viral families in mosquitoes as well as novel mechanisms of RNAi antagonism of vector species in addition to the fundamental elements that restrict host range of these viruses. "
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    ABSTRACT: Arthropod-borne viruses (arboviruses) are transmitted between vertebrate hosts and arthropod vectors. An inherently complex interaction among virus, vector, and the environment determines successful transmission of the virus. Once believed to be "flying syringes," recent advances in the field have demonstrated that mosquito genetics, microbiota, salivary components, and mosquito innate immune responses all play important roles in modulating arbovirus transmissibility. The literature on the interaction among virus, mosquito, and environment has expanded dramatically in the preceding decade and the utilization of next-generation sequencing and transgenic vector methodologies assuredly will increase the pace of knowledge acquisition in this field. This chapter outlines the interplay among the three factors in both direct physical and biochemical manners as well as indirectly through superinfection barriers and altered induction of innate immune responses in mosquito vectors. The culmination of the aforementioned interactions and the arms race between the mosquito innate immune response and the capacity of arboviruses to antagonize such a response ultimately results in the subjugation of mosquito cells for viral replication and subsequent transmission.
    Advances in Virus Research 04/2014; 89:39-83. DOI:10.1016/B978-0-12-800172-1.00002-1 · 4.57 Impact Factor
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