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Dengue virus type 2: Replication and tropisms in orally infected Aedes aegypti mosquitoes

Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado 80523-1692, USA. <>
BMC Microbiology (Impact Factor: 2.73). 01/2007; 7:9. DOI: 10.1186/1471-2180-7-9
Source: PubMed

ABSTRACT

To be transmitted by its mosquito vector, dengue virus (DENV) must infect midgut epithelial cells, replicate and disseminate into the hemocoel, and finally infect the salivary glands, which is essential for transmission. The extrinsic incubation period (EIP) is very relevant epidemiologically and is the time required from the ingestion of virus until it can be transmitted to the next vertebrate host. The EIP is conditioned by the kinetics and tropisms of virus replication in its vector. Here we document the virogenesis of DENV-2 in newly-colonized Aedes aegypti mosquitoes from Chetumal, Mexico in order to understand better the effect of vector-virus interactions on dengue transmission.
After ingestion of DENV-2, midgut infections in Chetumal mosquitoes were characterized by a peak in virus titers between 7 and 10 days post-infection (dpi). The amount of viral antigen and viral titers in the midgut then declined, but viral RNA levels remained stable. The presence of DENV-2 antigen in the trachea was positively correlated with virus dissemination from the midgut. DENV-2 antigen was found in salivary gland tissue in more than a third of mosquitoes at 4 dpi. Unlike in the midgut, the amount of viral antigen (as well as the percent of infected salivary glands) increased with time. DENV-2 antigen also accumulated and increased in neural tissue throughout the EIP. DENV-2 antigen was detected in multiple tissues of the vector, but unlike some other arboviruses, was not detected in muscle.
Our results suggest that the EIP of DENV-2 in its vector may be shorter that the previously reported and that the tracheal system may facilitate DENV-2 dissemination from the midgut. Mosquito organs (e.g. midgut, neural tissue, and salivary glands) differed in their response to DENV-2 infection.

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Available from: Ma Isabel Salazar, Mar 24, 2014
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    • "We selected the CCL-125 larval cell line for our studies because of its availability, potential infectivity, and epithelial-like morphology [10]. It is relevant to transovarial transmission of virus [16] and may mimic responses to virus by other epithelial-like cells that are present in the midgut and salivary glands. Despite the limitations of the present study, we provide evidence of a potentially novel innate immune signaling pathway in an invertebrate model that partially mimics a related sodium channeldependent mechanism in human macrophages. "
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    ABSTRACT: Recent work demonstrated that a splice variant of a human macrophage voltage-gated sodium channel expressed on endosomes acts as an intracellular sensor for dsRNA, a viral-associated molecular pattern. Here our goal was to identify a candidate gene in a clinically relevant invertebrate model with related cellular and pattern recognition properties. The para gene in drosophila and other insects encodes voltage-gated sodium channels with similar electrophysiological properties to those found in vertebrate excitable membranes. A database search revealed that the AAEL006019 gene in Aedes aegypti, the yellow fever mosquito, encodes a voltage-gated sodium channel that is distinct from genes that encode para-like sodium channels. As compared to para-like channels, the protein products from this gene have deletions in the N-terminus and in the DII-DIII linker region. When over-expressed in an Aedes aegypti cell line, CCL-125, the AAEL006019 channel demonstrated cytoplasmic expression on vesicular-like organelles. Electrophysiologic analysis revealed that the channel mediates small inward currents that are enhanced by synthetic mimics of viral-derived ssRNA, R848 and ORN02, but not the dsRNA mimic, poly I:C. R848 treatment of CCL-125 cells that express high levels of the channels led to increased expression of RelA and Ago2, two mediators of insect innate immunity. These results suggest that the AAEL006019 channel acts as an intracellular pathogen sensor for ssRNA molecular patterns. Copyright © 2015. Published by Elsevier Inc.
    Preview · Article · Jun 2015 · Biochemical and Biophysical Research Communications
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    • "It then spreads through the hemolymph. Salazar et al. analyzed the tropism of the DENV-2 in A. aegypti by immunofluorescence and noted infection mostly in intestine, salivary glands, abdomen, neural tissue and just a slight infection in the Malpighian tubules, indicating the existence of a tropism for some tissues in the mosquito, as is the case for humans [109]. First DENV interacts with cell receptor as in humans, followed by penetration through endocytosis [2] [110]. "

    Full-text · Dataset · Apr 2015
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    • "It then spreads through the hemolymph. Salazar et al. analyzed the tropism of the DENV-2 in A. aegypti by immunofluorescence and noted infection mostly in intestine, salivary glands, abdomen, neural tissue and just a slight infection in the Malpighian tubules, indicating the existence of a tropism for some tissues in the mosquito, as is the case for humans [109]. First DENV interacts with cell receptor as in humans, followed by penetration through endocytosis [2] [110]. "

    Full-text · Dataset · Mar 2015
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