American Society for Microbiology, Journal of Virology, 4(88), p. 1881-1889, 2014
DOI: 10.1128/jvi.01218-13
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Dengue virus (DENV), the etiologic agent of dengue fever, is transmitted during probing by infected-mosquito bite into human skin. The expectorated viral inoculum also contains an assortment of mosquito salivary proteins that have been shown to modulate host haemostasis and innate immune responses. To examine the potential role of mosquito probing in DENV establishment within the vertebrate host, we inoculated mice intradermally with DENV serotype 2, strain 1232 at sites where Aedes aegypti had or had not probed immediately prior. We assayed these sites 3 hours post inoculation using transcript arrays for the Toll-like receptor, RIG-I-like receptor, and NOD-like receptor signaling pathways of the innate immune system. We then chose Toll-like receptor 7 (TLR7), transcription factor p65 (RelA), interferon (IFN)-γ, and interferon-γ-inducible protein 10 (IP-10) from the arrays for further investigation, assaying these transcripts at 10 minutes, 3 hours, and 6 hours post inoculation. The transcripts for TLR7, RelA, IFN-γ, and IP-10 were significantly down-regulated between two- and three-fold in the group that received mosquito probing relative to the virus only inoculation group at 3 hours post inoculation. A reduction in these transcripts could indicate reduced DENV recognition and antigen presentation, and diminished inhibition of viral replication and spread. Further, mosquito probing resulted in significantly higher viremia titers than in mice that did not receive probing. As such, Ae. aegypti probing has a significant effect on the innate immune response to DENV infection and generates an early immune environment more permissive to the establishment of infection.