West Nile virus is a single-stranded RNA (ssRNA) virus that enters the host through a mosquito bite and can infect most tissues, including the brain. Host responses to viral infections often involve TLRs; these proteins sense molecules derived from pathogens and then transduce a signal, in most cases through myeloid differentiation primary-response gene 88 (MyD88), to elicit an immune response. Because TLR7 can recognize ssRNA and is known to play a part in the defence against other viral pathogens, Town and colleagues tested whether TLR7 had a role in the response to West Nile virus infection. They found that TLR7-deficient and MyD88-deficient mice were more susceptible to West Nile virus infection; deletion of the gene encoding TLR9, which has been shown to sense viral DNA, had no effect on the outcome of the infection. Viral load was significantly higher in both TLR7-deficient and MyD88-deficient mice, particularly in the brain and liver. Serum levels of several innate immune cytokines were increased in the absence of TLR7, but curiously the levels of IL-12p40 (a shared component of IL-12 and IL-23; also known as IL-12β) and IL-23 were decreased in mutant mice. The authors noticed that in infected wild-type brains and livers, leukocytes and macrophages were in close proximity to infected neurons, sometimes even overlapping, but they did not detect this apposition in TLR7-deficient or MyD88-deficient mice, even though such mice had a higher virus burden. Peritoneal injection of the mutant mice with thioglycollate, which induces macrophage migration, showed that mutant mouse macrophages could still respond to a chemotactic signal.
...IL-23-deficient and MyD88-deficient mice were also more susceptible to viral infection...
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