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To determine whether virus-transmitting mosquitoes inoculate infectious particles extravascularly or directly into the vascular system, we permitted mosquitoes infected with Rift Valley fever virus to feed on the distal third of the tails of suckling mice. Amputation of the distal half of the tail within 5 min after their being bitten significantly increased mouse survival as compared with that of mice whose tails remained intact. Even when tails were amputated 10 or more min after mosquito feeding, the median time to death was significantly longer in the group with the amputated tails (53.5 hr) than in those mice with intact tails (46.0 hr). Mouse survival did not correlate with ingestion of blood by the infecting mosquito. We conclude that mosquitoes inoculate virus extravascularly, rather than directly into the vascular system, when feeding on a vertebrate host. Such extravascular delivery of virus by a transmitting mosquito may affect viral pathogenesis, antiviral activity, and vaccine efficacy.
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