IMPORTANCE OF LOCALIZED SKIN INFECTION IN TICK-BORNE ENCEPHALITIS-VIRUS TRANSMISSION

Arboviruses are transmitted to vertebrates by the ''bite'' of infected arthropods. Events at the site of virus deposition are largely unknow n despite increasing evidence that blood-sucking arthropods immunomodu late their skin site of feeding. This question is particularly relevan t for ixodid ticks that feed for several days. To examine events under conditions mimicking tick-borne encephalitis (TBE) virus transmission in nature (i.e., infected and uninfected lxodes ricinus ticks feeding on the same animal), infected adult and uninfected nymphal ticks were placed in one retaining chamber (skin site A) and uninfected nymphs w ere placed within a second chamber posteriorly (skin site B) on two na tural host species, yellow-necked field mice (Apodemus flavicollis) an d bank voles (Clethrionomys glareolus). Virus transmission from infect ed to uninfected cofeeding ticks was correlated with infection in the skin site of lick feeding. Furthermore virus was recruited preferentia lly to the site in which ticks were feeding compared with uninfested s kin sites. Viremia did not correspond with a generalized infection of the skin; virus was not detected in an uninfested skin site (C) of 12/ 13 natural hosts that had viremia levels greater than or equal to 2.0 log(10) ic mouse LD(50)/0.02 ml blood. To characterize infected cells, laboratory mouse strains were infested with infected licks and then e xplants were removed from selected skin sites and floated on culture m edium. Numerous leukocytes were found to migrate from the skin explant s of tick feeding sites. Two-color immunocytochemistry revealed viral antigen in both migratory Langerhans cells and neutrophils; in additio n, the migratory monocyte/macrophages were shown to produce infectious virus. The results indicate that the local skin site of tick feeding is an important focus of viral replication early after TBE virus trans mission by ticks. Cellular infiltration of tick feeding sites, and the migration of cells from such sites, may provide a vehicle for transmi ssion between infected and uninfected cofeeding ticks that is independ ent of a patent viremia. The data support the hypothesis that viremia is a product, rather than a prerequisite, of tick-borne virus transmis sion. (C) 1996 Academic Press, Inc.