RESUMEN
The initial steps of Venezuelan equine encephalitis virus (VEE) spread from inoculation in the skin to the draining lymph node have been characterized. By using green fluorescent protein and immunocytochemistry, dendritic cells in the draining lymph node were determined to be the primary target of VEE infection in the first 48 h following inoculation. VEE viral replicon particles, which can undergo only one round of infection, identified Langerhans cells to be the initial set of cells infected by VEE directly following inoculation. These cells are resident dendritic cells in the skin, which migrate to the draining lymph node following activation. A point mutation in the E2 glycoprotein gene of VEE that renders the virus avirulent and compromises its ability to spread beyond the draining lymph blocked the appearance of virally infected dendritic cells in the lymph node in vivo. A second-site suppressor mutation that restores viral spread to lymphoid tissues and partially restore virulence likewise restored the ability of VEE to infect dendritic cells in vivo.
Asunto(s)
Células Dendríticas/virología , Virus de la Encefalitis Equina Venezolana/patogenicidad , Animales , Línea Celular , Fraccionamiento Químico , Cricetinae , Virus de la Encefalitis Equina Venezolana/genética , Encefalomielitis Equina Venezolana/patología , Encefalomielitis Equina Venezolana/virología , Proteínas Fluorescentes Verdes , Inyecciones Subcutáneas , Células de Langerhans/virología , Proteínas Luminiscentes , Ganglios Linfáticos/citología , Ratones , Proteínas del Envoltorio Viral/genética , Proteínas del Envoltorio Viral/fisiologíaRESUMEN
Present methods for assessment of the attack phase of malaria eradication are inadequate, particularly lacking any objective parasitological criteria of success. The most objective of the criteria used has been the absence of infections among infants. This has always been subject to the drawback that it is rarely possible to get enough infants to secure a statistically reliable result. Moreover, all the variants used have been subject to the difficulty that it is impossible to prove a total negative without examination of the entire population, and there has always been uncertainty on the scale of examination which was required for adequacy. The authors have therefore undertaken a careful review of parasitological criteria for the interruption of transmission, with the intention of producing precise and objective criteria from which clear-cut conclusions could be reached on the adequacy of the attack mechanism. In theory the total interruption of transmission should produce readily foreseeable results in terms of the progressive decline of the parasite rate, total absence of fresh infections, and immediate reduction to zero of the parasite rate among infants born after the start of the campaign. However, since it is statistically impossible to prove absolute success which is tolerable for the purposes of eradication, and statistically sound criteria should be set up to enable the