Studies on the pathogenesis of dengue infection in monkeys. 3. Sequential distribution of virus in primary and heterologous infections.

Abstract

Sequential localization in tissue of dengue viruses was studied in 31 primary and eight secondary infections in rhesus monkeys. In ten animals sacrificed before viremia in primary infection, virus was rapidly disseminated from the inoculation site to regional lymph nodes and then to lymphatic tissue throughout the body. Early in the viremic period virus was recovered only from lymph nodes, while two to three days later there was evidence of dissemination to skin and other tissues. Virus was recovered from skin, lymph nodes, and several leukocyte-rich tissues for three days after the termination of viremia. Sequential tissue studies showed virus in circulating leukocytes, in multiple skin sites, and in the upper respiratory tract at the end or just after the termination of viremia. In preliminary experiments, the rate of recovery of virus from tissues was higher in secondary infection than in primary infection. This study suggests that the amount of intracellular infection increases toward the end of the viremic period, abruptly ending one to two days later. This phenomenon correlates closely with the time of onset of shock in human dengue infection.