Studies on persisting infections by human respiratory Paramyxoviruses

Abstract

Infections caused by human paramyxoviruses have great impact in public health, but little is known about their pathogenesis. Evidence recently produced by our group suggests that these agents frequently persist in lymphoid tissue of human tonsils. Such tonsillar persistence of paramyxoviruses is importante because of the possible pathogenic and immunologic consequences, as well as because of the potential impact of asymptomatic carriers shedding paramyxovirus in the community. The present project, strongly based on preliminary data, aims at investigating the persistence of a respiratory paramyxoviroma in lymphoid tonsillar tissues, shedding light on mechanisms of this persistence, an area virtually unexplored in human virology. We expect to confirm presence of replication markers of human respiratory syncytial virus (HRSV), human metapneumovirus (HMPV) and human parainfluenza virus (HPIV). The paramyxoviral RNA profiling will generate the polyssomal active transcriptome of these agents. The host cell phenotypes and intracelular localization of replication will be determined. Also, the presence of paramyxoviral functional proteins diffused beyond the infected cells will be assessed. We will also develop a fluorescent HRSV clone by reverse genetics and establish ex vivo and in vivo models of HRSV infection. (AU)