title: Mucosal arenavirus infection of primates can protect them from lethal hemorrhagic fever.
abstract: Arenaviruses are transmitted from rodents to human beings by blood or mucosal exposure. The most devastating arenavirus in terms of human disease is Lassa fever virus, causing up to 300,000 annual infections in West Africa. We used a model for Lassa fever in which Rhesus macaques were infected with a related virus, lymphocytic choriomeningitis virus (LCMV). Our goals were to determine the outcome of infection after mucosal inoculation and later lethal challenge, to characterize protective immune responses, and to test cross-protection between a virulent (LCMV-WE) and an avirulent (LCMV-ARM) strain of virus. Although intravenous infections in the monkey model were uniformly lethal, intragastric infections recapitulated the spectrum of clinical outcomes seen in human exposure to Lassa fever virus: death, recovery from disease, and most often, subclinical infection. Plaque neutralization, ELISA, lymphocyte proliferation, and chromium-release assays were used to monitor humoral and cellular immune responses. Cross protection between the two strains was observed. The three out of seven monkeys that experienced protection were also the three with the strongest cell-mediated immunity.
authors.affiliation: Institute of Human Virology, University of Maryland Biotechnology Institute, Baltimore, Maryland 21201, USA.
authors.forename: Juan D
authors.initials: JD
authors.lastname: Rodas
authors.forename: Igor S
authors.initials: IS
authors.lastname: Lukashevich
authors.forename: Juan C
authors.initials: JC
authors.lastname: Zapata
authors.forename: Cristiana
authors.initials: C
authors.lastname: Cairo
authors.forename: Ilia
authors.initials: I
authors.lastname: Tikhonov
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Djavani
authors.forename: C David
authors.initials: CD
authors.lastname: Pauza
authors.forename: Maria S
authors.initials: MS
authors.lastname: Salvato
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D001117:Arenaviridae Infections / Q000276:immunology* / Q000821:virology; D016923:Cell Death; D003429:Cross Reactions; D003602:Cytotoxicity, Immunologic; D004798:Enzymes / Q000097:blood; D005260:Female; D005753:Gastric Mucosa / Q000821:virology*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000502:physiology; D008213:Lymphocyte Activation; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology* / Q000472:pathogenicity*; D008253:Macaca mulatta; D009500:Neutralization Tests; D012367:RNA, Viral / Q000097:blood; D014766:Viremia; D014774:Virulence
chemical_list: D000914:Antibodies, Viral; D004798:Enzymes; D012367:RNA, Viral