title: Pathogenesis of Lassa fever virus infection: I. Susceptibility of mice to recombinant Lassa Gp/LCMV chimeric virus.
abstract: Lassa virus (LASV) is a BSL-4 restricted agent. To allow study of infection by LASV under BSL-2 conditions, we generated a recombinant virus in which the LASV glycoprotein (Gp) was placed on the backbone of lymphocytic choriomeningitis virus (LCMV) Cl13 nucleoprotein, Z and polymerase genes (rLCMV Cl13/LASV Gp). The recombinant virus displayed high tropism for dendritic cells following in vitro or in vivo infection. Inoculation of immunocompetent adults resulted in an acute infection, generation of virus-specific CD8(+) T cells and clearance of the infection. Inoculation of newborn mice with rLCMV Cl13/LASV Gp resulted in a life-long persistent infection. Interestingly, adoptive transfer of rLCMV Cl13/LASV Gp immune memory cells into such persistently infected mice failed to purge virus but, in contrast, cleared virus from mice persistently infected with wt LCMV Cl13.
authors.affiliation: Viral-Immunobiology Laboratory, Department of Immunology and Microbial Sciences, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. Andrew.Lee@utsouthwestern.edu
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Lee
authors.forename: Justin
authors.initials: J
authors.lastname: Cruite
authors.forename: Megan J
authors.initials: MJ
authors.lastname: Welch
authors.forename: Brian
authors.initials: B
authors.lastname: Sullivan
authors.forename: Michael B A
authors.initials: MB
authors.lastname: Oldstone
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002908:Chronic Disease; D003713:Dendritic Cells / Q000821:virology; D004195:Disease Models, Animal; D007835:Lassa Fever / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D007836:Lassa virus / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity* / Q000502:physiology; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D011995:Recombination, Genetic; D014759:Viral Envelope Proteins / Q000235:genetics; D056189:Viral Tropism
chemical_list: D014759:Viral Envelope Proteins; C066508:glycoprotein gp1, lassa virus; C077198:glycoprotein gp2, lassa virus