title: A severe acute respiratory syndrome-associated coronavirus-specific protein enhances virulence of an attenuated murine coronavirus.
abstract: Most animal species that can be infected with the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) do not reproducibly develop clinical disease, hindering studies of pathogenesis. To develop an alternative system for the study of SARS-CoV, we introduced individual SARS-CoV genes (open reading frames [ORFs]) into the genome of an attenuated murine coronavirus. One protein, the product of SARS-CoV ORF6, converted a sublethal infection to a uniformly lethal encephalitis and enhanced virus growth in tissue culture cells, indicating that SARS-CoV proteins function in the context of a heterologous coronavirus infection. Furthermore, these results suggest that the attenuated murine coronavirus lacks a virulence gene residing in SARS-CoV. Recombinant murine coronaviruses cause a reproducible and well-characterized clinical disease, offer virtually no risk to laboratory personnel, and should be useful for elucidating the role of SARS-CoV nonstructural proteins in viral replication and pathogenesis.
authors.affiliation: Department of Pediatrics, University of Iowa, Medical Laboratories 2042, Iowa City, 52242, USA.
authors.forename: Lecia
authors.initials: L
authors.lastname: Pewe
authors.forename: Haixia
authors.initials: H
authors.lastname: Zhou
authors.forename: Jason
authors.initials: J
authors.lastname: Netland
authors.forename: Chandra
authors.initials: C
authors.lastname: Tangudu
authors.forename: Heidi
authors.initials: H
authors.lastname: Olivares
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.forename: Dwight
authors.initials: D
authors.lastname: Look
authors.forename: Thomas
authors.initials: T
authors.lastname: Gallagher
authors.forename: Stanley
authors.initials: S
authors.lastname: Perlman
mesh_terms: D000818:Animals; D002460:Cell Line; D018352:Coronavirus Infections / Q000821:virology*; D004195:Disease Models, Animal; D004660:Encephalitis / Q000821:virology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D006517:Murine hepatitis virus / Q000235:genetics / Q000472:pathogenicity*; D016366:Open Reading Frames / Q000235:genetics; D016865:Reassortant Viruses / Q000472:pathogenicity*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000737:chemistry* / Q000472:pathogenicity* / Q000502:physiology; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism; D014774:Virulence; D014779:Virus Replication
chemical_list: D017361:Viral Nonstructural Proteins