A severe acute respiratory syndrome-associated coronavirus-specific protein enhances virulence of an attenuated murine coronavirus.
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.
Pewe
Lecia
L
Department of Pediatrics, University of Iowa, Medical Laboratories 2042, Iowa City, 52242, USA.
Zhou
Haixia
H
Netland
Jason
J
Tangudu
Chandra
C
Olivares
Heidi
H
Shi
Lei
L
Look
Dwight
D
Gallagher
Thomas
T
Perlman
Stanley
S
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
D017361:Viral Nonstructural Proteins