A novel coronavirus associated with severe acute respiratory syndrome.
BACKGROUND
A worldwide outbreak of severe acute respiratory syndrome (SARS) has been associated with exposures originating from a single ill health care worker from Guangdong Province, China. We conducted studies to identify the etiologic agent of this outbreak.


METHODS
We received clinical specimens from patients in seven countries and tested them, using virus-isolation techniques, electron-microscopical and histologic studies, and molecular and serologic assays, in an attempt to identify a wide range of potential pathogens.


RESULTS
None of the previously described respiratory pathogens were consistently identified. However, a novel coronavirus was isolated from patients who met the case definition of SARS. Cytopathological features were noted in Vero E6 cells inoculated with a throat-swab specimen. Electron-microscopical examination revealed ultrastructural features characteristic of coronaviruses. Immunohistochemical and immunofluorescence staining revealed reactivity with group I coronavirus polyclonal antibodies. Consensus coronavirus primers designed to amplify a fragment of the polymerase gene by reverse transcription-polymerase chain reaction (RT-PCR) were used to obtain a sequence that clearly identified the isolate as a unique coronavirus only distantly related to previously sequenced coronaviruses. With specific diagnostic RT-PCR primers we identified several identical nucleotide sequences in 12 patients from several locations, a finding consistent with a point-source outbreak. Indirect fluorescence antibody tests and enzyme-linked immunosorbent assays made with the new isolate have been used to demonstrate a virus-specific serologic response. This virus may never before have circulated in the U.S. population.


CONCLUSIONS
A novel coronavirus is associated with this outbreak, and the evidence indicates that this virus has an etiologic role in SARS. Because of the death of Dr. Carlo Urbani, we propose that our first isolate be named the Urbani strain of SARS-associated coronavirus.
Ksiazek
Thomas G
TG
Special Pathogens Branch, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, USA.
Erdman
Dean
D
Goldsmith
Cynthia S
CS
Zaki
Sherif R
SR
Peret
Teresa
T
Emery
Shannon
S
Tong
Suxiang
S
Urbani
Carlo
C
Comer
James A
JA
Lim
Wilina
W
Rollin
Pierre E
PE
Dowell
Scott F
SF
Ling
Ai-Ee
AE
Humphrey
Charles D
CD
Shieh
Wun-Ju
WJ
Guarner
Jeannette
J
Paddock
Christopher D
CD
Rota
Paul
P
Fields
Barry
B
DeRisi
Joseph
J
Yang
Jyh-Yuan
JY
Cox
Nancy
N
Hughes
James M
JM
LeDuc
James W
JW
Bellini
William J
WJ
Anderson
Larry J
LJ
D000328:Adult; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000821:virology; D002460:Cell Line; D004196:Disease Outbreaks; D005260:Female; D006801:Humans; D008168:Lung / Q000473:pathology / Q000821:virology; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D009960:Oropharynx / Q000821:virology; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000032:analysis; D045473:Severe acute respiratory syndrome-related coronavirus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification* / Q000648:ultrastructure; D045169:Severe Acute Respiratory Syndrome / Q000453:epidemiology / Q000473:pathology / Q000821:virology*
D012367:RNA, Viral