Comparative full-length genome sequence analysis of 14 SARS coronavirus isolates and common mutations associated with putative origins of infection.
BACKGROUND
The cause of severe acute respiratory syndrome (SARS) has been identified as a new coronavirus. Whole genome sequence analysis of various isolates might provide an indication of potential strain differences of this new virus. Moreover, mutation analysis will help to develop effective vaccines.


METHODS
We sequenced the entire SARS viral genome of cultured isolates from the index case (SIN2500) presenting in Singapore, from three primary contacts (SIN2774, SIN2748, and SIN2677), and one secondary contact (SIN2679). These sequences were compared with the isolates from Canada (TOR2), Hong Kong (CUHK-W1 and HKU39849), Hanoi (URBANI), Guangzhou (GZ01), and Beijing (BJ01, BJ02, BJ03, BJ04).


RESULTS
We identified 129 sequence variations among the 14 isolates, with 16 recurrent variant sequences. Common variant sequences at four loci define two distinct genotypes of the SARS virus. One genotype was linked with infections originating in Hotel M in Hong Kong, the second contained isolates from Hong Kong, Guangzhou, and Beijing with no association with Hotel M (p<0.0001). Moreover, other common sequence variants further distinguished the geographical origins of the isolates, especially between Singapore and Beijing.


CONCLUSIONS
Despite the recent onset of the SARS epidemic, genetic signatures are emerging that partition the worldwide SARS viral isolates into groups on the basis of contact source history and geography. These signatures can be used to trace sources of infection. In addition, a common variant associated with a non-conservative aminoacid change in the S1 region of the spike protein, suggests that immunological pressures might be starting to influence the evolution of the SARS virus in human populations.
Ruan
Yi Jun
YJ
Genome Institute of Singapore, Singapore.
Wei
Chia Lin
CL
Ee
Ai Ling
AL
Vega
Vinsensius B
VB
Thoreau
Herve
H
Su
Se Thoe Yun
ST
Chia
Jer-Ming
JM
Ng
Patrick
P
Chiu
Kuo Ping
KP
Lim
Landri
L
Zhang
Tao
T
Peng
Chan Kwai
CK
Lin
Ean Oon Lynette
EO
Lee
Ng Mah
NM
Yee
Sin Leo
SL
Ng
Lisa F P
LF
Chee
Ren Ee
RE
Stanton
Lawrence W
LW
Long
Philip M
PM
Liu
Edison T
ET
D000595:Amino Acid Sequence; D001483:Base Sequence; D016679:Genome, Viral; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D016366:Open Reading Frames; D010802:Phylogeny; D011110:Polymorphism, Genetic; D045473:Severe acute respiratory syndrome-related coronavirus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D012846:Singapore