Amino acid substitutions in the s2 region enhance severe acute respiratory syndrome coronavirus infectivity in rat angiotensin-converting enzyme 2-expressing cells.
To clarify the molecular basis of severe acute respiratory syndrome coronavirus (SARS-CoV) adaptation to different host species, we serially passaged SARS-CoV in rat angiotensin-converting enzyme 2 (ACE2)-expressing cells. After 15 passages, the virus (Rat-P15) came to replicate effectively in rat ACE2-expressing cells. Two amino acid substitutions in the S2 region were found on the Rat-P15 S gene. Analyses of the infectivity of the pseudotype-bearing S protein indicated that the two substitutions in the S2 region, especially the S950F substitution, were responsible for efficient infection. Therefore, virus adaptation to different host species can be induced by amino acid substitutions in the S2 region.
Fukushi
Shuetsu
S
Special Pathogens Laboratory, Department of Virology I, Center for Pathogens Genomics, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashimurayama, Tokyo 208-0011, Japan. fukushi@nih.go.jp
Mizutani
Tetsuya
T
Sakai
Kouji
K
Saijo
Masayuki
M
Taguchi
Fumihiro
F
Yokoyama
Masaru
M
Kurane
Ichiro
I
Morikawa
Shigeru
S
D019943:Amino Acid Substitution; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D002460:Cell Line; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D045473:Severe acute respiratory syndrome-related coronavirus / Q000235:genetics / Q000502:physiology*; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics*; D014779:Virus Replication / Q000235:genetics*
D008562:Membrane Glycoproteins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; C578557:spike glycoprotein, SARS-CoV; C578553:spike protein, mouse hepatitis virus; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2