Amino acid substitutions in S2 region enhance SARS-CoV infectivity in rat ACE2-expressing cells

Department of Virology I, Department of Virology III, and Center for Pathogen Genomics, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashimurayama, Tokyo 208-0011, Japan

^* To whom correspondence should be addressed. Email: fukushi{at}nih.go.jp.

	Abstract

To clarify the molecular basis of the severe acute respiratory syndrome coronavirus (SARS-CoV) adaptation to different host species, we serially passaged SARS-CoV in rat ACE2-expressing cells. After 15 passages, the virus (Rat-P15) became 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 pseudotypes-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.