  SARS-CoV is believed to originate from civets and was thought to have been
eliminated as a threat after the 2003 outbreak. Here, we show that human
SARS-CoV (huSARS-CoV) originated directly from bats, rather than civets, by a
cross-species jump in 1991, and formed a human-adapted strain in 1998. Since
then huSARS-CoV has evolved further into highly virulent strains with genotype
T and a 29-nt deletion mutation, and weakly virulent strains with genotype C
but without the 29-nt deletion. The former can cause pneumonia in humans and
could be the major causative pathogen of the SARS outbreak, whereas the latter
might not cause pneumonia in humans, but evolved the ability to co-utilize
civet ACE2 as an entry receptor, leading to interspecies transmission between
humans and civets. Three crucial time points - 1991, for the cross-species jump
from bats to humans; 1998, for the formation of the human-adapted SARS-CoV; and
2003, when there was an outbreak of SARS in humans - were found to associate
with anomalously low annual precipitation and high temperatures in Guangdong.
Anti-SARS-CoV sero-positivity was detected in 20% of all the samples tested
from Guangzhou children who were born after 2005, suggesting that weakly
virulent huSARS-CoVs might still exist in humans. These existing but undetected
SARS-CoVs have a large potential to evolve into highly virulent strains when
favorable climate conditions occur, highlighting a potential risk for the
reemergence of SARS.
