“There is some evidence that people can be reinfected with the four coronaviruses
and that there is no long-lasting immunity,”
SARS has a molecular proofreading system that reduces its mutation rate, and the
new coronavirus’s similarity to SARS at the genomic level suggests it does, too.
“That makes the mutation rate much, much lower than for flu or HIV,” Farzan said.
https://www.statnews.com/2020/02/04/two-scenarios-if-new-coronavirus-isnt-contained/------------------------------------------------------
Thus nsp14-ExoN is essential for replication fidelity, and likely serves either as a direct
mediator or regulator of a more complex RNA proofreading machine, a process previously
unprecedented in RNA virus biology. E
The discovery of a protein distinct from a viral RdRp that regulates replication fidelity also
raises the possibility that RNA genome replication fidelity may be adaptable to differing
replication environments and selective pressures, rather than being a fixed determinant.
Proofreading Exoribonuclease.
Coronaviruses genome also encodes a protein called a replicase which allows
the RNA viral genome to be transcribed into new RNA copies
using the host cell's machinery.
The replicase is the first protein to be made; once the gene encoding the replicase
is translated, translation is stopped by a stop codon.
This is known as a nested transcript. When the mRNA transcript only encodes
one gene, it is monocistronic.
A coronavirus non-structural protein provides extra fidelity to replication because it
confers a proofreading function,[9] which is lacking in RNA-dependent RNA
polymerase enzymes alone.
Sexton NR, Smith EC, Blanc H, Vignuzzi M, Peersen OB, Denison MR (August 2016).
"Homology-Based Identification of a Mutation in the Coronavirus RNA-Dependent RNA
Polymerase That Confers Resistance to Multiple Mutagens".
Journal of Virology. 90 (16): 7415–7428. doi:10.1128/JVI.00080-16. PMC 4984655. PMID 27279608.
CoVs encode a proofreading exonuclease in nonstructural protein 14(nsp14-ExoN),
which confers a greater-than-10
fold increase in fidelity compared to other RNA viruses. It is unknown to what extent the CoV
polymerase (nsp12-RdRp) participates in replication fidelity
multiproteinreplicase-proofreadingcomplex.
Proofreading-deficient coronaviruses adapt for increased fitness over long-term passage
without reversion of exoribonuclease-inactivating mutations
Alanine replacement of the motif I residues (AA-E-D; four nucleotide substitutions) in
murine hepatitis virus (MHV) and severe acute respiratory syndrome (SARS)-CoV yields
viable mutants with impaired replication and fitness, increased mutation rates, and attenuated
virulence in vivo. Despite these impairments, MHV- and SARS-CoV ExoN motif I AA mutants
(ExoN-AA) have not reverted at motif I in diverse in vitro and in vivo environments, suggesting
that profound fitness barriers prevent motif I reversion
The Amazing Diversity of Nidoviruses