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2020 ; 11
(4
): ä Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Discovery and Genomic Characterization of a 382-Nucleotide Deletion in ORF7b and
ORF8 during the Early Evolution of SARS-CoV-2
#MMPMID32694143
Su YCF
; Anderson DE
; Young BE
; Linster M
; Zhu F
; Jayakumar J
; Zhuang Y
; Kalimuddin S
; Low JGH
; Tan CW
; Chia WN
; Mak TM
; Octavia S
; Chavatte JM
; Lee RTC
; Pada S
; Tan SY
; Sun L
; Yan GZ
; Maurer-Stroh S
; Mendenhall IH
; Leo YS
; Lye DC
; Wang LF
; Smith GJD
mBio
2020[Jul]; 11
(4
): ä PMID32694143
show ga
To date, limited genetic changes in the severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) genome have been described. Here, we report a
382-nucleotide (nt) deletion in SARS-CoV-2 that truncates open reading frame 7b
(ORF7b) and ORF8, removing the ORF8 transcription regulatory sequence (TRS) and
eliminating ORF8 transcription. The earliest 382-nt deletion variant was detected
in Singapore on 29 January 2020, with the deletion viruses circulating in the
country and accounting for 23.6% (45/191) of SARS-CoV-2 samples screened in this
study. SARS-CoV-2 with the same deletion has since been detected in Taiwan, and
other ORF7b/8 deletions of various lengths, ranging from 62 nt to 345 nt, have
been observed in other geographic locations, including Australia, Bangladesh, and
Spain. Mutations or deletions in ORF8 of SARS-CoV have been associated with
reduced replicative fitness and virus attenuation. In contrast, the SARS-CoV-2
382-nt deletion viruses showed significantly higher replicative fitness in vitro
than the wild type, while no difference was observed in patient viral load,
indicating that the deletion variant viruses retained their replicative fitness.
A robust antibody response to ORF8 has been observed in SARS-CoV-2 infection,
suggesting that the emergence of ORF8 deletions may be due to immune-driven
selection and that further deletion variants may emerge during the sustained
transmission of SARS-CoV-2 in humans.IMPORTANCE During the SARS epidemic in
2003/2004, a number of deletions were observed in ORF8 of SARS-CoV, and
eventually deletion variants became predominant, leading to the hypothesis that
ORF8 was an evolutionary hot spot for adaptation of SARS-CoV to humans. However,
due to the successful control of the SARS epidemic, the importance of these
deletions for the epidemiological fitness of SARS-CoV in humans could not be
established. The emergence of multiple SARS-CoV-2 strains with ORF8 deletions,
combined with evidence of a robust immune response to ORF8, suggests that the
lack of ORF8 may assist with host immune evasion. In addition to providing a key
insight into the evolutionary behavior of SARS-CoV-2 as the virus adapts to its
new human hosts, the emergence of ORF8 deletion variants may also impact
vaccination strategies.