J Bei1, G Xu2, J Chang2, X Wang3, D Qiu4, J Ruan3, X Li2, S Gao2. 1. Agro-Biological Gene Research Center, Guangdong Academy of Agricultural Sciences, Guangzhou 510275, China. 2. College of Life Sciences, Nankai University, Tianjin 300071, China. 3. School of Mathematical Sciences, Nankai University, Tianjin 300071, China. 4. John Van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, NG11 8NS, United Kingdom.
Abstract
OBJECTIVE: To analyze the mutations in transcription regulatory sequences (TRSs) of coronaviruss (CoV) to provide the basis for exploring the patterns of SARS-CoV-2 transmission and outbreak. METHODS: A combined evolutionary and molecular functional analysis of all sets of publicly available genomic data of viruses was performed. RESULTS: A leader transcription regulatory sequence (TRS-L) usually comprises the first 60-70 nts of the 5' UTR in a CoV genome, and the body transcription regulatory sequences (TRS-Bs) are located immediately upstream of the genes other than ORF1a and 1b. In each CoV genome, the TRS-L and TRS-Bs share a specific consensus sequence, namely the TRS motif. Any changes of nucleotide residues in the TRS motifs are defined as TRS motif mutations. Mutations in the TRS-L or multiple TRS-Bs result in superattenuated variants. The spread of super-attenuated variants may cause an increase in asymptomatic or mild infections, prolonged incubation periods and a decreased detection rate of the viruses, thus posing new challenges to SARS-CoV-2 prevention and control. The super-attenuated variants also increase their possibility of long-term coexistence with humans. The Delta variant is significantly different from all the previous variants and may lead to a large-scale transmission. The Delta variant (B.1.617.2) with TRS motif mutation has already appeared and shown signs of spreading in Singapore, which, and even the Southeast Asia, may become the new epicenter of the next wave of SARS-CoV-2 outbreak. CONCLUSION: TRS motif mutation will occur in all variants of SARS-CoV-2 and may result in super-attenuated variants. Only super-attenuated variants with TRS motif mutations will eventually lose the abilities of cross-species transmission and causing outbreaks.
OBJECTIVE: To analyze the mutations in transcription regulatory sequences (TRSs) of coronaviruss (CoV) to provide the basis for exploring the patterns of SARS-CoV-2 transmission and outbreak. METHODS: A combined evolutionary and molecular functional analysis of all sets of publicly available genomic data of viruses was performed. RESULTS: A leader transcription regulatory sequence (TRS-L) usually comprises the first 60-70 nts of the 5' UTR in a CoV genome, and the body transcription regulatory sequences (TRS-Bs) are located immediately upstream of the genes other than ORF1a and 1b. In each CoV genome, the TRS-L and TRS-Bs share a specific consensus sequence, namely the TRS motif. Any changes of nucleotide residues in the TRS motifs are defined as TRS motif mutations. Mutations in the TRS-L or multiple TRS-Bs result in superattenuated variants. The spread of super-attenuated variants may cause an increase in asymptomatic or mild infections, prolonged incubation periods and a decreased detection rate of the viruses, thus posing new challenges to SARS-CoV-2 prevention and control. The super-attenuated variants also increase their possibility of long-term coexistence with humans. The Delta variant is significantly different from all the previous variants and may lead to a large-scale transmission. The Delta variant (B.1.617.2) with TRS motif mutation has already appeared and shown signs of spreading in Singapore, which, and even the Southeast Asia, may become the new epicenter of the next wave of SARS-CoV-2 outbreak. CONCLUSION: TRS motif mutation will occur in all variants of SARS-CoV-2 and may result in super-attenuated variants. Only super-attenuated variants with TRS motif mutations will eventually lose the abilities of cross-species transmission and causing outbreaks.
Authors: Raquel Viana; Sikhulile Moyo; Daniel G Amoako; Houriiyah Tegally; Cathrine Scheepers; Christian L Althaus; Ugochukwu J Anyaneji; Phillip A Bester; Maciej F Boni; Mohammed Chand; Wonderful T Choga; Rachel Colquhoun; Michaela Davids; Koen Deforche; Deelan Doolabh; Louis du Plessis; Susan Engelbrecht; Josie Everatt; Jennifer Giandhari; Marta Giovanetti; Diana Hardie; Verity Hill; Nei-Yuan Hsiao; Arash Iranzadeh; Arshad Ismail; Charity Joseph; Rageema Joseph; Legodile Koopile; Sergei L Kosakovsky Pond; Moritz U G Kraemer; Lesego Kuate-Lere; Oluwakemi Laguda-Akingba; Onalethatha Lesetedi-Mafoko; Richard J Lessells; Shahin Lockman; Alexander G Lucaci; Arisha Maharaj; Boitshoko Mahlangu; Tongai Maponga; Kamela Mahlakwane; Zinhle Makatini; Gert Marais; Dorcas Maruapula; Kereng Masupu; Mogomotsi Matshaba; Simnikiwe Mayaphi; Nokuzola Mbhele; Mpaphi B Mbulawa; Adriano Mendes; Koleka Mlisana; Anele Mnguni; Thabo Mohale; Monika Moir; Kgomotso Moruisi; Mosepele Mosepele; Gerald Motsatsi; Modisa S Motswaledi; Thongbotho Mphoyakgosi; Nokukhanya Msomi; Peter N Mwangi; Yeshnee Naidoo; Noxolo Ntuli; Martin Nyaga; Lucier Olubayo; Sureshnee Pillay; Botshelo Radibe; Yajna Ramphal; Upasana Ramphal; James E San; Lesley Scott; Roger Shapiro; Lavanya Singh; Pamela Smith-Lawrence; Wendy Stevens; Amy Strydom; Kathleen Subramoney; Naume Tebeila; Derek Tshiabuila; Joseph Tsui; Stephanie van Wyk; Steven Weaver; Constantinos K Wibmer; Eduan Wilkinson; Nicole Wolter; Alexander E Zarebski; Boitumelo Zuze; Dominique Goedhals; Wolfgang Preiser; Florette Treurnicht; Marietje Venter; Carolyn Williamson; Oliver G Pybus; Jinal Bhiman; Allison Glass; Darren P Martin; Andrew Rambaut; Simani Gaseitsiwe; Anne von Gottberg; Tulio de Oliveira Journal: Nature Date: 2022-01-07 Impact factor: 49.962