Coincident rapid expansion of two SARS-CoV-2 lineages with enhanced infectivity in Nigeria

Egon A Ozer, Lacy M Simons, Olubusuyi M Adewumi, Adeola A Fowotade, Ewean C Omoruyi, Johnson A Adeniji, Taylor J Dean, Janet Zayas, Pavan P Bhimalli, Michelle K Ash, Adam Godzik, Jeffrey R Schneider, João I Mamede, Babafemi O Taiwo, Judd F Hultquist, Ramon Lorenzo-Redondo, Egon A Ozer, Lacy M Simons, Olubusuyi M Adewumi, Adeola A Fowotade, Ewean C Omoruyi, Johnson A Adeniji, Taylor J Dean, Janet Zayas, Pavan P Bhimalli, Michelle K Ash, Adam Godzik, Jeffrey R Schneider, João I Mamede, Babafemi O Taiwo, Judd F Hultquist, Ramon Lorenzo-Redondo

Abstract

The emergence of new SARS-CoV-2 variants with enhanced transmissibility or decreased susceptibility to immune responses is a major threat to global efforts to end the coronavirus disease 2019 (COVID-19) pandemic. Disparities in viral genomic surveillance capabilities and efforts have resulted in gaps in our understanding of the viral population dynamics across the globe. Nigeria, despite having the largest population of any nation in Africa, has had relatively little SARS-CoV-2 sequence data made publicly available. Here we report the whole-genome sequences of 74 SARS-CoV-2 isolates collected from individuals in Oyo State, Nigeria in January 2021. Most isolates belonged to either the B.1.1.7 Alpha "variant of concern" or the B.1.525 Eta lineage, which is currently considered a "variant of interest" containing multiple spike protein mutations previously associated with enhanced transmissibility and possible immune escape. Nigeria has the highest reported frequency of the B.1.525 lineage globally with phylogenetic characteristics consistent with a recent monophyletic origin and rapid expansion. Spike protein from the B.1.525 lineage displayed both increased infectivity and decreased neutralization by convalescent sera compared to Spike proteins from other clades. These results, along with indications that the virus is outpacing the B.1.1.7 lineage in Nigeria, suggest that the B.1.525 lineage represents another "variant of concern" and further underline the importance of genomic surveillance in undersampled regions across the globe.

Keywords: B.1.1.7; B.1.525; COVID-19; Global health; Lineage; Phylogenetics; SARS-CoV-2; Variant of concern; Whole genome sequencing.

Conflict of interest statement

CONFLICTS OF INTEREST None.

Figures

Figure 1.. Phylogenetic analysis of SARS-CoV-2 isolates…
Figure 1.. Phylogenetic analysis of SARS-CoV-2 isolates in Oyo state.
a) ML phylogenetic tree of 74 SARS-CoV-2 specimen genomes in Oyo state collected between January 2 and January 14, 2021. All non-zero statistical support values for each branch are indicated. Lineages of interest are indicated and colored. Midpoint rooting was used for representation purposes. b) Distribution of the different pangolin lineages found in the Oyo dataset reported here.
Figure 2.. Phylogenetic analysis of Nigerian sequences…
Figure 2.. Phylogenetic analysis of Nigerian sequences compared to the global pandemic.
ML phylogenetic temporal reconstruction of full genome sequences from Nigeria and 4000 randomly sampled global sequences from GISAID as of February 14th, 2021. Clades corresponding to B.1.1.7 and B.1.525 lineages are indicated. Branches and tips are colored by country.
Figure 3.. Phylodynamic tree of the entire…
Figure 3.. Phylodynamic tree of the entire B.1.525 lineage.
Maximum clade credibility tree where branch colors represent the most probable geographical location of their descendent node inferred through Bayesian reconstruction of the ancestral state. All full genome B.1.525 sequences from this study and from GISAID as of February 14th, 2021 were included in the analysis. We included two B.1 lineage sequences from Nigeria and 10 randomly sampled from GISAID to help root the phylogenies. The branch that leads to the node that represents the B.1.525 MRCA is indicated. The width of the node circles represents their posterior probability.
Figure 4.. Analysis of B.1.525 Spike mutations…
Figure 4.. Analysis of B.1.525 Spike mutations on cellular entry and antibody neutralization.
a) Overall structure of the SARS-CoV-2 spike protein trimer with N-terminal domains (NTD) in blue, receptor binding domains (RBD) in magenta, and ACE2 receptor in dark grey, based on the set of PDB coordinates 7a94 showing the spike protein bound to one ACE2 molecule. Mutated residues in the B.1.525 spike are shown in chain A as red spheres, deleted residues as black spheres. A model of the B.1.525 NTD in the inset is shown interacting with the Fab C25 antibody (PDB 7m8j). The unmodified chain on the wild type NTD is shown in orange. A significant conformational change in the N3 loop results in a significant drop in the (estimated) binding energy to this antibody, from −10.8 kcal/mol to −1.3. b) Nanoluc activity measured in relative light units (RLU) ratio between each of the mutants tested and the D614G mutant. D614G was used to calculate the ratios due to its predominance in the population before the appearance of the B.1.1.7 and B.1.525 lineages. Values are shown for each of the dilutions used after p24 concentration normalization. Bars represent the mean and lines represent the standard deviation of the replicates. c) Neutralization EC50 comparison between the different Spikes tested in the presence of sera from vaccinated (Pfizer or Moderna groups) or naturally-infected (Nigeria group) individuals. EC50 values were estimated using a four-parameter log-logistic function either with the NTD or RBD antibody concentrations. Statistically significant FDR values are indicated for within mutant comparisons (ns indicates non-significant FDR).
Figure 5.. Daily SARS-CoV2 Incidence in Nigeria.
Figure 5.. Daily SARS-CoV2 Incidence in Nigeria.
Confirmed new cases in Nigeria obtained from Johns Hopkins University Coronavirus resource center (https://coronavirus.jhu.edu/). The TMRCA (solid line) and 95% High Probability Density (HPD) (dashed lines) in Nigeria of B.1.1.7 and B.1.525 lineages estimated using Bayesian methods is indicated.

References

    1. Wang C., Horby P.W., Hayden F.G. & Gao G.F. A novel coronavirus outbreak of global health concern. Lancet 395, 470–473 (2020).
    1. Zhu N., et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med 382, 727–733 (2020).
    1. Zhou P., et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579, 270–273 (2020).
    1. van Dorp L., et al. Emergence of genomic diversity and recurrent mutations in SARS-CoV-2. Infect Genet Evol 83, 104351 (2020).
    1. Li X., et al. Transmission dynamics and evolutionary history of 2019-nCoV. J Med Virol 92, 501–511 (2020).
    1. Meredith L.W., et al. Rapid implementation of SARS-CoV-2 sequencing to investigate cases of healthcare associated COVID-19: a prospective genomic surveillance study. Lancet Infect Dis 20, 1263–1271 (2020).
    1. Dearlove B., et al. A SARS-CoV-2 vaccine candidate would likely match all currently circulating variants. Proc Natl Acad Sci U S A 117, 23652–23662 (2020).
    1. Lu J., et al. Genomic Epidemiology of SARS-CoV-2 in Guangdong Province, China. Cell 181, 997–1003 e1009 (2020).
    1. Gonzalez-Reiche A.S., et al. Introductions and early spread of SARS-CoV-2 in the New York City area. Science 369, 297–301 (2020).
    1. Lorenzo-Redondo R., et al. A clade of SARS-CoV-2 viruses associated with lower viral loads in patient upper airways. EBioMedicine 62, 103112 (2020).
    1. Korber B., et al. Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus. Cell 182, 812–827 e819 (2020).
    1. Hou Y.J., et al. SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo. Science 370, 1464–1468 (2020).
    1. Li Q., et al. The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity. Cell 182, 1284–1294 e1289 (2020).
    1. Volz E., et al. Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity. Cell 184, 64–75 e11 (2021).
    1. Plante J.A., et al. Spike mutation D614G alters SARS-CoV-2 fitness. Nature (2020).
    1. (CDC), C.f.D.C.a.P. SARS-CoV-2 Variant Classifications and Definitions. (2021).
    1. Tegally H., et al. Sixteen novel lineages of SARS-CoV-2 in South Africa. Nat Med (2021).
    1. Leung K., Shum M.H., Leung G.M., Lam T.T. & Wu J.T. Early transmissibility assessment of the N501Y mutant strains of SARS-CoV-2 in the United Kingdom, October to November 2020. Euro Surveill 26(2021).
    1. Volz E., et al. Transmission of SARS-CoV-2 Lineage B.1.1.7 in England: Insights from linking epidemiological and genetic data. medRxiv, 2020.2012.2030.20249034 (2021).
    1. Rambaut A., et al. Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage in the UK defined by a novel set of spike mutations. (Dec 18, 2020).
    1. Rambaut A., et al. A dynamic nomenclature proposal for SARS-CoV-2 lineages to assist genomic epidemiology. Nat Microbiol (2020).
    1. Faria N.R., et al. Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil. Science 372, 815–821 (2021).
    1. Lauring A.S. & Hodcroft E.B. Genetic Variants of SARS-CoV-2-What Do They Mean? JAMA 325, 529–531 (2021).
    1. Grubaugh N.D., Hodcroft E.B., Fauver J.R., Phelan A.L. & Cevik M. Public health actions to control new SARS-CoV-2 variants. Cell 184, 1127–1132 (2021).
    1. Davies N.G., et al. Estimated transmissibility and severity of novel SARS-CoV-2 Variant of Concern 202012/01 in England. medRxiv, 2020.2012.2024.20248822 (2020).
    1. Edara V.V., et al. Reduced binding and neutralization of infection- and vaccine-induced antibodies to the B.1.351 (South African) SARS-CoV-2 variant. bioRxiv (2021).
    1. Xie X., et al. Neutralization of SARS-CoV-2 spike 69/70 deletion, E484K and N501Y variants by BNT162b2 vaccine-elicited sera. Nat Med (2021).
    1. Wang L., et al. Antibodies with potent and broad neutralizing activity against antigenically diverse and highly transmissible SARS-CoV-2 variants. bioRxiv (2021).
    1. Administration, U.S.F.a.D. FDA authorizes revisions to fact sheets to address SARS-CoV-2 variants for monoclonal antibody products under emergency use authorization. (2021).
    1. Konings F., et al. SARS-CoV-2 Variants of Interest and Concern naming scheme conducive for global discourse. Nat Microbiol (2021).
    1. Lemey P., et al. Accommodating individual travel history and unsampled diversity in Bayesian phylogeographic inference of SARS-CoV-2. Nat Commun 11, 5110 (2020).
    1. Lu L., Lycett S., Ashworth J., Mutapi F. & Woolhouse M. What are SARS-CoV-2 genomes from the WHO Africa region member states telling us? BMJ Glob Health 6(2021).
    1. Inzaule S.C., Tessema S.K., Kebede Y., Ogwell Ouma A.E. & Nkengasong J.N. Genomic-informed pathogen surveillance in Africa: opportunities and challenges. Lancet Infect Dis (2021).
    1. (CDC), C.f.D.C.a.P. CDC 2019-Novel Coronavirus (2019-nCoV) Real Time RT-PCR Diagnostic Panel. (2020).
    1. Quick J., et al. Multiplex PCR method for MinION and Illumina sequencing of Zika and other virus genomes directly from clinical samples. Nat Protoc 12, 1261–1276 (2017).
    1. Quick J. nCoV-2019 sequencing protocol v2 (GunIt).
    1. Elbe S. & Buckland-Merrett G. Data, disease and diplomacy: GISAID’s innovative contribution to global health. Glob Chall 1, 33–46 (2017).
    1. Shu Y. & McCauley J. GISAID: Global initiative on sharing all influenza data - from vision to reality. Euro Surveill 22(2017).
    1. Nigeria Cenre for Disease Control. NCDC Coronavirus COVID-19 Microsite.
    1. O’Toole Á. & Hill V. Global Report of B.1.525 lineage. (2021).
    1. Frampton D., et al. Genomic characteristics and clinical effect of the emergent SARS-CoV-2 B.1.1.7 lineage in London, UK: a whole-genome sequencing and hospital-based cohort study. Lancet Infect Dis (2021).
    1. Meng B., et al. Recurrent emergence of SARS-CoV-2 spike deletion H69/V70 and its role in the variant of concern lineage B.1.1.7. Cell Reports, 109292 (2021).
    1. Collier D.A., et al. Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies. Nature 593, 136–141 (2021).
    1. Cerutti G., et al. Potent SARS-CoV-2 neutralizing antibodies directed against spike N-terminal domain target a single supersite. Cell Host Microbe 29, 819–833 e817 (2021).
    1. Liu L., et al. Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike. Nature 584, 450–456 (2020).
    1. Rogers T.F., et al. Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model. Science 369, 956–963 (2020).
    1. Xia S., et al. The role of furin cleavage site in SARS-CoV-2 spike protein-mediated membrane fusion in the presence or absence of trypsin. Signal Transduct Target Ther 5, 92 (2020).
    1. Harvey W.T., et al. SARS-CoV-2 variants, spike mutations and immune escape. Nat Rev Microbiol (2021).
    1. McCarthy K.R., et al. Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape. Science 371, 1139–1142 (2021).
    1. Xie X., et al. Neutralization of N501Y mutant SARS-CoV-2 by BNT162b2 vaccine-elicited sera. bioRxiv, 2021.2001.2007.425740 (2021).
    1. Galloway S.E., et al. Emergence of SARS-CoV-2 B.1.1.7 Lineage — United States, December 29, 2020–January 12, 2021. Morbidity and Mortality Weekly Report 70, 95–99 (2021).
    1. Public Health England. Investigation of novel SARS-CoV-2 variant: Variant of Concern 202012/01, Technical Briefing 3. (London, United Kingdom: 2021).
    1. Wu K., et al. mRNA-1273 vaccine induces neutralizing antibodies against spike mutants from global SARS-CoV-2 variants. bioRxiv, 2021.2001.2025.427948 (2021).
    1. Wang Z., et al. mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. bioRxiv, 2021.2001.2015.426911 (2021).
    1. Wibmer C.K., et al. SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma. bioRxiv, 2021.2001.2018.427166 (2021).
    1. Weisblum Y., et al. Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. Elife 9(2020).
    1. Zhou D., et al. Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine induced sera. in Cell (Elsevier, 2021).
    1. Greaney A.J., et al. Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies. Cell Host Microbe 29, 463–476 e466 (2021).
    1. Bo Meng S.A.K., Papa Guido, Datir Rawlings, Ferreira Isabella ATM., Marelli Sara, Harvey William T., Lytras Spyros, Mohamed Ahmed, Gallo Giulia, Thakur Nazia, Collier Dami A., Mlcochova Petra, Duncan Lidia M., Carabelli Alessandro M., Kenyon Julia C., Lever Andrew M., De Marco Anna, Saliba Christian, Culap Katja, Cameroni Elisabetta, Matheson Nicholas J., Piccoli Luca, Corti Davide, James Leo C., Robertson David L., Bailey Dalan, Gupta Ravindra K.. Recurrent emergence of SARS-CoV-2 spike deletion H69/V70 and its role in the variant of concern lineage B.1.1.7. Cell Reports (2021).
    1. Andreano E., et al. SARS-CoV-2 escape in vitro from a highly neutralizing COVID-19 convalescent plasma. bioRxiv (2020).
    1. Baum A., et al. Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science 369, 1014–1018 (2020).
    1. Liu Z., et al. Identification of SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization. Cell Host Microbe 29, 477–488 e474 (2021).
    1. Suryadevara N., et al. Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein. Cell 184, 2316–2331 e2315 (2021).
    1. McCallum M., et al. N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2. Cell 184, 2332–2347 e2316 (2021).
    1. Lok S.M. An NTD supersite of attack. Cell Host Microbe 29, 744–746 (2021).
    1. Grubaugh N.D., et al. An amplicon-based sequencing framework for accurately measuring intrahost virus diversity using PrimalSeq and iVar. Genome Biol 20, 8 (2019).
    1. Katoh K. & Standley D.M. MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol Biol Evol 30, 772–780 (2013).
    1. Kumar S., Stecher G., Li M., Knyaz C. & Tamura K. MEGA X: Molecular Evolutionary Genetics Analysis across Computing Platforms. Mol Biol Evol 35, 1547–1549 (2018).
    1. Minh B.Q., et al. IQ-TREE 2: New Models and Efficient Methods for Phylogenetic Inference in the Genomic Era. Mol Biol Evol 37, 1530–1534 (2020).
    1. Kalyaanamoorthy S., Minh B.Q., Wong T.K.F., von Haeseler A. & Jermiin L.S. ModelFinder: fast model selection for accurate phylogenetic estimates. Nat Methods 14, 587–589 (2017).
    1. Anisimova M. & Gascuel O. Approximate likelihood-ratio test for branches: A fast, accurate, and powerful alternative. Syst Biol 55, 539–552 (2006).
    1. Hoang D.T., Chernomor O., von Haeseler A., Minh B.Q. & Vinh L.S. UFBoot2: Improving the Ultrafast Bootstrap Approximation. Mol Biol Evol 35, 518–522 (2018).
    1. Sagulenko P., Puller V. & Neher R.A. TreeTime: Maximum-likelihood phylodynamic analysis. Virus Evol 4, vex042 (2018).
    1. Bouckaert R., et al. BEAST 2.5: An advanced software platform for Bayesian evolutionary analysis. PLoS Comput Biol 15, e1006650 (2019).
    1. Mamede J.I., Sitbon M., Battini J.L. & Courgnaud V. Heterogeneous susceptibility of circulating SIV isolate capsids to HIV-interacting factors. Retrovirology 10, 77 (2013).
    1. Waterhouse A., et al. SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res 46, W296–W303 (2018).
    1. Voss W.N., et al. Prevalent, protective, and convergent IgG recognition of SARS-CoV-2 non-RBD spike epitopes. Science (2021).
    1. Huang X., Pearce R. & Zhang Y. EvoEF2: accurate and fast energy function for computational protein design. Bioinformatics 36, 1135–1142 (2020).
    1. Pearce R., Huang X., Setiawan D. & Zhang Y. EvoDesign: Designing Protein-Protein Binding Interactions Using Evolutionary Interface Profiles in Conjunction with an Optimized Physical Energy Function. J Mol Biol 431, 2467–2476 (2019).
    1. Benton D.J., et al. Receptor binding and priming of the spike protein of SARS-CoV-2 for membrane fusion. Nature 588, 327–330 (2020).

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir