Background: Wildtype mice are not susceptible to SARS-CoV-2 infection. Emerging SARS-CoV-2 variants, including B.1.1.7, B.1.351, P.1, and P.3, contain mutations in spike that has been suggested to associate with an increased recognition of mouse ACE2, raising the postulation that these SARS-CoV-2 variants may have evolved to expand species tropism to wildtype mouse and potentially other murines. Our study evaluated this possibility with substantial public health importance.
Methods: We investigated the capacity of wildtype (WT) SARS-CoV-2 and SARS-CoV-2 variants in infecting mice (Mus musculus) and rats (Rattus norvegicus) under in vitro and in vivo settings. Susceptibility to infection was evaluated with RT-qPCR, plaque assays, immunohistological stainings, and neutralization assays.
Findings: Our results reveal that B.1.1.7 and other N501Y-carrying variants but not WT SARS-CoV-2 can infect wildtype mice. High viral genome copies and high infectious virus particle titres are recovered from the nasal turbinate and lung of B.1.1.7-inocluated mice for 4-to-7 days post infection. In agreement with these observations, robust expression of viral nucleocapsid protein and histopathological changes are detected from the nasal turbinate and lung of B.1.1.7-inocluated mice but not that of the WT SARS-CoV-2-inoculated mice. Similarly, B.1.1.7 readily infects wildtype rats with production of infectious virus particles.
Interpretation: Our study provides direct evidence that the SARS-CoV-2 variant, B.1.1.7, as well as other N501Y-carrying variants including B.1.351 and P.3, has gained the capability to expand species tropism to murines and public health measures including stringent murine control should be implemented to facilitate the control of the ongoing pandemic.
Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.
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http://dx.doi.org/10.1016/j.ebiom.2021.103643 | DOI Listing |
Sci Rep
December 2024
Department of Anatomy, Faculty of Science, Mahidol University, 272 Rama VI Road, Ratchathewi, Bangkok, 10400, Thailand.
SARS-CoV-2, the cause of COVID-19, primarily targets lung tissue, leading to pneumonia and lung injury. The spike protein of this virus binds to the common receptor on susceptible tissues and cells called the angiotensin-converting enzyme-2 (ACE2) of the angiotensin (ANG) system. In this study, we produced chimeric Macrobrachium rosenbergii nodavirus virus-like particles, presenting a short peptide ligand (ACE2tp), based on angiotensin-II (ANG II), on their outer surfaces to allow them to specifically bind to ACE2-overexpressing cells called ACE2tp-MrNV-VLPs.
View Article and Find Full Text PDFBMC Infect Dis
December 2024
KEMRI-Wellcome Trust Research Programme, P.O. Box 230, Kilifi, Kenya.
Increased immune evasion by emerging and highly mutated SARS-CoV-2 variants is a key challenge to the control of COVID-19. The majority of these mutations mainly target the spike protein, allowing the new variants to escape the immunity previously raised by vaccination and/or infection by earlier variants of SARS-CoV-2. In this study, we investigated the neutralizing capacity of antibodies against emerging variants of interest circulating between May 2023 and October 2024 using sera from representative samples of the Kenyan population.
View Article and Find Full Text PDFVirology
December 2024
Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), Departamento de Biotecnología y Bioingeniería, Av. Instituto Politécnico Nacional 2508, Mexico City, 07360, Mexico; CINVESTAV, Programa de Doctorado Transdisciplinario en Desarrollo Científico y Tecnológico para la Sociedad, Mexico. Electronic address:
COVID-19 infections continue due to accessibility barriers to vaccines and the emergence of SARS-CoV-2 variants. An effective, safe, accessible, and broad-spectrum vaccine is still needed to control the disease. We developed a multivalent protein subunit vaccine comprising antigens designed from a non-N-glycosylated region of the receptor-binding domain of the spike protein of SARS-CoV-2.
View Article and Find Full Text PDFImmunol Rev
December 2024
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA.
The SARS-CoV-2 spike (S) protein has undergone significant evolution, enhancing both receptor binding and immune evasion. In this review, we summarize ongoing efforts to develop antibodies targeting various epitopes of the S protein, focusing on their neutralization potency, breadth, and escape mechanisms. Antibodies targeting the receptor-binding site (RBS) typically exhibit high neutralizing potency but are frequently evaded by mutations in SARS-CoV-2 variants.
View Article and Find Full Text PDFEmerg Microbes Infect
December 2024
Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan 650000, China.
Preventing immune escape of SARS-CoV-2 variants is crucial in vaccine development to ensure broad protection against the virus. Conformational epitopes beyond the RBD region are vital components of the spike protein but have received limited attention in the development of broadly protective SARS-CoV-2 vaccines. In this study, we used a DNA prime-protein boost regimen to evaluate the broad cross-neutralization potential of immune response targeting conformational non-RBD region against SARS-CoV-2 viruses in mice.
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