Multiorgan and Renal Tropism of SARS-CoV-2.
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ABSTRACT:
SUBMITTER: Puelles VG
PROVIDER: S-EPMC7240771 | biostudies-literature | 2020 Aug
REPOSITORIES: biostudies-literature
Publications
Multiorgan and Renal Tropism of SARS-CoV-2.
Puelles Victor G VG Lütgehetmann Marc M Lindenmeyer Maja T MT Sperhake Jan P JP Wong Milagros N MN Allweiss Lena L Chilla Silvia S Heinemann Axel A Wanner Nicola N Liu Shuya S Braun Fabian F Lu Shun S Pfefferle Susanne S Schröder Ann S AS Edler Carolin C Gross Oliver O Glatzel Markus M Wichmann Dominic D Wiech Thorsten T Kluge Stefan S Pueschel Klaus K Aepfelbacher Martin M Huber Tobias B TB
The New England journal of medicine 20200513 6
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Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), has led to an unprecedented public health emergency worldwide. While common cold symptoms are observed in mild cases, COVID-19 is accompanied by multiorgan failure in severe patients. Organ damage in COVID-19 patients is partially associated with the indirect effects of SARS-CoV-2 infection (e.g., systemic inflammation, hypoxic-ischemic damage, coagulopathy), but early processes in COVID-19 patients that trigger a chain of indirect effects are connected with the direct infection of cells by the virus. To understand the virus transmission routes and the reasons for the wide-spectrum of complications and severe outcomes of COVID-19, it is important to identify the cells targeted by SARS-CoV-2. This review summarizes the major steps of investigation and the most recent findings regarding SARS-CoV-2 cellular tropism and the possible connection between the early stages of infection and multiorgan failure in COVID-19. The SARS-CoV-2 pandemic is the first epidemic in which data extracted from single-cell RNA-seq (scRNA-seq) gene expression data sets have been widely used to predict cellular tropism. The analysis presented here indicates that the SARS-CoV-2 cellular tropism predictions are accurate enough for estimating the potential susceptibility of different cells to SARS-CoV-2 infection; however, it appears that not all susceptible cells may be infected in patients with COVID-19.
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Project description:BackgroundHuman spillovers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to dogs and the emergence of a highly contagious avian-origin H3N2 canine influenza virus have raised concerns on the role of dogs in the spread of SARS-CoV-2 and their susceptibility to existing human and avian influenza viruses, which might result in further reassortment.MethodsWe systematically studied the replication kinetics of SARS-CoV-2, SARS-CoV, influenza A viruses of H1, H3, H5, H7, and H9 subtypes, and influenza B viruses of Yamagata-like and Victoria-like lineages in ex vivo canine nasal cavity, soft palate, trachea, and lung tissue explant cultures and examined ACE2 and sialic acid (SA) receptor distribution in these tissues.ResultsThere was limited productive replication of SARS-CoV-2 in canine nasal cavity and SARS-CoV in canine nasal cavity, soft palate, and lung, with unexpectedly high ACE2 levels in canine nasal cavity and soft palate. Canine tissues were susceptible to a wide range of human and avian influenza viruses, which matched with the abundance of both human and avian SA receptors.ConclusionsExistence of suitable receptors and tropism for the same tissue foster virus adaptation and reassortment. Continuous surveillance in dog populations should be conducted given the many chances for spillover during outbreaks.
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Project description:BackgroundWildtype 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.MethodsWe 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.FindingsOur 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.InterpretationOur 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.FundingA full list of funding bodies that contributed to this study can be found in the Acknowledgements section.
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