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In situ single-cell profiling sheds light on IFI27 localisation during SARS-CoV-2 infection.

ABSTRACT: The utilization of single-cell resolved spatial transcriptomics to delineate immune responses during SARS-CoV-2 infection was able to identify M1 macrophages to have elevated expression of IFI27 in areas of infection.

SUBMITTER: Tan CW

PROVIDER: S-EPMC10884333 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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In situ single-cell profiling sheds light on IFI27 localisation during SARS-CoV-2 infection.

Tan Chin Wee CW Chen Jinjin J Liu Ning N Bhuva Dharmesh D DD Blick Tony T Monkman James J Cooper Caroline C Kharbanda Malvika M Feher Kristen K Phipson Belinda B Killingbeck Emily E EE Pan Liuliu L Kim Youngmi Y Liang Yan Y Nam Andy A Leon Michael M Souza-Fonseca-Guimaraes Paulo P Nagashima Seigo S Camargo Martins Ana Paula AP Machado-Souza Cleber C de Noronha Lucia L Tang Benjamin B Short Kirsty K Fraser John J Belz Gabrielle T GT Souza-Fonseca-Guimaraes Fernando F Kulasinghe Arutha A Davis Melissa J MJ

EBioMedicine 20240219

The utilization of single-cell resolved spatial transcriptomics to delineate immune responses during SARS-CoV-2 infection was able to identify M1 macrophages to have elevated expression of IFI27 in areas of infection. ...[more]

PMID: 38377798

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In situ single-cell profiling sheds light on IFI27 localisation during SARS-CoV-2 infection

Project description:The utilization of single-cell resolved spatial transcriptomics to delineate immune responses during SARS-CoV-2 infection was able to identify macrophages to have elevated expression of IFI27 in areas of infection.

2024-01-28 | GSE253474 | GEO

In situ single-cell profiling sheds light on IFI27 localisation during SARS-CoV-2 infection

Project description:In situ single-cell profiling sheds light on IFI27 localisation during SARS-CoV-2 infection

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Project description:Bat sarbecovirus BANAL-236 is highly related to SARS-CoV-2 and infects human cells, albeit lacking the furin cleavage site in its spike protein. BANAL-236 replicates efficiently and pauci-symptomatically in humanized mice and in macaques, where its tropism is enteric, strongly differing from that of SARS-CoV-2. BANAL-236 infection leads to protection against superinfection by a virulent strain. We find no evidence of antibodies recognizing bat sarbecoviruses in populations in close contact with bats in which the virus was identified, indicating that such spillover infections, if they occur, are rare. Six passages in humanized mice or in human intestinal cells, mimicking putative early spillover events, select adaptive mutations without appearance of a furin cleavage site and no change in virulence. Therefore, acquisition of a furin site in the spike protein is likely a pre-spillover event that did not occur upon replication of a SARS-CoV-2-like bat virus in humans or other animals. Other hypotheses regarding the origin of the SARS-CoV-2 should therefore be evaluated, including the presence of sarbecoviruses carrying a spike with a furin cleavage site in bats.

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The IFN-induced protein IFI27 binds MDA5 and counteracts its activation after SARS-CoV-2 infection.

Project description:Innate immune responses are induced after viral infections, being these responses essential to establish an antiviral response in the host. The RIG-I-like receptors (RLRs), RIG-I and MDA5 are pivotal for virus detection by recognizing viral RNAs in the cytoplasm of infected cells, initiating these responses. However, since excessive responses can have a negative effect on the host, regulatory feedback mechanisms are needed. In this work, we describe that IFN alpha-inducible protein 27 (IFI27) co-immunoprecipitates with melanoma differentiation-associated protein 5 (MDA5), being this interaction likely mediated by RNAs. In addition, by using IFI27 overexpression, knock-out, and knock-down cells, we show that IFI27 inhibits MDA5 oligomerization and activation, counteracting the innate immune responses induced after SARS-CoV-2 infections or after polyinosinic-polycytidylic acid (poly(I:C)) transfection. Furthermore, our data indicate that IFI27 competes with MDA5 for poly(I:C) binding, providing a likely explanation for the effect of IFI27 in inhibiting MDA5 activation. This new function of IFI27 could be used to design target-driven compounds to treat diseases associated with an exacerbated induction of innate immune responses, such as those induced by SARS-CoV-2.

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Recovery of Deleted Deep Sequencing Data Sheds More Light on the Early Wuhan SARS-CoV-2 Epidemic.

Project description:The origin and early spread of SARS-CoV-2 remains shrouded in mystery. Here, I identify a data set containing SARS-CoV-2 sequences from early in the Wuhan epidemic that has been deleted from the NIH's Sequence Read Archive. I recover the deleted files from the Google Cloud and reconstruct partial sequences of 13 early epidemic viruses. Phylogenetic analysis of these sequences in the context of carefully annotated existing data further supports the idea that the Huanan Seafood Market sequences are not fully representative of the viruses in Wuhan early in the epidemic. Instead, the progenitor of currently known SARS-CoV-2 sequences likely contained three mutations relative to the market viruses that made it more similar to SARS-CoV-2's bat coronavirus relatives.

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SHAE002: SARS-CoV, SARS-dORF6 and SARS-BatSRBD infection of HAE cultures.

Project description:HAE cultures were infected with SARS-CoV, SARS-dORF6 or SARS-BatSRBD and were directly compared to A/CA/04/2009 H1N1 influenza-infected cultures. Cell samples were collected at various hours post-infection for analysis. Time Points = 0, 12, 24, 36, 48, 60, 72, 84 and 96 hrs post-infection for SARS-CoV, SARS-dORF6 and SARS-BatSRBD. Time Points = 0, 6, 12, 18, 24, 36 and 48 hrs post-infection for H1N1. Done in triplicate or quadruplicate for RNA Triplicates/quadruplicates are defined as 3/4 different wells, plated at the same time and using the same cell stock for all replicates. Time matched mocks done in triplicate from same cell stock as rest of samples. Culture medium (the same as what the virus stock is in) will be used for the mock infections. Infection was done at an MOI of 2.

2013-07-31 | E-GEOD-47960 | biostudies-arrayexpress

SHAE003: SARS-CoV, SARS-dORF6 and SARS-BatSRBD infection of HAE cultures.

Project description:HAE cultures were infected with SARS-CoV, SARS-ddORF6 or SARS-BatSRBD and were directly compared to A/CA/04/2009 H1N1 influenza-infected cultures. Cell samples were collected at various hours post-infection for analysis. Time Points = 0, 12, 24, 36, 48, 60, 72, 84 and 96 hrs post-infection for SARS-CoV. Time Points = 0, 24, 48, 60, 72, 84 and 96 hrs post-infection forSARS-ddORF6 and SARS-BatSRBD. Time Points = 0, 6, 12, 18, 24, 36 and 48 hrs post-infection for H1N1. Done in triplicate/quadruplicate for RNA Triplicates/quadruplicates are defined as 3/4 different wells, plated at the same time and using the same cell stock for all replicates. Time matched mocks done in triplicate from same cell stock as rest of samples. Culture medium (the same as what the virus stock is in) will be used for the mock infections. Infection was done at an MOI of 2.

2013-07-31 | E-GEOD-47961 | biostudies-arrayexpress

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