Biology subjects

Moreira, E. A.

Publications and source records attributed to Moreira, E. A..

4 recordsLinked to original sources

bioRxiv2026

Bovine-derived influenza A virus (H5N1) shows efficient replication in well-differentiated human nasal epithelial cells without requiring genetic adaptation

Highly pathogenic avian influenza (H5N1) viruses of clade 2.3.4.4b have caused significant losses among bird populations worldwide and have repeatedly crossed the species barrier, infecting mammals, including humans. However, efficient human-to-human transmission has not yet been observed. Here, we demonstrate that an H5N1 virus isolated from bovine milk in Texas in 2024 (H5N1Tex/24) replicates in differentiated human nasal epithelial cells as efficiently as a 2009 pandemic H1N1 virus strain (H1N1HH4/09) at both 37 {degrees}C and 33 {degrees}C. The adaptive mutations PB2-M631L and PA-K497R do not affect H5N1Tex/24 replication at 37 {degrees}C but promote replication at 33 {degrees}C. Conversely, H5N1BE/22, a virus from the same clade isolated from a pelican in 2022 that lacks these mutations, replicates in human nasal epithelial cells at 37 {degrees}C as efficiently as H5N1Tex/24 but exhibits limited replication at 33 {degrees}C. Introducing the two mutations PB2-M631L and PA-K497R did not overcome this limitation. Furthermore, nasal epithelial cells express receptors for both human and avian influenza viruses. Accordingly, no mutations were detected in HA which are known to switch receptor preference. Finally, we demonstrate that H5N1Tex/24 remains sensitive to the antiviral effects of interferon-{lambda} (IFN-{lambda}), however, infected nasal epithelial cells secrete only small amounts of this cytokine. Overall, our results suggest that H5N1Tex/24 possesses intrinsic traits enabling efficient replication in the human upper airways.

microbiology↗

bioRxiv2025

Deep learning-based 3D spatial transcriptomics with X-Pression

Spatial transcriptomics technologies currently lack scalable and cost-effective options to profile tissues in three dimensions. Technological advances in microcomputed tomography enabled non-destructive volumetric imaging of tissue blocks with sub-micron resolution at a centimetre scale. Here, we present X-Pression, a deep convolutional neural network-based frame-work designed to reconstruct 3D expression signatures of cellular niches from volumetric microcomputed tomography data. By training on a singular 2D section of a paired spatial transcriptomics experiment, X-Pression achieves high accuracy and is capable of generalising to out-of-sample examples. We utilised X-Pression to demonstrate the benefit of 3D examination of tissues on a paired SARS-CoV-2 vaccine efficacy spatial transcriptomics and microcomputed tomography cohort of a recently developed live attenuated SARS-CoV-2 vaccine. By applying X-Pression to the entire mouse lung, we visualised the sites of viral replication at the organ level and the simultaneous collapse of small alveoli in their vicinity. In addition, we assessed the immunological response following vaccination and virus challenge infection. X-Pression offers a valuable and cost-effective addition to infer expression signatures without the need for consecutive 2D sectioning and reconstruction, providing new insights into transcriptomic profiles in three dimensions.

bioinformatics↗

bioRxiv2023

A Taxonomically-informed Mass Spectrometry Search Tool for Microbial Metabolomics Data

MicrobeMASST, a taxonomically-informed mass spectrometry (MS) search tool, tackles limited microbial metabolite annotation in untargeted metabolomics experiments. Leveraging a curated database of >60,000 microbial monocultures, users can search known and unknown MS/MS spectra and link them to their respective microbial producers via MS/MS fragmentation patterns. Identification of microbial-derived metabolites and relative producers, without a priori knowledge, will vastly enhance the understanding of microorganisms role in ecology and human health.

microbiology↗

bioRxiv2022

The spike gene is a major determinant for the SARS-CoV-2 Omicron-BA.1 phenotype

Variant of concern (VOC) Omicron-BA1 has achieved global predominance in early 2022. Therefore, surveillance and comprehensive characterization of Omicron-BA.1 in advanced primary cell culture systems and multiple animal models is urgently needed. Here, we characterized Omicron-BA.1 and recombinant Omicron-BA.1 spike gene mutants in comparison with VOC Delta in well-differentiated primary human nasal and bronchial epithelial cells in vitro, followed by in vivo fitness characterization in naive hamsters, ferrets and hACE2-expressing mice, and in immunized hACE2-mice. We demonstrate a spike-mediated enhancement of early replication of Omicron-BA.1 in nasal epithelial cultures, but limited replication in bronchial epithelial cultures. In Syrian hamsters, Delta showed dominance over Omicron-BA.1 and in ferrets, Omicron-BA.1 infection was abortive. In mice expressing the authentic hACE2-receptor, Delta and a Delta spike clone also showed dominance over Omicron-BA.1 and an Omicron-BA.1 spike clone, respectively. Interestingly, in naive K18-hACE2 mice, we observed Delta spike-mediated increased replication and pathogenicity and Omicron-BA.1 spike-mediated reduced replication and pathogenicity, suggesting that the spike gene is a major determinant of both Delta and Omicron-BA.1 replication and pathogenicity. Finally, the Omicron-BA.1 spike clone was less well controlled by mRNA-vaccination in K18-hACE2-mice and became more competitive compared to the progenitor and Delta spike clones, suggesting that spike gene-mediated immune evasion is another important factor that led to Omicron-BA.1 dominance.

microbiology↗