Biology subjects

Nordgren, J.

Publications and source records attributed to Nordgren, J..

3 recordsLinked to original sources

bioRxiv2026

Human enterochromaffin cells and apical-out intestinal organoids as models for human sapovirus infection

Human sapovirus is increasingly recognized as a significant cause of acute viral gastroenteritis, but in vitro studies have been limited due to the previous lack of cell models. In this study, we optimized two novel in vitro models for sapovirus infection: the human enteroendocrine cell (EEC) line GOT1 and apical-out 3D human enteroids. Using 31 sapovirus-positive fecal samples, we compared these models with the EEC-derived HuTu80, and human enteroid monolayers, both previously used for sapovirus infection. Among the analyzed samples, genotypes GI.1 (36%), GII.1 (32%), and GII.3 (26%) were identified, with GI.1 exhibiting the highest fecal viral load. We demonstrated that GOT1 cells supported replication of more of the samples containing GI.1 sapovirus (9 of 11) compared to HuTu80 (8 of 11) and with a generally higher replication fold change. Moreover, GOT1 cells were able to support the replication of several GII.1 (3 of 10) and GII.3 (5 of 8) samples, unlike HuTu80 cells that only supported replication of one sample with GII.3 and none of the GII.1 sapoviruses. Given that organoids are considered a more physiologically relevant model than transformed cell lines, we established a sapovirus infection model using human apical-out 3D enteroids. Compared to previously used enteroid monolayers, the apical-out model supported replication of a higher number of samples with GI.1 and with higher replication fold change. In conclusion, these findings provide valuable insights for future in vitro studies of sapovirus infection and replication, which may contribute to a better understanding of sapovirus cell tropism and pathogenesis. ImportanceUnderstanding sapovirus biology requires efficient, reliable, and physiologically relevant in vitro models. By systematically comparing four infection models using clinical samples from three common sapovirus genotypes, this study contributes to important information about differences in cellular susceptibility between these in vitro models. We identified the GOT1 cell line as an efficient model for sapovirus replication and introduced apical-out enteroids as a sensitive organoid-based system for studying sapovirus GI.1. Together, the introduced models provide complementary platforms that can contribute to knowledge about sapovirus pathogenesis and cell tropism as well as provide guidance in selecting suitable in vitro models for future sapovirus research.

microbiology↗

bioRxiv2024

Altered DNA methylation pattern contributes to differential epigenetic immune signaling in the upper respiratory airway of COVID-19 patients

The emergence of SARS-CoV-2 has had a profound adverse impact on global health and continues to remain a threat worldwide. The disease spectrum of COVID-19 ranges from asymptomatic to fatal clinical outcomes especially in the elderly population and in individuals with underlying medical conditions. The impact of COVID-19 on host immune responses and immune cells at the protein and DNA levels remains largely ambiguous. In a case-control study, here we explored the impact of COVID-19 on DNA methylation patterns in the upper respiratory airway to determine how SARS-CoV-2 infection altered the immune status of individuals requiring hospitalization for COVID-19. We performed DNA methylation arrays on nasopharyngeal swabs at inclusion/hospitalization as well as 6 weeks post-inclusion. Our study reveals a distinct DNA methylation pattern in COVID-19 patients compared to healthy controls, characterized by 317 779 differentially methylated CpGs. Notably, within the transcription start sites and gene body, COVID-19 patients exhibited a higher number of genes/CpGs with elevated methylation levels. Enrichment analysis of methylated genes at transcription start sites highlighted the impact on genes associated with inflammatory responses and immune functions. Some SARS-CoV-2 -induced CpG methylations were transient, returning to normal levels by 6 weeks post-inclusion. Enriched genes of interest included IL-17A, a pivotal cytokine implicated with inflammation and healing, and NUP93, associated with antiviral innate immunity. Further, six genes in our data set, OAS1, CXCR5, APP, CCL20, CNR2, and C3AR1, were found in enrichment analysis with previous COVID-19 studies. Additionally, RNAse1 and RNAse2 emerged as key regulators, while IL-18 played a role in various biological processes in COVID-19 patients. Overall, our results demonstrates that COVID-19 has a major impact on the upper airway by modifying the methylation pattern of many genes and this could have implications for the conditioning of the airways and how the individual response to future airway infections.

microbiology↗

bioRxiv2022

Lasting alterations in monocyte and dendritic cell subsets in individuals after hospitalization for COVID-19

After more than two years the COVID-19 pandemic continues to burden healthcare systems and economies worldwide, and it is evident that long-term effects of the disease can persist for months post-recovery in some individuals. The activity of myeloid cells such as monocytes and dendritic cells (DC) is essential for correct mobilization of the innate and adaptive responses to a pathogen. Impaired levels and responses of monocytes and DC to SARS-CoV-2 is likely to be a driving force behind the immune dysregulation that characterizes severe COVID-19. Here, we followed, for 6-7 months, a cohort of COVID-19 patients hospitalized during the early waves of the pandemic. The levels and phenotypes of circulating monocyte and DC subsets were assessed to determine both the early and long-term effects of the SARS-CoV-2 infection. We found increased monocyte levels that persisted for 6-7 months, mostly attributed to elevated levels of classical monocytes. While most DC subsets recovered from an initial decrease, we found elevated levels of cDC2/cDC3 at the 6-7 month timepoint. Analysis of functional markers on monocytes and DC revealed sustained reduction in PD-L1 expression but increased CD86 expression across almost all cell types examined. Finally, viral load and CRP correlated to the appearance of circulating antibodies and levels of circulating DC and monocyte subsets, respectively. By elucidating some of the long-term effects that SARS-CoV-2 infection has on these key innate myeloid cells, we have shed more light on how the immune landscape remains affected in the months following severe COVID-19.

immunology↗