Year: 2025
Type: article
Abstract: Description While many patients only experience flu like symptoms after contracting SARS-CoV-2, a small subset of patients will go on to develop acute respiratory distress syndrome (ARDS). ARDS is characterized by an overzealous inflammatory response brought on by downstream signaling of pattern recognition receptors. One such receptor, NLRX1, is shown to negatively regulate downstream inflammatory signaling during viral infections. However, its actions can be dichotomous depending on cellular context. ssRNA can be sensed by the C-terminal of NLRX1 implicating it in the host response of ssRNA viruses, such as SARS-CoV-2. The exact role of NLRX1 during SARS-CoV-2 infection remains unclear. We show NLRX1 to be protective in SARS-CoV-2 pathology. snRNA data taken from COVID-19 positive lung autopsy samples showed a down regulation of NLRX1 in airway epithelial cells while pathways modulated by NLRX1 were shown to be deferentially enriched. Nlrx1-/- mice infected with the mouse adapted SARS-CoV-2 virus had a greater viral titer and airway inflammation, including increased cellular denuding at 2 days post infection compared to wild-type animals. Furthermore, human airway epithelial cells over-expressing NLRX1, not only had decreased viral replication but may be protecting against a viral shift of host metabolism to limit viral replication. Our results suggest NLRX1 antagonizes SARS-CoV-2 through multiple pathways. With more research, NLRX1 could be a promising drug target for Covid-19. Topic Categories Viral Immunology (VIR)
Source: The Journal of Immunology
Institution: Virginia Tech
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4416446415
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