Stankevicius, A. | Search bioRxiv

bioRxiv2026

Omicron-Enhanced Immunosuppressive Effects of SARS-CoV-2 ORF3a and ORF9b Accessory Proteins on Monocytic Inflammatory Response

This study investigates the poorly understood roles of SARS-CoV-2 accessory proteins using monocytic THP-1 cells expressing individual viral ORFs. ORF3a, ORF7b, and ORF9b were identified as major immunomodulators that suppress host inflammatory signaling. Specifically, cells expressing ORF3a or ORF9b exhibited reduced Toll-like receptor 4 (TLR4)-mediated production of key proinflammatory molecules--CCL2, CCL4, and IL-1{beta}--resulting in diminished immune cell recruitment. Importantly, Omicron-associated mutations in ORF3a (T223I) and ORF9b (P10S+{Delta}E27N28A29) amplified this immunosuppressive effect, leading to stronger transcriptomic suppression consistent with Omicrons reduced pathogenicity and clinical outcomes. These findings suggest that SARS-CoV-2 accessory proteins, particularly ORF3a and ORF9b, play pivotal roles in modulating monocytic immune responses. Enhanced suppression in Omicron variants highlights an evolutionary adaptation contributing to immune evasion and milder disease manifestations.

immunology↗

bioRxiv2018

Neuroticism Impairs the Use of Reward Values for Decision-Making in Major Depression

Depression is a debilitating condition with a high prevalence, but aetiology and pathophysiology are still unclear. Various reward-learning paradigms have been used to show impairments in depression. Both trait pessimism and neuroticism are associated with depression, but their link with the impairments in reward learning and decision-making have not been investigated. A Pavlovian conditioning task was performed by 32 subjects, 15 with depression. Participants had to estimate the probability of some fractal stimuli to be associated with a binary reward, based on a few observations. They then had to make a choice between one of the observed fractals and another target for which the reward probability was explicitly given. Computational modelling was used to succinctly describe participants behaviour. Patients performed worse than controls at the task. Computational modelling revealed that this was caused by behavioural impairments during both learning and decision phases. Neuroticism scores across participants were significantly correlated with participants inability to follow their internal value estimations. Our results demonstrate behavioural differences in probabilistic reward learning between depressed patients and healthy controls. Neuroticism was associated with the impaired ability to follow internal reward values and consequently with worse decision-making.

neuroscience↗