Biology subjects

Shrivastava, S.

Publications and source records attributed to Shrivastava, S..

4 recordsLinked to original sources

bioRxiv2022

SARS-CoV-2 Variant Delta Potently Suppresses Innate Immune Response and Evades Interferon-Activated Antiviral Responses

Delta variant of SARS-CoV-2 has caused more severe infections than its previous variants. We studied the host innate immune response to Delta, Alpha and two earlier variants to map the evolution of the recent ones. Our biochemical and transcriptomic studies reveal that Alpha and Delta have progressively evolved over the ancestral variants by silencing innate immune response, thereby limiting cytokine and chemokine production. Though Alpha silenced RLR pathway just as Delta, it failed to persistently silence the innate immune response unlike Delta. Both Alpha and Delta have evolved to resist IFN treatment while they are still susceptible to RLR activation, further highlighting the importance of RLR-mediated, IFN-independent mechanisms in restricting SARS-CoV-2. Our studies reveal that SARS-CoV-2 Delta has integrated multiple mechanisms to silence host innate immune response and evade IFN response. Deltas silent replication and sustained suppression of host innate immune response, possibly resulting in delayed or reduced intervention by the adaptive immune response, could potentially contribute to the severe symptoms and poor recovery index associated with it.

immunology↗

bioRxiv2021

A spike-ferritin nanoparticle vaccine induces robust innate immune activity and drives polyfunctional SARS-CoV-2-specific T cells

Potent cellular responses to viral infections are pivotal for long -lived protection. Evidence is growing that these responses are critical in SARS -CoV-2 immunity. Assessment of a SARS -CoV-2 spike ferritin nanoparticle (SpFN) immunogen paired with two distinct adjuvants, Alhydrogel(R) (AH) or Army Liposome Formulation containing QS-21 (ALFQ) demonstrated unique vaccine evoked immune signatures. SpFN+ALFQ enhanced recruitment of highly activated classical and non -classical antigen presenting cells (APCs) to the vaccine-draining lymph nodes of mice. The multifaceted APC response of SpFN+ALFQ vaccinated mice was associated with an increased frequency of polyfunctional spike -specific T cells with a bias towards TH1 responses and more robust SARS-CoV-2 spike-specific recall response. In addition, SpFN+ALFQ induced Kb spike(539-546)-specific memory CD8+ T cells with effective cytolytic function and distribution to the lungs. This epitope is also present in SARS-CoV, thus suggesting that generation of cross-reactive T cells may provide protection against other coronavirus strains. Our study reveals that a nanoparticle vaccine, combined with a potent adjuvant, generates effective SARS-CoV-2 specific innate and adaptive immune T cell responses that are key components to inducing long-lived immunity. One Sentence SummarySpFN vaccine generates multifactorial cellular immune responses.

immunology↗

bioRxiv2020

Shock and Detonation Waves at an Interface and the Collision of Action Potentials

Action potentials in neurons are known to annihilate each other upon collision, while there are cases where they might penetrate each other. Compression waves that travel within the plasma membrane of a neuron have previously been proposed as a thermodynamic basis for the propagation of action potentials. In this context, it was recently shown that two-dimensional compressive shock waves in the model system of lipid monolayers can nearly annihilate each other upon head-on collision when excited close to a phase transition. However, weaker shock waves showed penetration. In general, once the approximation of small perturbation is not valid, compression waves do not interact linearly anymore. While experiments in lipid monolayers demonstrated this principle, a mechanism remained unclear. In this article, we summarise the fundamentals of shock physics as applied to an interface and how it previously explained the observation of threshold and saturation of shockwaves in the lipid monolayer (all - or - none). While the theory has the same fundamental premise as the soliton model, i.e. the conservation laws and thermodynamics, we elaborate on how the two approaches make different predictions with regards to collisions and the detailed structure of the wave-front. As a case study and a new result, we show that previously unexplained annihilation of shock waves in the lipid monolayer is a direct consequence of the nature of state changes, i.e. jump conditions, within these shockwaves, and elaborate on the consequence of these results for the general understanding of the excitation waves in a thermo-fluids framework.

biophysics↗

bioRxiv2020

A Thermodynamic Interpretation of the Stimulated Raman Spectroscopic Signature to Action Potential in Single Neurons

It has previously been suggested that the plasma membrane condenses and melts reversibly during an action potential in a neuron, analogous to an acoustic wave travelling in the compressive membrane region. If true it has fundamental consequences for our understanding of the regulation of biological functions during an action potential. It has long been known that the electrical dipoles in the neuronal membrane reorient during an action potential, observed through a variety of optical methods. However, this information has been insufficient to confirm if and how the collective thermodynamic state of the neuronal membrane changes during an action potential. Here, we show that hyperspectral stimulated Raman spectroscopy (SRS) can resolve the thermodynamic state of the neuronal membranes in a single neuron during an action potential. These measurements indicate that the system becomes ordered and compressed during the de-polarisation phase and disordered and expanded during hyper polarisation Therefore, the observation is consistent with the acoustic hypothesis and SRS provides a powerful tool to not only further validate the hypothesis in future, but also explore the role of membrane thermodynamics during an action potential.

biophysics↗