Biology subjects

Pandey, A. D.

Publications and source records attributed to Pandey, A. D..

4 recordsLinked to original sources

bioRxiv2026

Dengue Virus Serotype 2 Infection Transcriptionally Reprograms Host Neutrophils to Establish an Immunosuppressive Microenvironment in Mice

Dengue virus (DV) infection triggers profound alterations in host immune responses, yet the transcriptomic reprogramming of innate immune cells during disease progression remains incompletely understood. Here, we demonstrated that Dengue virus serotype 2 (DV-2) infection transcriptionally reprograms host neutrophils, establishing an immunosuppressive microenvironment that facilitates pathogenesis. Through scRNA transcriptomic profiling of bone marrow and spleen cells from the DV-2-infected AG129 mouse model, we delineated a distinct neutrophil signature that shows dynamic shifts in immature and activated populations over the course of dengue infection. We also characterized a specific Ly6Glow subpopulation, notably Fibrinogen-like protein 2 (FGL2)-expressing subsets, that appeared with disease progression. Serum FGL2 levels were significantly elevated in both DV-2-infected mice and human dengue-positive patients. Furthermore, treatment of splenocytes with FGL2 or FGL2-enriched neutrophil secretomes suppressed T cell functional activity and promoted an immunosuppressive phenotype. Together, these findings reveal how DV-2-driven neutrophil reprogramming shapes an immunosuppressive network, highlighting the importance of studying FGL2-expressing neutrophil subsets to understand dengue immunopathogenesis.

immunology↗

bioRxiv2025

Emetine dihydrochloride inhibits Chikungunya virus nsP2 helicase and shows antiviral activity in the cell culture and mouse model of virus infection

Chikungunya virus (CHIKV), a mosquito-borne alphavirus, causes frequent epidemics of chikungunya fever across the world and has become a significant medical challenge, warranting the development of novel antivirals. A cell imaging-based high-content screening of the Spectrum collection of small molecules, containing all the US and international drug molecules, identified Emetine dihydrochloride (ED) as a potent antiviral against CHIKV. ED inhibited CHIKV replication in the C57BL/6 mouse model of chikungunya disease, resulting in significantly lower viremia. Importantly, clinical symptoms of joint swelling were altogether absent in the CHIKV-infected mice treated with ED. In the ERMS cells, ED inhibited the CHIKV uptake, and the virus replication early during the virus life cycle by inhibiting the viral RNA synthesis, resulting in the inhibition of the viral protein synthesis. ED was predicted to bind the helicase domain of the CHIKV non-structural protein nsP2 by in silico methods. The ED binding to the nsP2 protein and its helicase domain was validated in vitro by microscale thermophoresis and isothermal titration calorimetry. Importantly, ED inhibited the CHIKV nsP2 helicase activity in vitro in a dose-dependent manner. These data demonstrate the potential of ED to be repurposed as a novel CHIKV antiviral, warranting clinical development. AUTHOR SUMMARYChikungunya virus (CHIKV) spreads through the bites of the virus-infected Aedes mosquitoes. The virus causes frequent epidemics of chikungunya fever involving severe joint edema and muscle pain. The virus activity has been recorded in more than 100 countries in Asia, Africa, South and Central America, and Europe, and it has become endemic in several regions of the world. In 2024, around 480,000 CHIKV cases and over 200 deaths were reported worldwide. While a CHIKV vaccine was recently approved, no virus-specific antiviral therapy is available. Considering the global medical significance of the virus, the development of effective CHIKV antivirals is a priority. With a view to repurposing an existing drug, we screened a collection of all the approved US and international drug molecules and identified Emetine dihydrochloride (ED) as a potent inhibitor of CHIKV replication in the cell culture model. The CHIKV-infected mice treated with ED showed reduced virus replication and no joint swelling, which is a typical clinical symptom of CHIKV disease. Our studies show that ED binds the CHIKV nsP2, inhibiting its helicase action, which is required for replicating the viral genomic RNA and producing the viral proteins. In the past, emetine has been used in humans to treat amoebiasis. Our work thus shows the potential of the drug emetine to be repurposed for treating CHIKV patients.

microbiology↗

bioRxiv2025

Identification and In Silico Characterization of Novel lncRNAs Associated with Dengue Infection

BackgroundLong noncoding RNAs (lncRNAs) are essential regulators of various biological processes in viral infections. In our previous study, we described the association of known lncRNAs with dengue disease progression. However, little is known about novel lncRNAs in the context of dengue infection. In this study, we aimed to identify novel lncRNAs and characterize their interaction with mRNAs during different stages of dengue infection using RNA sequencing (RNA-seq) technology to better understand their role in dengue pathogenesis. MethodsWe analyzed RNA-seq data (GSE94892) obtained from peripheral blood mononuclear cells (PBMCs) of 39 dengue-infected patients. RNA-seq data analysis was performed using the Tuxedo protocol, and the coding potential of novel transcripts was examined using CPC and CPAT tools. LncRNAs and cis-regulated mRNAs were identified through location-expression analysis within a 20 kbp genomic region surrounding the identified lncRNAs. ResultsWe identified and characterized a total of 65 novel lncRNAs differentially expressed during dengue disease progression. These included 34 long intergenic lncRNAs, 2 antisense lncRNAs, and 25 alternatively spliced lncRNAs classified based on their localization. Bioinformatics analysis predicted potential cis-regulated target genes. Co-expression analysis revealed a strong correlation between lncRNAs and genes enriched in pathways related to megakaryocyte development and platelet production, suggesting a potential role in dengue pathogenesis. Furthermore, comparison with miRBase-21 indicated that some of the identified lncRNAs could act as miRNA precursors, highlighting a novel function of lncRNAs in gene regulation. ConclusionWe developed an analytical pipeline to identify novel lncRNAs from RNA-seq data. Our analyses led to the identification of novel lncRNAs and their associated genes involved in dengue disease progression. These findings provide insights into the functional role of lncRNAs in dengue pathogenesis.

bioinformatics↗

bioRxiv2022

Insights into the Human Gut Virome by Sampling a Population from the Indian Subcontinent

Gut virome plays an important role in human physiology but remains poorly understood. This study reports an investigation of the human gut DNA-virome of a previously unexplored ethnic population through metagenomics of faecal samples collected from individuals residing in Northern India. Analysis shows that, similar to the populations investigated earlier, majority of the identified virome belongs to bacteriophages and a smaller fraction (< 20%) consists of viruses that infect animals, archaea, protists, multiple domains or plants. However, crAss-like phages, in this population, are dominated by the genera VII, VIII and VI. Interestingly, it also reveals the presence of a virus family, Sphaerolipoviridae, which has not been detected in the human gut earlier. Viral families, Siphoviridae, Myoviridae, Podoviridae, Microviridae, Herelleviridae and Phycodnaviridae are detected in all of the analyzed individuals, which supports the existence of a core virome. Lysogeny-associated genes were found in less than 10% of the assembled genomes and a negative correlation was observed in the richness of bacterial and free-viral species, suggesting that the dominant lifestyle of gut phage is not lysogenic. This is in contrast to some of the earlier studies. Further, several hundred high-quality viral genomes were recovered. Detailed characterization of these genomes would be useful for understanding the biology of these viruses and their significance in human physiology. ImportanceViruses are important constituents of the human gut microbiome but it remains poorly understood. The Indian subcontinent is a unique biogeographic region and the Indian population is known to harbour a distinct bacterial microbiome. However, the gut virome in this population has not been investigated earlier. Therefore, in this study, we investigated fecal samples of 12 healthy individuals to analyze their gut virome, through metagenomics.

microbiology↗