Biology subjects

Maharjan, A.

Publications and source records attributed to Maharjan, A..

3 recordsLinked to original sources

bioRxiv2026

Dengue serotype-1 virus like particles induce antibody responses following HeLa cell expression

Dengue disease remains a significant global health threat, with current vaccines exhibiting variable efficacy and safety concerns. Virus-like particles (VLPs) offer a promising alternative by mimicking native virus structures without infectious genomes. We engineered a mammalian expression plasmid encoding Dengue-1 prM and E proteins, optimized for secretion using Japanese Encephalitis virus signal sequences, and transiently expressed it in HeLa cells. Purified VLPs exhibited spherical morphology ([~]39 nm diameter) consistent with native virions, as confirmed by transmission electron microscopy. Immunization of mice with these VLPs elicited robust Dengue-1 specific IgG antibody responses. Our study demonstrates production of immunogenic Dengue-1 VLPs in HeLa cells, highlighting their potential as a vaccine candidate and a tool for serodiagnosis. Further characterization of VLP epitopes and protective efficacy is warranted to advance vaccine development. ImportanceDengue remains a significant global health challenge, with serotype 1 being one of the dominant strains causing recurrent outbreaks in Nepal. Existing vaccines demonstrate limited efficacy and pose significant safety concerns, particularly in seronegative populations. To address these limitations, this study explores virus-like particles (VLPs) as a safer alternative vaccine platform. VLPs elicit robust immunogenicity by mimicking the structure of native virus while completely lacking genetic components. This study combines DENV1 structural proteins with optimized expression systems to enhance immunogenicity. This work is particularly significant as the first dengue vaccine research conducted in Nepal, directly addressing antigenic mismatches between existing commercial vaccines and locally circulating viral strains. Furthermore, the study provides scalable platform for developing region-specific dengue vaccines for other serotypes and flaviviruses.

immunology↗

bioRxiv2025

The Cortical Output System that Controls a Single Vibrissa Muscle

What is the neural substrate that enables the cerebral cortex to control a single mystacial vibrissa and orchestrate its movement? To answer this question, we injected rabies virus into the intrinsic muscle that protracts the rat C3 vibrissa and used retrograde transneuronal transport to identify the cortical neurons that control the muscle. A surprisingly diverse set of cortical areas is the origin of disynaptic control over the motoneurons that influence the C3 protractor. More than two thirds of these layer 5 pyramidal neurons (L5PNs) are dispersed in frontal and parietal areas outside the primary motor cortex (vM1). This observation emphasizes the importance of descending commands from non-primary motor areas. More than a third of the L5PNs originate from somatosensory areas, such as the barrel field (vS1). The barrel field has been long considered a prototypic model system for studying sensory processing at the level of the cerebral cortex. Even so, we find that the number of L5PNs in vS1, and even their peak density, rivals the number and peak density of L5PNs in vM1. Thus, our results emphasize the importance of the barrel field in processing motor output. The distribution of L5PNs in vM1 and vS1 leads us to propose a new model of vibrissa protraction in which vM1 output results in protraction, and vS1 output results in reciprocal inhibition (suppression) of protraction. This paired initiation and suppression of complementary movements may be a general feature of the descending control signals from the rodent M1 and S1.

neuroscience↗

bioRxiv2025

IRF7 controls spontaneous autoimmune germinal center and plasma cell checkpoints

How IRF7 promotes autoimmune B cell responses and systemic autoimmunity is unclear. Analysis of spontaneous SLE-prone mice deficient in IRF7 uncovered the IRF7 role in regulating autoimmune germinal center (GC), plasma cell (PC) and autoantibody responses and disease. IRF7, however, was dispensable for foreign antigen driven GC, PC and antibody responses. Competitive bone marrow (BM) chimeras highlighted the importance of IRF7 in hematopoietic cells in spontaneous GC and PC differentiation. Single-cell-RNAseq of SLE-prone B cells indicated IRF7 mediated B cell differentiation through GC and PC fates. Mechanistic studies revealed that IRF7 promoted B cell differentiation through GC and PC fates by regulating the transcriptome, translation, and metabolism of SLE-prone B cells. Mixed BM chimeras demonstrated a requirement for B cell-intrinsic IRF7 in IgG autoantibody production but not sufficient for promoting spontaneous GC and PC responses. Altogether, we delineate previously unknown B cell-intrinsic and -extrinsic mechanisms of IRF7-promoted spontaneous GC and PC responses, loss of tolerance, autoantibody production and SLE development. SummaryFike et al. describe previously unknown mechanisms by which IRF7 controls autoimmune B cell and autoantibody responses. Mechanistic studies guided by single-cell-RNAseq and ChIPseq reveal that IRF7 promotes B cell differentiation through germinal center and plasma cell fates by regulating the transcriptome, translation, and metabolism of lupus-prone B cells.

immunology↗