Immunoinformatic approach to design T cell epitope-based chimeric vaccine targeting multiple serotypes of dengue virus DOI
Nilanshu Manocha, Prakash Jha, Prashant Kumar

et al.

Journal of Biomolecular Structure and Dynamics, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 19

Published: Nov. 28, 2024

The global dengue outbreak is a significant public health concern, with the World Health Organization recording over 3 million cases and 0.04% case fatality rate until July 2023. infection anticipated to rise in vulnerable regions worldwide. While live-attenuated vaccines are current standard, their effectiveness certain populations debated. Furthermore, presence of four closely related virus serotypes can lead antibody-dependent enhancement, compromising vaccine efficacy. In response, we propose development therapeutic subunit-vaccine based on epitopes from all induce robust cross-protective cellular immunity. Our approach involves designing multi-epitope chimeric immunogen using envelope protein virus. MHC-I MHC-II binding T-cell were selected antigen processing criteria. most potent immunodominant for each serotype, considering immunogenicity, population coverage, prediction scores, combined AAY linker peptides create stable polypeptide. Predicted be both antigenic non-allergenic, design exhibits soluble tertiary structure half-life 4.4 h mammalian systems. addition, employed an agonist toll-like receptor-4 at N-terminal downstream immunostimulatory validated through docking molecular dynamics simulations. This construct shows promise eliciting effective immune response against serotypes.

Language: Английский

Pinocembrin reduces pyroptosis to improve flap survival by modulating the TLR4/NF-κB/NLRP3 signaling pathway DOI

Kaitao Wang,

Jialong Yang, Jiapeng Deng

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2025, Volume and Issue: 1871(3), P. 167710 - 167710

Published: Feb. 8, 2025

Language: Английский

Citations

1
Role of interferons in the antiviral battle: from virus-host crosstalk to prophylactic and therapeutic potential in SARS-CoV-2 infection DOI Creative Commons

Grigore Mihăescu,

Mariana Carmen Chifiriuc, Roxana Filip

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 15, 2024

Mammalians sense antigenic messages from infectious agents that penetrate the respiratory and digestive epithelium, as well signals damaged host cells through membrane cytosolic receptors. The transduction of these triggers a personalized response, depending on nature stimulus host’s genetics, physiological condition, comorbidities. Interferons (IFNs) are primary effectors innate immune their synthesis is activated in most within few hours after pathogen invasion. IFNs primarily synthesized infected cells, but anti-infective effect extended to neighboring by autocrine paracrine action. emergence severe acute syndrome coronavirus 2 (SARS‐CoV‐2) pandemic 2019 was stark reminder potential threat posed newly emerging viruses. This has also triggered an overwhelming influx research studies aiming unveil mechanisms protective versus pathogenic responses induced SARS‐CoV‐2. purpose this review describe role vital players battle against SARS‐CoV-2 infection. We will briefly characterize classify IFNs, present inductors IFN synthesis, sensors, signaling pathways, then discuss controlling evolution SARS-CoV-2 infection its clinical outcome. Finally, we perspectives controversies regarding prophylactic therapeutic

Language: Английский

Citations

7
TLR2/4 are novel activating receptors for SARS-CoV-2 spike protein on NK cells DOI Creative Commons
Nadine Landolina, Biancamaria Ricci, Irene Veneziani

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: May 31, 2024

In early infected or severe coronavirus disease 2019 (COVID-19) patients, circulating NK cells are consistently reduced, despite being highly activated exhausted. The aim of this paper was to establish whether acute respiratory syndrome 2 (SARS-CoV-2) spike glycoprotein (SP) may directly trigger and through which receptor(s).

Language: Английский

Citations

6
Virion-incorporated CD14 enables HIV-1 to bind LPS and initiate TLR4 signaling in immune cells DOI Creative Commons
Arvin Tejnarine Persaud,

Jasmin Khela,

Claire Fernandes

et al.

Journal of Virology, Journal Year: 2024, Volume and Issue: 98(5)

Published: April 25, 2024

ABSTRACT HIV-1 has a broad range of nuanced interactions with the immune system, and incorporation cellular proteins by nascent virions continues to redefine our understanding virus-host relationship. Proteins located at sites viral egress can be selectively incorporated into envelope, imparting new functions phenotypes onto virions, impacting spread disease. Using virion capture assays western blot, we show that incorporate myeloid antigen CD14 its envelope. Virion-incorporated remained biologically active able bind natural ligand, bacterial lipopolysaccharide (LPS), as demonstrated flow virometry immunoprecipitation assays. Toll-like receptor 4 (TLR4) reporter cell line, also bound LPS trigger TLR4 signaling activate transcription factors regulate inflammatory gene expression. Complementary THP-1 monocytes enhanced secretion cytokines like tumor necrosis factor alpha (TNF-α) C-C chemokine ligand 5 (CCL5), when exposed LPS-loaded virus. These data highlight type interplay between compartment, previously well-established contributor pathogenesis inflammation. Persistent gut inflammation is hallmark chronic infection, contributing this effect translocation microbes across epithelium. Our herein provide proof principle virion-incorporated could novel mechanism through which drive inflammation, facilitated particles binding initiating in TLR4-expressing cells. IMPORTANCE establishes lifelong infection accompanied numerous immunological changes. Inflammation epithelia, exacerbated loss mucosal T cells cytokine dysregulation, persists during infection. Feeding back loop intestinal resulting systemic dissemination antigens, (LPS). group receptor, CD14, readily particles, supporting previous clinical observations viruses derived from patient plasma. We now several primary isolates remain functional, enabling LPS. This subsequently allowed + transfer monocytic cells, eliciting pro-inflammatory secretion. posit here potential dysregulated responses present setting

Language: Английский

Citations

5
RNA viruses, TLRs, and cytokines: the perfect storm? DOI Creative Commons
Sophia K. Stegeman,

Olena Kourko,

Heather Amsden

et al.

Journal of Innate Immunity, Journal Year: 2025, Volume and Issue: 17(1), P. 126 - 153

Published: Jan. 16, 2025

The interactions between viruses and the host immune response are nuanced intricate. cytokine arguably plays a central role in dictating outcome of virus infection, balancing inflammation, healing, which is crucial to resolving infection without destructive immunopathologies. Early innate responses key generation beneficial or detrimental response. These initial regulated by plethora surface bound, endosomal, cytoplasmic receptors known as pattern recognition receptors. Of these, Toll-like (TLRs) play an important induction cytokines during infection. Recognizing pathogen-associated molecular patterns (PAMPs) such viral proteins and/or nucleotide sequences, TLRs act sentinels for initiation propagation responses. initiating single-stranded RNA (ssRNA) like influenza A (IAV), severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1), SARS-CoV-2, Middle East coronavirus, dengue virus, Ebola virus. Infection with these also associated aberrant expression proinflammatory that contribute harmful storm Herein we discuss connections ssRNA viruses, storm, roles TLRs.

Language: Английский

Citations

0
Tetrastigma hemsleyanum polysaccharide protects against “two-hit” induced severe pneumonia via TLR4/NF-κB signaling pathway DOI
Fangmei Zhou, Ying Guo, Wenxuan Li

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 140639 - 140639

Published: Feb. 1, 2025

Language: Английский

Citations

0
Innate immune evasion and general host shutoff strategies of human respiratory RNA viruses DOI

Juliette Bougon,

Denys A. Khaperskyy

Future Virology, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 17

Published: Feb. 17, 2025

Language: Английский

Citations

0
A self-adjuvant multiantigenic nanovaccines simultaneously activate the antiviral and antitumor immunity for the treatment of cancers DOI Creative Commons
Zhongjie Wang, Hanlin Chen,

Ruiqi Ming

et al.

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 27, 2025

Tumor cell-derived extracellular vesicles (tEVs) have garnered significant attention as promising antigen delivery vehicles for the development of cancer vaccines. However, their practical applications are hindered by weak immunogenicity and inadequate lymph node targeting. In this study, we engineered tEVs into "self-adjuvant" multiantigenic nanovaccines that simultaneously accumulate in tumors nodes (LNs), effectively triggering innate adaptive immunity capable recognizing both tumor cells virus antigen-modified to inhibit progression. 4T1 were infected with vesicular stomatitis (VSV), leading expression VSVG calreticulin (CRT) on surface. Using these cells, prepared (vEVs) carrying CRT. When injected subcutaneously, vEVs targeted due homologous targeting capability cell membranes. which, induced fusion between creating viral antigen-decorated which enhanced recognition phagocytosis macrophages. Additionally, surface CRT activated "eat-me" signaling, thus improving uptake dendritic (DCs). This led DC maturation activation antiviral antitumor T synergistically inhibiting growth. research introduces a straightforward yet efficacious methodology production vaccines fight through stimulation immune responses within body.

Language: Английский

Citations

0
Differences in Phage Recognition and Immunogenicity Contribute to Divergent Human Immune Responses to Escherichia coli and Klebsiella pneumoniae Phages DOI Creative Commons

Huu Thanh Le,

Carola Venturini, Alicia Fajardo Lubián

et al.

European Journal of Immunology, Journal Year: 2025, Volume and Issue: 55(3)

Published: March 1, 2025

ABSTRACT Bacteriophages (phages) are emerging as a viable adjunct to antibiotics for the treatment of multidrug‐resistant (MDR) bacterial infections. While intravenous phage therapy has proven successful in many cases, clinical outcomes remain uncertain due limited understanding host response phages. In this study, we conducted comprehensive examination interaction between clinical‐grade phages used treat MDR Escherichia coli and Klebsiella pneumoniae infections, human peripheral blood immune cells. Using whole transcriptome well proteomic approaches, identified strong inflammatory E. vB_EcoM‐JIPh_Ec70 (herein, JIPh_Ec70) that was absent upon exposure K. JIPh_Kp127. We confirmed JIPh_Ec70's DNA recognition by STING pathway principally responsible activation NF‐kB subsequent response. further show monocytes neutrophils play dominant role uptake, primarily through complement‐mediated phagocytosis. Significant differences phagocytosis JIPh_Kp127 JIPh_Ec70 were observed, suggesting reduced recognition, phagocytosis, immunogenicity all contribute significantly decreased Our findings progress our innate therapeutic offer potential insights into how improve safety effectiveness therapy.

Language: Английский

Citations

0
The MAPK Response to Virus Infection Is Modified by Probenecid DOI Creative Commons

Les Jones,

David E. Martin, Ralph A. Tripp

et al.

Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(4), P. 246 - 246

Published: April 2, 2025

Respiratory viruses such as respiratory syncytial virus (RSV) annually cause illness, which may result in substantial disease and mortality susceptible individuals. Viruses exploit host cell machinery for replication, engages the mitogen-activated protein kinases (MAPK) pathway. The MAPK signaling pathways are triggered by pattern recognition receptors that recognize pathogen, infection, or external stimuli, leading to induction regulation of immunity inflammation. Probenecid, used improve renal function inhibiting tubular reabsorption uric acid, has been shown have therapeutic efficacy reducing inflammation blocking viral replication components pathway preclude replication. This review summarizes key molecular cascades response recognition, how this can be altered probenecid treatment.

Language: Английский

Citations

0