A5101757826- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- Immune Cell Function and Interaction
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- Virus-based gene therapy research
- Biochemical and Molecular Research
- Protein Degradation and Inhibitors
- RNA Research and Splicing
- Cancer-related molecular mechanisms research
- Monoclonal and Polyclonal Antibodies Research
- HIV/AIDS Research and Interventions
- Virology and Viral Diseases
- Herpesvirus Infections and Treatments
- Animal Disease Management and Epidemiology
- interferon and immune responses
- Viral gastroenteritis research and epidemiology
- Viral Infections and Immunology Research
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- Mosquito-borne diseases and control
- Viral Infections and Vectors
- Antimicrobial Peptides and Activities
- Cytomegalovirus and herpesvirus research
- Advanced Breast Cancer Therapies
The Ohio State University
2013-2025
University Hospital Bonn
2024-2025
Birla Institute of Technology, Mesra
2023
Dr. Yashwant Singh Parmar University of Horticulture and Forestry
2022
National Institute of Malaria Research
2022
Academy of Scientific and Innovative Research
2022
Fred Hutch Cancer Center
2015-2020
Seattle University
2015
Rutgers, The State University of New Jersey
2014
Sylvester Comprehensive Cancer Center
2013
The selection of chromosomal targets for retroviral integration varies markedly, tracking with the genus retrovirus, suggestive targeting by binding to cellular factors. γ-Retroviral murine leukemia virus (MLV) DNA into host genome is favored at transcription start sites, but underlying mechanism this preference unknown. Here, we have identified bromodomain and extraterminal domain (BET) proteins (Brd2, -3, -4) as cellular-binding partners MLV integrase. We show that purified recombinant...
Retroviral replication proceeds through an obligate integrated DNA provirus, making retroviral vectors attractive vehicles for human gene-therapy. Though most of the host cell genome is available integration, process integration site selection not random. Retroviruses differ in their choice chromatin-associated features and also prefer particular nucleotide sequences at point insertion. Lentiviruses including HIV-1 preferentially integrate within bodies active genes, whereas prototypical...
The quinoline-based allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) are promising candidates for clinically useful antiviral agents. Studies using these compounds have highlighted the role of IN in both early and late stages virus replication. However, dissecting exact mechanism action ALLINIs has been complicated by multifunctional nature because they inhibit binding with its cofactor LEDGF/p75 promote aberrant multimerization similar potencies vitro. Here we report design small...
Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 is a novel and highly pathogenic the causative agent of disease 2019 (COVID-19). The high morbidity mortality associated with COVID-19 lack an approved drug or vaccine for SARS-CoV-2 underscores urgent need developing effective antiviral therapies. Therapeutics that target essential viral proteins are at controlling virus replication spread. Coronavirus Spike glycoproteins mediate entry fusion host cell, thus replication. To enter...
Retroviruses rely on host RNA-binding proteins to modulate various steps in their replication. Previously several animal retroviruses were determined mediate Dhx9/RNA helicase A (RHA) interaction with a 5' terminal post-transcriptional control element (PCE) for efficient translation. Herein PCE reporter assays HTLV-1 and HIV-1 RU5 confer orientation-dependent activity. The effect of Dhx9/RHA down-regulation rescue siRNA-resistant RHA expression HIV-1(NL4-3) provirus that is necessary RNA...
Translation is a regulated process and pivotal to proper cell growth homeostasis. All retroviruses rely on the host translational machinery for viral protein synthesis thus may be susceptible its perturbation in response stress, co-infection, and/or cycle arrest. HIV-1 infection arrests G2/M phase, potentially disrupting regulation of translation. In this study, we present evidence that downregulates translation lymphocytes, attributable arrest induced by accessory Vpr. The molecular basis...
We report alterations to the murine leukemia virus (MLV) integrase (IN) protein that successfully result in decreasing its integration frequency at transcription start sites and CpG islands, thereby reducing potential for insertional activation. The host bromo extraterminal (BET) proteins Brd2, 3 4 interact with MLV IN primarily through BET ET domain. Using solution NMR, interaction studies, next generation sequencing, we show C-terminal tail peptide region of is important disruption this...
Butyrate is an abundant metabolite produced by gut microbiota. While butyrate a known histone deacetylase inhibitor that activates expression of many genes involved in immune system pathways, its effects on virus infections and the antiviral type I interferon (IFN) response have not been adequately investigated. We found increases cellular infection with viruses relevant to human animal health, including influenza virus, reovirus, HIV-1, metapneumovirus, vesicular stomatitis virus....
5-methylcytosine (m 5 C) is one of the most prevalent modifications RNA, playing important roles in RNA metabolism, nuclear export, and translation. However, potential role m C methylation innate immunity remains elusive. Here, we show that depletion NSUN2, an methyltransferase, significantly inhibits replication gene expression a wide range DNA viruses. Notably, found this antiviral effect largely driven by enhanced type I interferon (IFN) response. The signaling pathway dependent on...
N6-Methyladenosine (m6A) is the most abundant internal RNA modification catalyzed by host methyltransferases. As obligate intracellular parasites, many viruses acquire m6A methylation in their RNAs. However, biological functions of viral are poorly understood. Here, we found that serves as a molecular marker for innate immunity to discriminate self from nonself and this novel function universally conserved several families nonsegmented negative-sense (NNS) viruses. Using methyltransferase...
The decoction of the whole plant Enhydra fluctuans is used ethno medicinally by various tribes for treatment kidney stones and urinary problems. However, no scientific studies were carried out to delineate its influence on stone formation crystallisation. Hence, present study proposed investigate effect aqueous extract in vitro crystallisation calcium oxalate. also evaluated. silico metabolites with target proteins renal oxalate matrix. material was subjected obtain an extract....
Abstract Despite the favorable effects of immunotherapies in multiple types cancers, its complete success CNS malignancies remains challenging. Recently, a successful clinical trial cytokine-induced killer (CIK) cell immunotherapy patients with glioblastoma (GBM) has opened new avenue for adoptive cellular malignancies. Prompt from these findings, herein, we investigated whether dendritic cells (DC) combination (DC-CIK) could also provide an alternative and more effective way to improve...
HIV-1 envelope glycoproteins (Envs) mediate viral entry and are sole target of neutralizing antibodies. Thus, Envs must maintain a delicate balance between evading antibodies while still preserving compatibility to into cells. Here, we studied the effeciency, fitness, replication an incompletely closed, transmitted/founder (CH040), which highly resistant most bnAbs. CH040 mediated cells as efficient other primary Envs, suggesting that antibody resistance can develop independently. Expression...
The importance of understanding the molecular mechanisms murine leukemia virus (MLV) integration into host chromatin is highlighted by development MLV-based vectors for human gene-therapy. We have recently identified BET proteins (Brd2, 3 and 4) as main cellular binding partners MLV integrase (IN) demonstrated their significance effective at transcription start sites. Here we show that recombinant Brd4, a representative three proteins, establishes complementary high-affinity interactions...
Allosteric HIV-1 integrase inhibitors (ALLINIs) have recently emerged as a promising class of antiretroviral agents and are currently in clinical trials. In infected cells, ALLINIs potently inhibit viral replication by impairing virus particle maturation but surprisingly exhibit reduced EC50 for inhibiting integration target cells. To better understand the antiviral activity during early stage replication, we investigated competitive interplay between potent representative ALLINI, BI/D,...
Human respiratory syncytial virus (RSV) is the leading cause of tract infections in humans. A well-known challenge development a live attenuated RSV vaccine that interferon (IFN)-mediated antiviral responses are strongly suppressed by nonstructural proteins which, turn, dampens subsequent adaptive immune responses. Here, we discovered novel strategy to enhance innate and immunity infection. Specifically, found recombinant RSVs deficient viral RNA N 6 -methyladenosine (m A) grown m...
Most HIV-1 variants isolated from early-stage human infections do not use nonhuman primate versions of the CD4 receptor for cellular entry, or they so poorly. We and others have previously shown that has experienced strong natural selection over course speciation, but it is unclear whether this influenced functional characteristics as an receptor. Surprisingly, we find on been most intense in New World monkeys, animals never found to harbor lentiviruses related HIV-1. Based this, sampled...
In view of the ethno medicinal use Enhydra fluctuans for treatment kidney stones; present study aimed to elucidate molecular mechanisms involved in amelioration nephrolithiasis through a network pharmacology approach. The phytoconstituents were queried DIGEP-Pred identify regulated proteins. modulated proteins then enriched STRING predict protein-protein interactions and probably pathways traced Kyoto Encyclopedia Genes Genomes. Further, was constructed using Cytoscape ver 3.5.1. Results...
SHIV/macaque model is critical for pre-clinical HIV-1 research. The ability of this to predict efficacious intervention(s) in humans depends on how faithfully the recapitulates key features transmission and pathogenesis. Here, we provide insights rationally designing SHIVs with transmitted variants vaccine prevention
Type-I interferon (IFN-I) is a major antiviral host response but its impact on Zika virus (ZIKV) replication not well defined, particularly as it relates to different circulating strains. Interferon stimulated genes (ISGs) that inhibit ZIKV, such IFITM3, have been identified largely using overexpression studies. Here, we tested whether diverse ZIKV strains differed in their susceptibility IFN-I-mediated restriction and the contribution of IFITM3 this restriction. We robust effect...