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Akhil C. Banerjea

Bio: Akhil C. Banerjea is an academic researcher from International Centre for Diarrhoeal Disease Research, Bangladesh. The author has contributed to research in topics: RNA & Gene. The author has an hindex of 22, co-authored 90 publications receiving 1467 citations.
Topics: RNA, Gene, Virus, Transactivation, DNA


Papers
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Journal ArticleDOI
TL;DR: The results suggest the involvement of miRNA/RNAi pathways in dengue virus establishment and that d Dengue virus NS4B protein plays an important role in the modulation of the host RNAi/miRNA pathway to favor dengued virus replication.
Abstract: RNA interference (RNAi) is an important antiviral defense response in plants and invertebrates; however, evidences for its contribution to mammalian antiviral defense are few. In the present study, we demonstrate the anti-dengue virus role of RNAi in mammalian cells. Dengue virus infection of Huh 7 cells decreased the mRNA levels of host RNAi factors, namely, Dicer, Drosha, Ago1, and Ago2, and in corollary, silencing of these genes in virus-infected cells enhanced dengue virus replication. In addition, we observed downregulation of many known human microRNAs (miRNAs) in response to viral infection. Using reversion-of-silencing assays, we further showed that NS4B of all four dengue virus serotypes is a potent RNAi suppressor. We generated a series of deletion mutants and demonstrated that NS4B mediates RNAi suppression via its middle and C-terminal domains, namely, transmembrane domain 3 (TMD3) and TMD5. Importantly, the NS4B N-terminal region, including the signal sequence 2K, which has been implicated in interferon (IFN)-antagonistic properties, was not involved in mediating RNAi suppressor activity. Site-directed mutagenesis of conserved residues revealed that a Phe-to-Ala (F112A) mutation in the TMD3 region resulted in a significant reduction of the RNAi suppression activity. The green fluorescent protein (GFP)-small interfering RNA (siRNA) biogenesis of the GFP-silenced line was considerably reduced by wild-type NS4B, while the F112A mutant abrogated this reduction. These results were further confirmed by in vitro dicer assays. Together, our results suggest the involvement of miRNA/RNAi pathways in dengue virus establishment and that dengue virus NS4B protein plays an important role in the modulation of the host RNAi/miRNA pathway to favor dengue virus replication.

165 citations

Journal ArticleDOI
TL;DR: It is shown that the DNA‐enzyme when introduced into a mammalian cell, results in decreased CD4‐CCR5‐gp160 mediated fusion of cell membranes, which is an attractive target in the host cell for interfering specifically with the virus‐host interaction.

87 citations

Journal ArticleDOI
TL;DR: A novel observation is revealed that curcumin causes potent degradation of Tat which may be one of the major mechanisms behind its anti HIV activity.
Abstract: HIV-1 Tat is an intrinsically unfolded protein playing a pivotal role in viral replication by associating with TAR region of viral LTR. Unfolded proteins are degraded by 20S proteasome in an ubiquitin independent manner. Curcumin is known to activate 20S proteasome and promotes the degradation of intrinsically unfolded p53 tumor suppressor protein. Since HIV-1 Tat protein is largerly unfolded, we hypothesized that Tat may also be targeted through this pathway. Curcumin treated Tat transfected HEK-293T cells showed a dose and time dependent degradation of Tat protein. Contrary to this HIV-1 Gag which is a properly folded protein, remained unaffected with curcumin. Semi-quantitative RT-PCR analysis showed that curcumin treatment did not affect Tat gene transcription. Curcumin increased the rate of Tat protein degradation as shown by cycloheximide (CHX) chase assay. Degradation of the Tat protein is accomplished through proteasomal pathway as proteasomal inhibitor MG132 blocked Tat degradation. Curcumin also decreased Tat mediated LTR promoter transactivation and inhibited virus production from HIV-1 infected cells. Taken together our study reveals a novel observation that curcumin causes potent degradation of Tat which may be one of the major mechanisms behind its anti HIV activity.

85 citations

Journal ArticleDOI
29 Jun 2012-PLOS ONE
TL;DR: The distribution pattern of HIV-1 subtypes in India is characterised based on data collection from nationwide clinical cohorts between 2007 and 2011 and the time to the most recent common ancestor (tMRCA) of the predominant HIV- 1C strains is reconstructed.
Abstract: Background: India has the third largest HIV-1 epidemic with 2.4 million infected individuals. Molecular epidemiological analysis has identified the predominance of HIV-1 subtype C (HIV-1C). However, the previous reports have been limited by sample size, and uneven geographical distribution. The introduction of HIV-1C in India remains uncertain due to this lack of structured studies. To fill the gap, we characterised the distribution pattern of HIV-1 subtypes in India based on data collection from nationwide clinical cohorts between 2007 and 2011. We also reconstructed the time to the most recent common ancestor (tMRCA) of the predominant HIV-1C strains. Methodology/Principal Findings: Blood samples were collected from 168 HIV-1 seropositive subjects from 7 different states. HIV-1 subtypes were determined using two or three genes, gag, pol, and env using several methods. Bayesian coalescent-based approach was used to reconstruct the time of introduction and population growth patterns of the Indian HIV-1C. For the first time, a high prevalence (10%) of unique recombinant forms (BC and A1C) was observed when two or three genes were used instead of one gene (p<0.01; p = 0.02, respectively). The tMRCA of Indian HIV-1C was estimated using the three viral genes, ranged from 1967 (gag) to 1974 (env). Pol-gene analysis was considered to provide the most reliable estimate 1971, (95% CI: 1965-1976)]. The population growth pattern revealed an initial slow growth phase in the mid-1970s, an exponential phase through the 1980s, and a stationary phase since the early 1990s. Conclusions/Significance: The Indian HIV-1C epidemic originated around 40 years ago from a single or few genetically related African lineages, and since then largely evolved independently. The effective population size in the country has been broadly stable since the 1990s. The evolving viral epidemic, as indicated by the increase of recombinant strains, warrants a need for continued molecular surveillance to guide efficient disease intervention strategies.

69 citations

Journal ArticleDOI
16 Jun 2011-Blood
TL;DR: A novel function of Vpu is established in modulating the stability of p53 protein that correlates positively with apoptosis during late stages of HIV-1 infection.

51 citations


Cited by
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Journal ArticleDOI
TL;DR: In this paper, the chemokine receptors CXCR4 and CCR5, members of the G protein-coupled receptor superfamily, have been identified as the principal coreceptors for T cell line-tropic and macrophagetropic HIV-1 isolates, respectively.
Abstract: In addition to CD4, the human immunodeficiency virus (HIV) requires a coreceptor for entry into target cells. The chemokine receptors CXCR4 and CCR5, members of the G protein-coupled receptor superfamily, have been identified as the principal coreceptors for T cell line-tropic and macrophage-tropic HIV-1 isolates, respectively. The updated coreceptor repertoire includes numerous members, mostly chemokine receptors and related orphans. These discoveries provide a new framework for understanding critical features of the basic biology of HIV-1, including the selective tropism of individual viral variants for different CD4 C target cells and the membrane fusion mechanism governing virus entry. The coreceptors also provide molecular perspectives on central puzzles of HIV-1 disease, including the selective transmission of macrophage-tropic variants, the appearance of T cell line-tropic variants in many infected persons during progression to AIDS, and differing susceptibilities of individuals to infection and disease progression. Genetic findings have yielded major insights into the in vivo roles of individual coreceptors and their ligands; of particular importance is the discovery of an inactivating mutation in the CCR5 gene which, in homozygous form, confers strong resistance to HIV-1 infection. Beyond providing new perspectives on fundamental aspects of HIV-1 transmission and pathogenesis, the coreceptors suggest new avenues for developing novel therapeutic and preventative strategies to combat the AIDS epidemic.

2,245 citations

DOI
01 Jan 2020

1,967 citations

Journal Article
TL;DR: A widely accepted receptor nomenclature system is described, ratified by the International Union of Pharmacology, that is facilitating clear communication in this area and updating current concepts of the biology and pharmacology of the chemokine system.
Abstract: Chemokine receptors comprise a large family of seven transmembrane domain G protein-coupled receptors differentially expressed in diverse cell types. Biological activities have been most clearly defined in leukocytes, where chemokines coordinate development, differentiation, anatomic distribution, trafficking, and effector functions and thereby regulate innate and adaptive immune responses. Pharmacological analysis of chemokine receptors is at an early stage of development. Disease indications have been established in human immunodeficiency virus/acquired immune deficiency syndrome and in Plasmodium vivax malaria, due to exploitation of CCR5 and Duffy, respectively, by the pathogen for cell entry. Additional indications are emerging among inflammatory and immunologically mediated diseases, but selection of targets in this area still remains somewhat speculative. Small molecule antagonists with nanomolar affinity have been reported for 7 of the 18 known chemokine receptors but have not yet been studied in clinical trials. Virally encoded chemokine receptors, as well as chemokine agonists and antagonists, and chemokine scavengers have been identified in medically important poxviruses and herpesviruses, again underscoring the importance of the chemokine system in microbial pathogenesis and possibly identifying specific strategies for modulating chemokine action therapeutically. The purpose of this review is to update current concepts of the biology and pharmacology of the chemokine system, to summarize key information about each chemokine receptor, and to describe a widely accepted receptor nomenclature system, ratified by the International Union of Pharmacology, that is facilitating clear communication in this area.

1,851 citations

Journal ArticleDOI
TL;DR: Current nucleic-acid-based approaches for gene silencing are overviews, and the application of siRNAs in particular in functional genomics and as potential therapeutics is focused on.
Abstract: Molecules that can specifically silence gene expression are powerful research tools. Much effort has been put into the development of such molecules and has resulted in the creation of different classes of potential therapeutic agents. Small interfering RNA (siRNA) is one of the latest additions to the repertoire of sequence-specific gene-silencing agents. The robustness of this approach has motivated numerous biotechnology organizations and academic institutions to develop siRNA libraries for high-throughput genome-wide screening in mammalian cells. This article first overviews current nucleic-acid-based approaches for gene silencing, and then focuses on the application of siRNAs in particular in functional genomics and as potential therapeutics.

898 citations

Journal Article
TL;DR: The use of small interfering RNA (siRNA) is one of the latest additions to the repertoire of sequence-specific gene-silencing agents as mentioned in this paper, and the robustness of this approach has motivated numerous biotechnology organizations and academic institutions to develop siRNA libraries for high-throughput genomewide screening in mammalian cells.
Abstract: Molecules that can specifically silence gene expression are powerful research tools. Much effort has been put into the development of such molecules and has resulted in the creation of different classes of potential therapeutic agents. Small interfering RNA (siRNA) is one of the latest additions to the repertoire of sequence-specific gene-silencing agents. The robustness of this approach has motivated numerous biotechnology organizations and academic institutions to develop siRNA libraries for high-throughput genome-wide screening in mammalian cells. This article first overviews current nucleic-acid-based approaches for gene silencing, and then focuses on the application of siRNAs in particular in functional genomics and as potential therapeutics.

819 citations