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Pallob Kundu

Bio: Pallob Kundu is an academic researcher from Bose Institute. The author has contributed to research in topics: Promoter & Gene. The author has an hindex of 16, co-authored 27 publications receiving 720 citations. Previous affiliations of Pallob Kundu include University of California, Los Angeles & University of California.

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Journal ArticleDOI
TL;DR: For a small RNA virus that strictly replicates in the cytoplasm, a portion of its life cycle does include interaction with the host cell nucleus and recent studies indicate that the viral protease-polymerase precursor 3CD can enter nucleus in poliovirus-infected cells.

99 citations

Journal ArticleDOI
TL;DR: The results suggest 1007YNMLCFGIY1015 possible participation in Slo1 plasmalemmal targeting and demonstrate its role as a main mechanism for caveolin-1 association withSlo1 potentially serving a dual role: (i) maintaining channels in intracellular compartments downsizing their surface expression and/or (ii) serving as anchor of plasma membrane resident channels to caveolin -1-rich membranes.

73 citations

Journal ArticleDOI
TL;DR: VG16KRKP, a non-toxic and non-hemolytic analogue of VG16, shows significant antimicrobial activity against Gram-negative E. coli and plant pathogens X. oryzae and X. campestris, as well as against human fungal pathogens C. albicans and C. grubii.
Abstract: The recent increase in multidrug resistance against bacterial infections has become a major concern to human health and global food security Synthetic antimicrobial peptides (AMPs) have recently received substantial attention as potential alternatives to conventional antibiotics because of their potent broad-spectrum antimicrobial activity These peptides have also been implicated in plant disease control for replacing conventional treatment methods that are polluting and hazardous to the environment and to human health Here, we report de novo design and antimicrobial studies of VG16, a 16-residue active fragment of Dengue virus fusion peptide Our results reveal that VG16KRKP, a non-toxic and non-hemolytic analogue of VG16, shows significant antimicrobial activity against Gram-negative E coli and plant pathogens X oryzae and X campestris, as well as against human fungal pathogens C albicans and C grubii VG16KRKP is also capable of inhibiting bacterial disease progression in plants The solution-NMR structure of VG16KRKP in lipopolysaccharide features a folded conformation with a centrally located turn-type structure stabilized by aromatic-aromatic packing interactions with extended N- and C-termini The de novo design of VG16KRKP provides valuable insights into the development of more potent antibacterial and antiendotoxic peptides for the treatment of human and plant infections

72 citations

Journal ArticleDOI
TL;DR: A novel trypsin inhibitor from Indian mustard Brassica juncea that is unique in being the precursor of a 2S seed storage protein that can be used in transforming seed crops for protection to their vegetative parts and early seed stages, when insect damage is maximal.

53 citations

Journal ArticleDOI
TL;DR: Evidence is presented that suggests that the transcriptional inactivation of TBP by 3Cpro involves cleavage at the glutamine 104-serine 105 (Q104-S105) site of T BP and not at the Q18-G19 site as previously thought.
Abstract: Poliovirus (PV) is the prototype virus of a large group of medically important viruses (picornaviruses) that include those inducing poliomyelitis (polioviruses), infectious hepatitis (hepatitis A virus), the common cold (rhinoviruses), and encephalitis and myocarditis (coxsackie viruses) (31). The single-stranded, plus-polarity RNA genome (∼7,500 nucleotides) of PV (18, 30) is translated into one large polyprotein, which is cotranslationally processed by virally encoded proteases 2Apro, 3Cpro, and 3CDpro into mature viral structural and nonstructural proteins (22). The viral proteases have been studied extensively and found to be very specific in polyprotein cleavage; 3Cpro and 3CDpro cleave the polyprotein at glutamine-glycine (Q-G) bonds while the 2Apro cleaves only at tyrosine-glycine (Y-G) bonds (20). The proteases do not cleave every potential cleavage site within the polyprotein; other determinants such as accessibility and context of the cleavage site are also important. Accurate initiation of transcription by RNA polymerase (Pol) II requires the assembly of a multiprotein complex on the core promoter around the mRNA start site (13). The multiprotein complex, consisting of at least seven to eight general transcription factors (GTFs) and RNA Pol II form a preinitiation complex at specific cis-acting elements (promoters) on the DNA template. The most common cis-acting element, the TATA box, is situated approximately 25 nucleotides upstream of the transcription start site. Among the GTFs in the complex, the TATA-binding protein (TBP) has been studied extensively (29). The TBP was first identified through its role in Pol II transcription, where it associates with 13 or 14 TBP-associated factors to form the TFIID complex (34). The unique aspect of TBP is its additional presence in complexes required for RNA Pol I (SL1) and RNA Pol III (TFIIIB) transcription. In both SL1 and TFIIIB complexes, TBP associates with a distinct set of TBP-associated factors (7, 33). Thus, TBP appears to be involved in all three RNA polymerase-mediated transcriptions. TBP has a bipartite structure with a highly conserved C-terminal core domain (amino acids 159 to 339), which folds as a molecular saddle, and is responsible for DNA binding via the concave underside. Additionally, the core also interacts with GTFs and other regulatory proteins via the solvent-exposed convex side. In contrast, the N-terminal region (amino acids 1 to 141) is variable in both length and sequence but is well conserved among vertebrates. It modulates DNA binding by interacting with the core domain and is characterized by a glutamine repeat region (Fig. ​(Fig.1).1). Recent studies have underscored the importance of the TBP N-terminal domain in transcriptional regulation both in yeast and mammalian systems (15, 21). Moreover, deletion of 55 and 96 amino acids from the N-terminal domain of TBP leads to inactivation of TATA-mediated transcription from the U6 small nuclear RNA promoter (24). FIG. 1. Shutoff of RNA polymerase II-mediated transcription does not correlate with 3Cpro-induced cleavage at the 18th glutamine-glycine site in TBP. (A) The domain structure of TBP consisting of the core, N-terminal with the glutamine stretch (Q), and acidic ... Infection of HeLa cells with PV causes a severe decrease in cellular transcription catalyzed by all three cellular RNA polymerases (10). Transcription mediated by RNA polymerase I (Pol I) is inhibited first, at 1 to 2 h postinfection, followed by inhibition of Pol II and Pol III transcription at approximately 3 and 4 h postinfection, respectively. Crawford et al. first showed that PV-induced inhibition of transcription observed in vivo could be recapitulated in vitro (8). Further studies showed that the viral protease 3Cpro alone was responsible for the shutoff of transcription by all three cellular RNA polymerases (36). Recent studies have shown that 3Cpro enters the nucleus in the form of its precursor 3CD (32), which presumably undergoes autocatalysis to generate 3Cpro in the nucleus of infected cells. A primary target of 3Cpro in PV-infected cells was previously identified to be the TATA-binding protein (6). Consistent with this observation, the TFIID complex isolated from PV-infected HeLa cells was transcriptionally inactive in an in vitro reconstituted transcription assay compared to the TFIID isolated from uninfected cells (19). Moreover, purified TBP could be directly cleaved by the purified 3Cpro in vitro, and the addition of purified TBP could completely restore both basal and activated transcription from the TATA and initiator promoters in HeLa cell extracts from PV-infected cells (37). Examination of the human TBP sequence revealed three Q-G sites at positions 12, 18, and 112 (Fig. ​(Fig.1).1). Subsequent in vitro studies using purified components showed that only the 18th Q-G site in TBP could be efficiently cleaved by 3Cpro both in vitro and in vivo (9). To determine if cleavage of TBP at the 18th Q-G bond is responsible for the shutoff of transcription in PV-infected cells, we expressed and purified a recombinant TBP that lacks the N-terminal 18 amino acids (called ΔN18 TBP). If cleavage at the 18th Q-G bond is the primary cause of transcriptional inactivation of TBP, then ΔN18 TBP should not be able to restore transcription in PV-infected cell extracts. We found that ΔN18 TBP was as active as the wild-type (wt) TBP in fully restoring Pol II transcription in PV-infected cell extracts from the adenovirus major late promoter (Ad MLP). We also found that the transcriptional activity of ΔN18 TBP was comparable to that of wt TBP in an in vitro transcription reconstitution assay. Since both genetic and biochemical evidence suggested that 3Cpro was involved in the shutoff of transcription and that TBP was the primary target of 3Cpro, we set out to determine if TBP was being cleaved by 3Cpro at sites other than the 18th Q-G bond. We report here identification of a Q-S site at position 104 to 105 of TBP, which appears to be cleaved by the viral protease 3Cpro. We also demonstrate that an alanine residue at P4 is critical for 3C-mediated cleavage of the 104th Q-S bond. A truncated form of TBP lacking the first 100 amino acids is significantly less active transcriptionally than the wt TBP in vitro. Finally, we demonstrate that a stable HeLa cell line expressing a recombinant TBP (rTBP) resistant to cleavage by the viral proteases is significantly refractive to the shutoff of transcription by poliovirus compared to the control cell line expressing wt TBP. Infection with poliovirus of the HeLa cell line expressing the noncleavable form of TBP shows small plaques and significantly reduced viral RNA synthesis compared to the control TBP cell line, suggesting that a defect in the shutoff of transcription can lead to inefficient replication of the virus.

52 citations


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Journal ArticleDOI
TL;DR: The reemergence of FMD in developed countries that had been disease free for many years is described and the effect that this has had on disease control strategies is described.
Abstract: Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals. The disease was initially described in the 16th century and was the first animal pathogen identified as a virus. Recent FMD outbreaks in developed countries and their significant economic impact have increased the concern of governments worldwide. This review describes the reemergence of FMD in developed countries that had been disease free for many years and the effect that this has had on disease control strategies. The etiologic agent, FMD virus (FMDV), a member of the Picornaviridae family, is examined in detail at the genetic, structural, and biochemical levels and in terms of its antigenic diversity. The virus replication cycle, including virus-receptor interactions as well as unique aspects of virus translation and shutoff of host macromolecular synthesis, is discussed. This information has been the basis for the development of improved protocols to rapidly identify disease outbreaks, to differentiate vaccinated from infected animals, and to begin to identify and test novel vaccine candidates. Furthermore, this knowledge, coupled with the ability to manipulate FMDV genomes at the molecular level, has provided the framework for examination of disease pathogenesis and the development of a more complete understanding of the virus and host factors involved.

1,574 citations

Journal ArticleDOI
01 Mar 2007-Blood
TL;DR: In this paper, gene expression profiles were obtained for 131 peripheral blood samples from pediatric patients with acute infections caused by influenza A virus, Gram-negative (Escherichia coli) or Gram-positive (Staphylococcus aureus and Streptococcus pneumoniae) bacteria.

472 citations

Journal ArticleDOI
TL;DR: This review introduces the progress of research on AMPs comprehensively and systematically, including their classification, mechanism of action, design methods, environmental factors affecting their activity, application status, prospects in various fields and problems to be solved.
Abstract: Antimicrobial peptides (AMPs) are a class of small peptides that widely exist in nature and they are an important part of the innate immune system of different organisms. AMPs have a wide range of inhibitory effects against bacteria, fungi, parasites and viruses. The emergence of antibiotic-resistant microorganisms and the increasing of concerns about the use of antibiotics resulted in the development of AMPs, which have a good application prospect in medicine, food, animal husbandry, agriculture and aquaculture. This review introduces the progress of research on AMPs comprehensively and systematically, including their classification, mechanism of action, design methods, environmental factors affecting their activity, application status, prospects in various fields and problems to be solved. The research progress on antivirus peptides, especially anti-coronavirus (COVID-19) peptides, has been introduced given the COVID-19 pandemic worldwide in 2020.

469 citations

Journal ArticleDOI
TL;DR: expression of nsp1, the most N-terminal gene 1 protein, prevented Sendai virus-induced endogenous IFN-β mRNA accumulation without inhibiting dimerization of IFN regulatory factor 3, a protein that is essential for activation of theIFN- β promoter.
Abstract: Severe acute respiratory syndrome (SARS) coronavirus (SCoV) causes a recently emerged human disease associated with pneumonia. The 5′ end two-thirds of the single-stranded positive-sense viral genomic RNA, gene 1, encodes 16 mature proteins. Expression of nsp1, the most N-terminal gene 1 protein, prevented Sendai virus-induced endogenous IFN-β mRNA accumulation without inhibiting dimerization of IFN regulatory factor 3, a protein that is essential for activation of the IFN-β promoter. Furthermore, nsp1 expression promoted degradation of expressed RNA transcripts and host endogenous mRNAs, leading to a strong host protein synthesis inhibition. SCoV replication also promoted degradation of expressed RNA transcripts and host mRNAs, suggesting that nsp1 exerted its mRNA destabilization function in infected cells. In contrast to nsp1-induced mRNA destablization, no degradation of the 28S and 18S rRNAs occurred in either nsp1-expressing cells or SCoV-infected cells. These data suggested that, in infected cells, nsp1 promotes host mRNA degradation and thereby suppresses host gene expression, including proteins involved in host innate immune functions. SCoV nsp1-mediated promotion of host mRNA degradation may play an important role in SCoV pathogenesis.

401 citations

Journal ArticleDOI
TL;DR: It is demonstrated that SARS-CoV nsp1 suppressed host innate immune functions, including type I IFN expression, in infected cells and suggested that Sars- CoV nSp1 most probably plays a critical role in SARS -CoV virulence.
Abstract: The severe acute respiratory syndrome coronavirus (SARS-CoV) nsp1 protein has unique biological functions that have not been described in the viral proteins of any RNA viruses; expressed SARS-CoV nsp1 protein has been found to suppress host gene expression by promoting host mRNA degradation and inhibiting translation. We generated an nsp1 mutant (nsp1-mt) that neither promoted host mRNA degradation nor suppressed host protein synthesis in expressing cells. Both a SARS-CoV mutant virus, encoding the nsp1-mt protein (SARS-CoV-mt), and a wild-type virus (SARS-CoV-WT) replicated efficiently and exhibited similar one-step growth kinetics in susceptible cells. Both viruses accumulated similar amounts of virus-specific mRNAs and nsp1 protein in infected cells, whereas the amounts of endogenous host mRNAs were clearly higher in SARS-CoV-mt-infected cells than in SARS-CoV-WT-infected cells, in both the presence and absence of actinomycin D. Further, SARS-CoV-WT replication strongly inhibited host protein synthesis, whereas host protein synthesis inhibition in SARS-CoV-mt-infected cells was not as efficient as in SARS-CoV-WT-infected cells. These data revealed that nsp1 indeed promoted host mRNA degradation and contributed to host protein translation inhibition in infected cells. Notably, SARS-CoV-mt infection, but not SARS-CoV-WT infection, induced high levels of beta interferon (IFN) mRNA accumulation and high titers of type I IFN production. These data demonstrated that SARS-CoV nsp1 suppressed host innate immune functions, including type I IFN expression, in infected cells and suggested that SARS-CoV nsp1 most probably plays a critical role in SARS-CoV virulence.

396 citations