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Author

Alok Chakrabarti

Bio: Alok Chakrabarti is an academic researcher from Variable Energy Cyclotron Centre. The author has contributed to research in topics: Beam (structure) & Ion beam. The author has an hindex of 20, co-authored 153 publications receiving 1497 citations. Previous affiliations of Alok Chakrabarti include Homi Bhabha National Institute & University of California, Los Angeles.


Papers
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Journal ArticleDOI
TL;DR: Although the sequences of NA CT and TMD per se are not absolutely essential for the virus life cycle, specific amino acid sequences play a critical role in providing structural stability, enzyme activity, and lipid raft association of NA.
Abstract: Influenza virus neuraminidase (NA), a type II transmembrane glycoprotein, possesses receptor-destroying activity and thereby facilitates virus release from the cell surface. Among the influenza A viruses, both the cytoplasmic tail (CT) and transmembrane domain (TMD) amino acid sequences of NA are highly conserved, yet their function(s) in virus biology remains unknown. To investigate the role of amino acid sequences of the CT and TMD on the virus life cycle, we systematically mutagenized the entire CT and TMD of NA by converting two to five contiguous amino acids to alanine. In addition, we also made two chimeric NA by replacing the CT proximal one-third amino acids of the NA TMD [NA(1T2N)NA] and the entire NA TMD (NATRNA) with that of human transferrin receptor (TR) (a type II transmembrane glycoprotein). We rescued transfectant mutant viruses by reverse genetics and examined their phenotypes. Our results show that all mutated and chimeric NAs could be rescued into transfectant viruses. Different mutants showed pleiotropic effects on virus growth and replication. Some mutants (NA2A5, NA3A7, and NA4A10) had little effect on virus growth while others (NA3A2, NA5A27, and NA5A31) produced about 50- to 100-fold-less infectious virus and still some others (NA5A14, NA4A19, and NA4A23) exhibited an intermediate phenotype. In general, mutations towards the ectodomain-proximal sequences of TMD progressively caused reduction in NA enzyme activity, affected lipid raft association, and attenuated virus growth. Electron microscopic analysis showed that these mutant viruses remained aggregated and bound to infected cell surfaces and could be released from the infected cells by bacterial NA treatment. Moreover, viruses containing mutations in the extreme N terminus of the CT (NA3A2) as well as chimeric NA containing the TMD replaced partially [NA(1T2N)NA] or fully (NATRNA) with TR TMD caused reduction in virus growth and exhibited the morphological phenotype of elongated particles. These results show that although the sequences of NA CT and TMD per se are not absolutely essential for the virus life cycle, specific amino acid sequences play a critical role in providing structural stability, enzyme activity, and lipid raft association of NA. In addition, aberrant morphogenesis including elongated particle formation of some mutant viruses indicates the involvement of NA in virus morphogenesis and budding.

121 citations

Journal ArticleDOI
TL;DR: Continuous monitoring is strongly advisable, not only to the newly infected individuals, but also to those recovered individuals who were infected by SARS-CoV-2 as re-infection may lead to the selection of escape mutants and subsequent dissemination to the population.
Abstract: The last century has witnessed several assaults from RNA viruses, resulting in millions of death throughout the world. The 21st century appears no longer an exception, with the trend continued with escalated fear of SARS coronavirus in 2002 and further concern of influenza H5N1 in 2003. A novel influenza virus created the first pandemic of the 21st century, the pandemic flu in 2009 preceded with the emergence of another deadly virus, MERS-CoV in 2012. A novel coronavirus "SARS-CoV-2" (and the disease COVID-19) emerged suddenly, causing a rapid outbreak with a moderate case fatality rate. This virus is continuing to cause health care providers grave concern due to the lack of any existing immunity in the human population, indicating their novelty and lack of previous exposure. The big question is whether this novel virus will be establishing itself in an endemic form or will it eventually die out? Endemic viruses during circulation may acquire mutations to infect naive, as well as individual with pre-existing immunity. Continuous monitoring is strongly advisable, not only to the newly infected individuals, but also to those recovered individuals who were infected by SARS-CoV-2 as re-infection may lead to the selection of escape mutants and subsequent dissemination to the population.

108 citations

Journal ArticleDOI
TL;DR: In this paper, it has been shown that defects govern the room temperature magnetic property of nanocrystalline ZnO, which exhibits a paramagnetic behavior at room temperature but becomes ferromagnetic once oxygen defects are introduced in it.

62 citations

Journal ArticleDOI
16 Nov 2009-PLOS ONE
TL;DR: Overall, the study is indicative of a possible endemicity in the eastern and northeastern parts of the country, demanding active surveillance specifically in view of the critical mutations that have been observed in the influenza A H5N1 viruses.
Abstract: Widespread infection of highly pathogenic avian influenza A H5N1 was reported from backyard and commercial poultry in West Bengal (WB), an eastern state of India in early 2008. Infection gradually spread to Tripura, Assam and Sikkim, the northeastern states, with 70 outbreaks reported between January 2008 and May 2009. Whole genome sequence analysis of three isolates from WB, one isolate from Tripura along with the analysis of hemagglutinin (HA) and neuraminidase (NA) genes of 17 other isolates was performed during this study. In the HA gene phylogenetic tree, all the 2008-09 Indian isolates belonged to EMA3 sublineage of clade 2.2. The closest phylogenetic relationship was found to be with the 2007-09 isolates from Bangladesh and not with the earlier 2006 and 2007 Indian isolates implying a third introduction into the country. The receptor-binding pocket of HA1 of two isolates from WB showed S221P mutation, one of the markers predicted to be associated with human receptor specificity. Two substitutions E119A (2 isolates of WB) and N294S (2 other isolates of WB) known to confer resistance to NA inhibitors were observed in the active site of neuraminidase. Several additional mutations were observed within the 2008-09 Indian isolates indicating genetic diversification. Overall, the study is indicative of a possible endemicity in the eastern and northeastern parts of the country, demanding active surveillance specifically in view of the critical mutations that have been observed in the influenza A H5N1 viruses.

59 citations

Journal ArticleDOI
05 Jun 2013-Virology
TL;DR: A review of the reports since the discovery of PB1F2 suggests a multifunctional role for this protein that includes a proapoptotic function in immune cells and an ability to cause increased pathogenesis in animal models by dysregulating cytokines and inducing inflammation.

58 citations


Cited by
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Journal ArticleDOI
15 Mar 2011-Virology
TL;DR: This review investigates the latest research on influenza virus budding in an attempt to provide a step-by-step analysis of the assembly and budding processes for influenza viruses.

613 citations

Journal ArticleDOI
17 Sep 2010-Cell
TL;DR: It is shown that M2 localizes to the neck of budding virions and that mutation of the M2 amphipathic helix results in failure of the virus to undergo membrane scission and virion release, suggesting that M1 mediates the final steps of budding for influenza viruses, bypassing the need for host ESCRT proteins.

490 citations

Journal ArticleDOI
TL;DR: It is shown that the interferon-induced protein viperin inhibits influenza A virus release from the plasma membrane of infected cells, suggesting that targeting the release stage of the life cycle may affect the replication of many enveloped viruses.

451 citations

Journal ArticleDOI
TL;DR: Influenza viruses are causative agents of an acute febrile respiratory disease called influenza and belong to the Orthomyxoviridae family and are enveloped, usually spherical and bud from the plasma membrane (more specifically, the apical plasma membrane of polarized epithelial cells).

410 citations

Posted Content
TL;DR: In this article, a stochastic nonlinear continuum theory is proposed to describe the morphological evolution of amorphous surfaces eroded by ion bombardment, and it is shown that for short time scales, where the effect of nonlinear terms is negligible, the continuum theory predicts ripple formation.
Abstract: We derive a stochastic nonlinear continuum theory to describe the morphological evolution of amorphous surfaces eroded by ion bombardment. Starting from Sigmund's theory of sputter erosion, we calculate the coefficients appearing in the continuum equation in terms of the physical parameters characterizing the sputtering process. We analyze the morphological features predicted by the continuum theory, comparing them with the experimentally reported morphologies. We show that for short time scales, where the effect of nonlinear terms is negligible, the continuum theory predicts ripple formation. We demonstrate that in addition to relaxation by thermal surface diffusion, the sputtering process can also contribute to the smoothing mechanisms shaping the surface morphology. We explicitly calculate an effective surface diffusion constant characterizing this smoothing effect, and show that it is responsible for the low temperature ripple formation observed in various experiments. At long time scales the nonlinear terms dominate the evolution of the surface morphology. The nonlinear terms lead to the stabilization of the ripple wavelength and we show that, depending on the experimental parameters such as angle of incidence and ion energy, different morphologies can be observed: asymptotically, sputter eroded surfaces could undergo kinetic roughening, or can display novel ordered structures with rotated ripples. Finally, we discuss in detail the existing experimental support for the proposed theory, and uncover novel features of the surface morphology and evolution, that could be directly tested experimentally.

385 citations