oalib
Search Results: 1 - 10 of 100 matches for " "
All listed articles are free for downloading (OA Articles)
Page 1 /100
Display every page Item
HIV-1 evolution, drug resistance, and host genetics: The Indian scenario
U Shankarkumar, A Pawar, K Ghosh
Virus Adaptation and Treatment , 2009, DOI: http://dx.doi.org/10.2147/VAAT.S4974
Abstract: lution, drug resistance, and host genetics: The Indian scenario Review (4933) Total Article Views Authors: U Shankarkumar, A Pawar, K Ghosh Published Date March 2009 Volume 2009:1 Pages 1 - 4 DOI: http://dx.doi.org/10.2147/VAAT.S4974 U Shankarkumar, A Pawar, K Ghosh National Institute of Immunohaematology (ICMR), KEM Hospital, Parel, Mumbai, Maharashtra, India Abstract: A regimen with varied side effects and compliance is of paramount importance to prevent viral drug resistance. Most of the drug-resistance studies, as well as interpretation algorithms, are based on sequence data from HIV-1 subtype B viruses. Increased resistance to antiretroviral drugs leads to poor prognosis by restricting treatment options. Due to suboptimal adherence to antiretroviral therapy there is an emergence of drug-resistant HIV-1 strains. The other factors responsible for this viral evolution are antiretroviral drug types and host genetics, especially major histocompatibility complex (MHC). Both primary and secondary drug resistances occur due to mutations in specific epitopes of viral protein regions which may influence the T cell recognition by immune system through MHC Class I and class II alleles. Mutations in viral epitopes enable the virus to escape the immune system. New drugs under clinical trials are being added but their exorbitant costs limit their access in developing countries. Thus the environmental consequences and, the impact of both viral and host genetic variations on the therapy in persons infected with HIV-1 clade C from India need to be determined.
HIV-1 evolution, drug resistance, and host genetics: The Indian scenario  [cached]
U Shankarkumar,A Pawar,K Ghosh
Virus Adaptation and Treatment , 2009,
Abstract: U Shankarkumar, A Pawar, K GhoshNational Institute of Immunohaematology (ICMR), KEM Hospital, Parel, Mumbai, Maharashtra, IndiaAbstract: A regimen with varied side effects and compliance is of paramount importance to prevent viral drug resistance. Most of the drug-resistance studies, as well as interpretation algorithms, are based on sequence data from HIV-1 subtype B viruses. Increased resistance to antiretroviral drugs leads to poor prognosis by restricting treatment options. Due to suboptimal adherence to antiretroviral therapy there is an emergence of drug-resistant HIV-1 strains. The other factors responsible for this viral evolution are antiretroviral drug types and host genetics, especially major histocompatibility complex (MHC). Both primary and secondary drug resistances occur due to mutations in specific epitopes of viral protein regions which may influence the T cell recognition by immune system through MHC Class I and class II alleles. Mutations in viral epitopes enable the virus to escape the immune system. New drugs under clinical trials are being added but their exorbitant costs limit their access in developing countries. Thus the environmental consequences and, the impact of both viral and host genetic variations on the therapy in persons infected with HIV-1 clade C from India need to be determined.Keywords: HIV-1 C drug resistance, virus adaptation, HARRT, India
The Evolution and Genetics of Virus Host Shifts  [PDF]
Ben Longdon ,Michael A. Brockhurst,Colin A. Russell,John J. Welch,Francis M. Jiggins
PLOS Pathogens , 2014, DOI: doi/10.1371/journal.ppat.1004395
Abstract: Emerging viral diseases are often the product of a host shift, where a pathogen jumps from its original host into a novel species. Phylogenetic studies show that host shifts are a frequent event in the evolution of most pathogens, but why pathogens successfully jump between some host species but not others is only just becoming clear. The susceptibility of potential new hosts can vary enormously, with close relatives of the natural host typically being the most susceptible. Often, pathogens must adapt to successfully infect a novel host, for example by evolving to use different cell surface receptors, to escape the immune response, or to ensure they are transmitted by the new host. In viruses there are often limited molecular solutions to achieve this, and the same sequence changes are often seen each time a virus infects a particular host. These changes may come at a cost to other aspects of the pathogen's fitness, and this may sometimes prevent host shifts from occurring. Here we examine how these evolutionary factors affect patterns of host shifts and disease emergence.
HIV: master of the host cell
Christopher W Arendt, Dan R Littman
Genome Biology , 2001, DOI: 10.1186/gb-2001-2-11-reviews1030
Abstract: The human immunodeficiency virus (HIV) infects CD4+ T lymphocytes and macrophages, eventually inducing the depletion of CD4+ T cells, which is the defining feature of the acquired immune deficiency syndrome (AIDS). It is not clear precisely how the virus exploits the host cell to maximize viral particle production, but evidence is accumulating that HIV activates the cellular transcription machinery to achieve this aim. While biochemical approaches have been extensively employed to study the intracellular response to HIV infection, the advent of lymphocyte microarrays has provided a powerful new tool to help illuminate the extensive effects of HIV on host-cell transcriptional responses.Biochemical studies have demonstrated that HIV is capable of modulating a variety of signal transduction pathways in the host cell at multiple stages in the infection process, beginning at entry when it engages two transmembrane receptors, CD4 plus either of the chemokine receptors CCR5 or CXCR4, thereby activating intracellular protein tyrosine kinases [1]. Indication that HIV gene products influence signaling processes in host cells also comes from analyses of transgenic mice that express portions of the HIV genome and display a variety of abnormalities, ranging from altered T-cell maturation [2] to the development of a systemic disease similar to AIDS [3]. Because the long terminal repeats (LTRs) of HIV contain consensus recognition motifs for the NF-κB and NFAT families of transcriptional transactivators, it has been speculated that HIV may have evolved mechanisms to potentiate cellular activation pathways, thereby augmenting expression of its own genome. Until now, however, there has been limited understanding of how HIV exerts control over specific transactivation responses of the host cell.Because HIV employs host factors that are vital for its replication cycle, the virus may have evolved means of modulating their expression levels during infection, so as to favor its own repli
Predominant Role of Host Genetics in Controlling the Composition of Gut Microbiota  [PDF]
Zaruhi A. Khachatryan, Zhanna A. Ktsoyan, Gayane P. Manukyan, Denise Kelly, Karine A. Ghazaryan, Rustam I. Aminov
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0003064
Abstract: Background The human gastrointestinal tract is inhabited by a very diverse symbiotic microbiota, the composition of which depends on host genetics and the environment. Several studies suggested that the host genetics may influence the composition of gut microbiota but no genes involved in host control were proposed. We investigated the effects of the wild type and mutated alleles of the gene, which encodes the protein called pyrin, one of the regulators of innate immunity, on the composition of gut commensal bacteria. Mutations in MEFV lead to the autoinflammatory disorder, familial Mediterranean fever (FMF, MIM249100), which is characterized by recurrent self-resolving attacks of fever and polyserositis, with no clinical signs of disease in remission. Methodology/Principal Findings A total of 19 FMF patients and eight healthy individuals were genotyped for mutations in the MEFV gene and gut bacterial diversity was assessed by sequencing 16S rRNA gene libraries and FISH analysis. These analyses demonstrated significant changes in bacterial community structure in FMF characterized by depletion of total numbers of bacteria, loss of diversity, and major shifts in bacterial populations within the Bacteroidetes, Firmicutes and Proteobacteria phyla in attack. In remission with no clinical signs of disease, bacterial diversity values were comparable with control but still, the bacterial composition was substantially deviant from the norm. Discriminant function analyses of gut bacterial diversity revealed highly specific, well-separated and distinct grouping, which depended on the allele carrier status of the host. Conclusions/Significance This is the first report that clearly establishes the link between the host genotype and the corresponding shifts in the gut microbiota (the latter confirmed by two independent techniques). It suggests that the host genetics is a key factor in host-microbe interaction determining a specific profile of commensal microbiota in the human gut.
The Role of Host Genetics in Susceptibility to Influenza: A?Systematic Review  [PDF]
Peter Horby, Nhu Y. Nguyen, Sarah J. Dunstan, J. Kenneth Baillie
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0033180
Abstract: Background The World Health Organization has identified studies of the role of host genetics on susceptibility to severe influenza as a priority. A systematic review was conducted to summarize the current state of evidence on the role of host genetics in susceptibility to influenza (PROSPERO registration number: CRD42011001380). Methods and Findings PubMed, Web of Science, the Cochrane Library, and OpenSIGLE were searched using a pre-defined strategy for all entries up to the date of the search. Two reviewers independently screened the title and abstract of 1,371 unique articles, and 72 full text publications were selected for inclusion. Mouse models clearly demonstrate that host genetics plays a critical role in susceptibility to a range of human and avian influenza viruses. The Mx genes encoding interferon inducible proteins are the best studied but their relevance to susceptibility in humans is unknown. Although the MxA gene should be considered a candidate gene for further study in humans, over 100 other candidate genes have been proposed. There are however no data associating any of these candidate genes to susceptibility in humans, with the only published study in humans being under-powered. One genealogy study presents moderate evidence of a heritable component to the risk of influenza-associated death, and while the marked familial aggregation of H5N1 cases is suggestive of host genetic factors, this remains unproven. Conclusion The fundamental question “Is susceptibility to severe influenza in humans heritable?” remains unanswered. Not because of a lack of genotyping or analytic tools, nor because of insufficient severe influenza cases, but because of the absence of a coordinated effort to define and assemble cohorts of cases. The recent pandemic and the ongoing epizootic of H5N1 both represent rapidly closing windows of opportunity to increase understanding of the pathogenesis of severe influenza through multi-national host genetic studies.
HIV–1 Dynamics: A Reappraisal of Host and Viral Factors, as well as Methodological Issues  [PDF]
Heather A. Prentice,Jianming Tang
Viruses , 2012, DOI: 10.3390/v4102080
Abstract: The dynamics of HIV–1 viremia is a complex and evolving landscape with clinical and epidemiological (public health) implications. Most studies have relied on the use of set–point viral load (VL) as a readily available proxy of viral dynamics to assess host and viral correlates. This review highlights recent findings from population–based studies of set–point VL, focusing primarily on robust data related to host genetics. A comprehensive understanding of viral dynamics will clearly need to consider both host and viral characteristics, with close attention to (i) the timing of VL measurements, (ii) the biology of viral evolution, (iii) compartments of active viral replication, (iv) the transmission source partner as the immediate past microenvironment, and (v) proper application of statistical models.
Murine Gut Microbiota Is Defined by Host Genetics and Modulates Variation of Metabolic Traits  [PDF]
Autumn M. McKnite, Maria Elisa Perez-Munoz, Lu Lu, Evan G. Williams, Simon Brewer, Pénélope A. Andreux, John W. M. Bastiaansen, Xusheng Wang, Stephen D. Kachman, Johan Auwerx, Robert W. Williams, Andrew K. Benson, Daniel A. Peterson, Daniel C. Ciobanu
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0039191
Abstract: The gastrointestinal tract harbors a complex and diverse microbiota that has an important role in host metabolism. Microbial diversity is influenced by a combination of environmental and host genetic factors and is associated with several polygenic diseases. In this study we combined next-generation sequencing, genetic mapping, and a set of physiological traits of the BXD mouse population to explore genetic factors that explain differences in gut microbiota and its impact on metabolic traits. Molecular profiling of the gut microbiota revealed important quantitative differences in microbial composition among BXD strains. These differences in gut microbial composition are influenced by host-genetics, which is complex and involves many loci. Linkage analysis defined Quantitative Trait Loci (QTLs) restricted to a particular taxon, branch or that influenced the variation of taxa across phyla. Gene expression within the gastrointestinal tract and sequence analysis of the parental genomes in the QTL regions uncovered candidate genes with potential to alter gut immunological profiles and impact the balance between gut microbial communities. A QTL region on Chr 4 that overlaps several interferon genes modulates the population of Bacteroides, and potentially Bacteroidetes and Firmicutes–the predominant BXD gut phyla. Irak4, a signaling molecule in the Toll-like receptor pathways is a candidate for the QTL on Chr15 that modulates Rikenellaceae, whereas Tgfb3, a cytokine modulating the barrier function of the intestine and tolerance to commensal bacteria, overlaps a QTL on Chr 12 that influence Prevotellaceae. Relationships between gut microflora, morphological and metabolic traits were uncovered, some potentially a result of common genetic sources of variation.
Genetics and Genomics of Infectious Diseases: advancing our understanding of host/pathogens and their interactions
Ninghan Yang, Martin L Hibberd
Genome Medicine , 2009, DOI: 10.1186/gm52
Abstract: The Genetics and Genomics of Infectious Diseases conference http://www.nature.com/natureconferences/ggid2009/index.html webcite gathered researchers from diverse areas of expertise to further our understanding of infectious diseases, integrating knowledge of different aspects of pathogen and host biology to form a holistic picture. It was the first time that two major genetic societies, the American Society of Human Genetics and the Human Genome Organisation, have collaborated to bring together scientists interested in different but interdependent aspects of infectious diseases. The conference was also co-hosted by the Nature Publishing Group, with support from the World Health Organization and the Ministry of Health of Singapore. The meeting attracted more than 250 participants, and around 30 talks and over 40 posters were presented, with four workshops given by biotechnology companies.The meeting was able to integrate the diverse fields of human responses to infectious disease, microbe discovery, epidemiology, drug discovery and others by focusing on high-throughput genomic technologies. It was remarkable how this provided a common language to all the participants and allowed deep understanding of areas outside each individual's usual expertise.Some of the more novel insights came from the direct application of these technologies by groups that might not see themselves as traditional microbiologists. For example, Rotem Sorek (Weizmann Institute of Science, Rehovot, Israel) described a novel method of antimicrobial discovery, following their realization that cloning gaps in microbial sequencing undertakings may be due to genes that kill the cloning microorganism, Escherichia coli. It was fascinating to hear the innovative perspective given to a common phenomenon that is not given much attention in sequencing and that could potentially be turned to high-throughput screening for antimicrobials through microfluidics. Daniel Falush (University College, Dublin, Ireland)
Variable effect of co-infection on the HIV infectivity: Within-host dynamics and epidemiological significance
Diego F Cuadros, Gisela García-Ramos
Theoretical Biology and Medical Modelling , 2012, DOI: 10.1186/1742-4682-9-9
Abstract: We developed a within-host deterministic differential equation model to describe the dynamics of HIV and malaria infections, and evaluated the effect of variations in the viral replicative capacity on the VL burden generated by co-infection. These variations were then evaluated at population level by implementing a between-host model in which the relationship between VL and the probability of HIV transmission per sexual contact was used as the within-host and between-host interface.Our within-host results indicated that the combination of parameters generating low spVL were unable to produce a substantial increase in the VL in response to co-infection. Conversely, larger spVL were associated with substantially larger increments in the VL. In accordance, the between-host model indicated that co-infection had a negligible impact in populations where the virus had low replicative capacity, reflected in low spVL. Similarly, the impact of co-infection increased as the spVL of the population increased.Our results indicated that variations in the viral replicative capacity would influence the effect of co-infection on the VL. Therefore, viral factors could play an important role driving several virus-related processes such as the increment of the VL induced by co-infections. These results raise the possibility that biological differences could alter the effect of co-infection and underscore the importance of identifying these factors for the implementation of control interventions focused on co-infection.At present, the role of viral genetic factors in the HIV epidemic is poorly understood. Many different HIV genetic subtypes circulate worldwide as well as their recombinant forms [1]. Moreover, there is a substantial variation in the length of the asymptomatic (chronic) phase of HIV infection, ranging from a few months to many years. This variation has been correlated with the so-called set point viral load (spVL), defined as the measure of the HIV concentration in blood d
Page 1 /100
Display every page Item


Home
Copyright © 2008-2017 Open Access Library. All rights reserved.