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排序方式: 共有398条查询结果,搜索用时 8 毫秒
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Natasha Wood Tanmoy Bhattacharya Brandon F. Keele Elena Giorgi Michael Liu Brian Gaschen Marcus Daniels Guido Ferrari Barton F. Haynes Andrew McMichael George M. Shaw Beatrice H. Hahn Bette Korber Cathal Seoighe 《PLoS pathogens》2009,5(5)
The pattern of viral diversification in newly infected individuals provides information about the host environment and immune responses typically experienced by the newly transmitted virus. For example, sites that tend to evolve rapidly across multiple early-infection patients could be involved in enabling escape from common early immune responses, could represent adaptation for rapid growth in a newly infected host, or could represent reversion from less fit forms of the virus that were selected for immune escape in previous hosts. Here we investigated the diversification of HIV-1 env coding sequences in 81 very early B subtype infections previously shown to have resulted from transmission or expansion of single viruses (n = 78) or two closely related viruses (n = 3). In these cases, the sequence of the infecting virus can be estimated accurately, enabling inference of both the direction of substitutions as well as distinction between insertion and deletion events. By integrating information across multiple acutely infected hosts, we find evidence of adaptive evolution of HIV-1 env and identify a subset of codon sites that diversified more rapidly than can be explained by a model of neutral evolution. Of 24 such rapidly diversifying sites, 14 were either i) clustered and embedded in CTL epitopes that were verified experimentally or predicted based on the individual''s HLA or ii) in a nucleotide context indicative of APOBEC-mediated G-to-A substitutions, despite having excluded heavily hypermutated sequences prior to the analysis. In several cases, a rapidly evolving site was embedded both in an APOBEC motif and in a CTL epitope, suggesting that APOBEC may facilitate early immune escape. Ten rapidly diversifying sites could not be explained by CTL escape or APOBEC hypermutation, including the most frequently mutated site, in the fusion peptide of gp41. We also examined the distribution, extent, and sequence context of insertions and deletions, and we provide evidence that the length variation seen in hypervariable loop regions of the envelope glycoprotein is a consequence of selection and not of mutational hotspots. Our results provide a detailed view of the process of diversification of HIV-1 following transmission, highlighting the role of CTL escape and hypermutation in shaping viral evolution during the establishment of new infections. 相似文献
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Kovats RS Campbell-Lendrum DH McMichael AJ Woodward A Cox JS 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2001,356(1411):1057-1068
The world's climate appears now to be changing at an unprecedented rate. Shifts in the distribution and behaviour of insect and bird species indicate that biological systems are already responding to this change. It is well established that climate is an important determinant of the spatial and temporal distribution of vectors and pathogens. In theory, a change in climate would be expected to cause changes in the geographical range, seasonality (intra-annual variability), and in the incidence rate (with or without changes in geographical or seasonal patterns). The detection and then attribution of such changes to climate change is an emerging task for scientists. We discuss the evidence required to attribute changes in disease and vectors to the early effects of anthropogenic climate change. The literature to date indicates that there is a lack of strong evidence of the impact of climate change on vector-borne diseases (i.e. malaria, dengue, leishmaniasis, tick-borne diseases). New approaches to monitoring, such as frequent and long-term sampling along transects to monitor the full latitudinal and altitudinal range of specific vector species, are necessary in order to provide convincing direct evidence of climate change effects. There is a need to reassess the appropriate levels of evidence, including dealing with the uncertainties attached to detecting the health impacts of global change. 相似文献
4.
McMichael JC 《Microbes and infection / Institut Pasteur》2000,2(5):561-568
Moraxella catarrhalis is a major cause of otitis media and respiratory disease. Vaccine development is at the antigen identification stage. This review examines the more promising antigens, including the 200K protein, the hemagglutinins, the lactoferrin-binding proteins, the UspA proteins, the CopB protein, the transferrin-binding proteins, the CD protein, the E protein and lipooligosaccharide conjugates. Clinical testing of some of these antigens should begin soon. 相似文献
5.
Moffat JF McMichael MA Leisenfelder SA Taylor SL 《Biochimica et biophysica acta》2004,1697(1-2):225-231
Herpesviruses utilize viral and cellular kinases for replication, and these mediate essential functions that are important for viral pathogenesis. Elucidating the roles of kinases in herpesvirus infections may highlight virus-host interactions that are possible targets for kinase inhibitors with antiviral activity. Varicella zoster virus (VZV) encodes two kinases that phosphorylate viral proteins involved in regulation, assembly, and virulence. VZV infection also induces the activity of host cell cyclin-dependent kinases (cdk4 and cdk2) in nondividing cells, causing a disregulation of the cell cycle. Roscovitine and Purvalanol, kinase inhibitors that target cdks, prevent VZV replication at concentrations with few cytotoxic effects. Cdk inhibitors therefore have potential as antivirals that may extend to a broad range of viruses and have the added advantage that resistance does not arise easily. 相似文献
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Class I molecules of the major histocompatibility complex (MHC) bind peptides derived from cytoplasmic proteins. Comparison of over 100 such peptides reveals the importance of the carboxy-terminal residue in selective binding. Recent evidence implicates the proteases and transporters of the processing pathway in providing peptides with the correct residues at the carboxyl terminus. 相似文献
8.
Rates and patterns of evolution in partial sequences of five mitochondrial
genes (cytochrome b, ATPase 6, NADH dehydrogenase subunit 5, tRNA(Glu), and
the control region) were compared among taxa in the passerine bird genera
Fringilla and Carduelis. Rates of divergence do not vary significantly
among genes, even in comparisons with the control region. Rate variation
among lineages is significant only for the control region and NADH
dehydrogenase subunit 5, and patterns of variation are consistent with the
expectations of neutral theory. Base composition is biased in all genes but
is stationary among lineages, and there is evidence for directional
mutation pressure only in the control region. Despite these similarities,
patterns of substitution differ among genes, consistent with alternative
regimes of selective constraint. Rates of nonsynonymous substitution are
higher in NADH dehydrogenase subunit 5 than in other protein-coding genes,
and transitions exist in elevated proportions relative to transversions.
Transitions appear to accumulate linearly with time in tRNA(Glu), and
despite exhibiting the highest overall rate of divergence among species,
there are no transversional changes in this gene. Finally, for resolving
phylogenetic relationships among Fringilla taxa, the combined
protein-coding data are broadly similar to those of the control region in
terms of phylogenetic informativeness and statistical support.
相似文献
9.
Antigen-Specific Expansion of Cytotoxic T Lymphocytes in Acute Measles Virus Infection 总被引:3,自引:3,他引:3 下载免费PDF全文
Juthathip Mongkolsapaya Assan Jaye Margaret F. C. Callan Albert F. Magnusen Andrew J. McMichael Hilton C. Whittle 《Journal of virology》1999,73(1):67-71
Skewing of the T-cell receptor repertoire of CD8+ T cells has been shown in some persistent infections with viruses, such as human immunodeficiency virus, simian immunodeficiency virus, and Epstein-Barr virus. We have demonstrated that similar distortions also occur in nonpersistent measles virus infection. In addition, two of four children immunized with live, attenuated measles virus showed larger and more persistent CD8+ T-cell expansions than their naturally infected counterparts. The expanded lymphocyte populations were monoclonal or oligoclonal and lysed target cells infected with recombinant vaccinia virus expressing measles virus protein. These results demonstrate that the expansions of CD8+ T lymphocytes are antigen driven. 相似文献
10.