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Genotypic distribution of HHV-8 in AIDS individuals without and with Kaposi sarcoma : Is genotype B associated with better prognosis of AIDS-KS?

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      Abstract

      AIDS-associated Kaposi's sarcoma (AIDS-KS) caused by human herpes virus 8 (HHV-8) is the most severe and resistant form of KS tumor. Our aim was to verify whether there is an association between HHV-8 variability and development of AIDS-KS in Brazil by comparing the HHV-8 variability between individuals without and with KS. Saliva samples and blood, when available, were analyzed by polymerase chain reaction (PCR) techniques for detection of the fragments of ORF K1 of HHV-8, which were then genotyped and analyzed regarding the genetic variability. Our study described 106 positive cases for HHV-8 in the saliva from 751 AIDS patients without previous KS. In addition, we performed a phylogenetic analysis of HHV-8 in 34 of the 106 AIDS patients without KS and in 33 of the 37 patients with active KS. The distribution of HHV-8 genotypes A, B, C, and F in AIDS individuals was indistinguishable by comparing non-KS and KS groups, as well as regarding ethnicity. Considering the KS group, genotype B was associated with better prognosis of KS tumor. Interestingly, we found a particular profile of diversity within clade C and 2 recombinant patterns of HHV-8 in the saliva of AIDS individuals without KS. We emphasize the need to achieve standard genotyping protocol for ORF K1 amplification, thus allowing for substantial detection of HHV-8 variants. Our findings can shed light on the role of HHV-8 variability in the pathogenesis of AIDS-KS.

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      Most cited references 46

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      MUSCLE: multiple sequence alignment with high accuracy and high throughput.

       Robert Edgar (2004)
      We describe MUSCLE, a new computer program for creating multiple alignments of protein sequences. Elements of the algorithm include fast distance estimation using kmer counting, progressive alignment using a new profile function we call the log-expectation score, and refinement using tree-dependent restricted partitioning. The speed and accuracy of MUSCLE are compared with T-Coffee, MAFFT and CLUSTALW on four test sets of reference alignments: BAliBASE, SABmark, SMART and a new benchmark, PREFAB. MUSCLE achieves the highest, or joint highest, rank in accuracy on each of these sets. Without refinement, MUSCLE achieves average accuracy statistically indistinguishable from T-Coffee and MAFFT, and is the fastest of the tested methods for large numbers of sequences, aligning 5000 sequences of average length 350 in 7 min on a current desktop computer. The MUSCLE program, source code and PREFAB test data are freely available at http://www.drive5. com/muscle.
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        MAFFT: a novel method for rapid multiple sequence alignment based on fast Fourier transform.

        A multiple sequence alignment program, MAFFT, has been developed. The CPU time is drastically reduced as compared with existing methods. MAFFT includes two novel techniques. (i) Homo logous regions are rapidly identified by the fast Fourier transform (FFT), in which an amino acid sequence is converted to a sequence composed of volume and polarity values of each amino acid residue. (ii) We propose a simplified scoring system that performs well for reducing CPU time and increasing the accuracy of alignments even for sequences having large insertions or extensions as well as distantly related sequences of similar length. Two different heuristics, the progressive method (FFT-NS-2) and the iterative refinement method (FFT-NS-i), are implemented in MAFFT. The performances of FFT-NS-2 and FFT-NS-i were compared with other methods by computer simulations and benchmark tests; the CPU time of FFT-NS-2 is drastically reduced as compared with CLUSTALW with comparable accuracy. FFT-NS-i is over 100 times faster than T-COFFEE, when the number of input sequences exceeds 60, without sacrificing the accuracy.
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          RAxML-III: a fast program for maximum likelihood-based inference of large phylogenetic trees.

          The computation of large phylogenetic trees with statistical models such as maximum likelihood or bayesian inference is computationally extremely intensive. It has repeatedly been demonstrated that these models are able to recover the true tree or a tree which is topologically closer to the true tree more frequently than less elaborate methods such as parsimony or neighbor joining. Due to the combinatorial and computational complexity the size of trees which can be computed on a Biologist's PC workstation within reasonable time is limited to trees containing approximately 100 taxa. In this paper we present the latest release of our program RAxML-III for rapid maximum likelihood-based inference of large evolutionary trees which allows for computation of 1.000-taxon trees in less than 24 hours on a single PC processor. We compare RAxML-III to the currently fastest implementations for maximum likelihood and bayesian inference: PHYML and MrBayes. Whereas RAxML-III performs worse than PHYML and MrBayes on synthetic data it clearly outperforms both programs on all real data alignments used in terms of speed and final likelihood values. Availability RAxML-III including all alignments and final trees mentioned in this paper is freely available as open source code at http://wwwbode.cs.tum/~stamatak stamatak@cs.tum.edu.
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            Author and article information

            Affiliations
            [a ]Institute of Tropical Medicine Laboratory of Virology LIM52
            [b ]Department of Infectious Diseases, Clinics Hospital of the School of Medicine
            [c ]Institute of Tropical Medicine Laboratory of Seroepidemiology, University of São Paulo, São Paulo, Brazil
            [d ]Institute of Virology, University of Bonn Medical Centre, Bonn, German Centre for Infection Research (DZIF), partner site Bonn-Cologne, Germany
            [e ]Pathology Department of the School of Dentistry, University of São Paulo, São Paulo, Brazil.
            Author notes
            []Correspondence: Tania Regina Tozetto-Mendoza, Rua Dr. Enéias de Carvalho Aguiar, 470. Cerqueira Cesar, São Paulo-S.P, Brazil (e-mail: tozetto@ 123456usp.br ).
            Journal
            Medicine (Baltimore)
            Medicine (Baltimore)
            MEDI
            Medicine
            Wolters Kluwer Health
            0025-7974
            1536-5964
            December 2016
            02 December 2016
            : 95
            : 48
            27902590
            5134807
            MD-D-16-05016
            10.1097/MD.0000000000005291
            05291
            (Editor)
            Copyright © 2016 the Author(s). Published by Wolters Kluwer Health, Inc. All rights reserved.

            This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0

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            4850
            Research Article
            Observational Study
            Custom metadata
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            aids-ks, genotype, hhv-8, orf k1, saliva

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