On Hepatitis C Virus Evolution: The Interaction between Virus and Host towards Treatment Outcome

Background:Hepatitis C is a disease spread throughout the world. Hepatitis C virus (HCV), the etiological agent of this disease, is a single-stranded positive RNA virus. Its genome encodes a single precursor protein that yields ten proteins after processing. NS5A, one of the non-structural viral proteins, is most associated with interferon-based therapy response, the approved treatment for hepatitis C in Brazil. HCV has a high mutation rate and therefore high variability, which may be important for evading the immune system and response to therapy. The aim of this study was to analyze the evolution of NS5A quasispecies before, during, and after treatment in patients infected with HCV genotype 3a who presented different therapy responses.Methods:Viral RNA was extracted, cDNA was synthesized, the NS5A region was amplified and cloned, and 15 clones from each time-point were sequenced. The sequences were analyzed for evolutionary history, genetic diversity and selection.Results:This analysis shows that the viral population that persists after treatment for most non-responder patients is present in before-treatment samples, suggesting it is adapted to evade treatment. In contrast, the population found in before treatment samples from most end-of-treatment responder patients either are selected out or appears in low frequency after relapse, therefore changing the population structure. The exceptions illustrate the uniqueness of the evolutionary process, and therefore the treatment resistance process, in each patient.Conclusion:Although evolutionary behavior throughout treatment showed that each patient presented different population dynamics unrelated to therapy outcome, it seems that the viral population from non-responders that resists the treatment already had strains that could evade therapy before it started. © 2013 Bittar et al.

Verificação da formação de complexos protéicos nos telômeros de L. amazonensis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Caracterização estrutural e das interações entre a Proteína G do hRSV e potenciais inibidores

Pós-graduação em Microbiologia - IBILCE

Evolução das quasiespécies da proteína NS5A do vírus da hepatite C genótipo 3a

Pós-graduação em Genética - IBILCE

Caracterização parcial e desenvolvimento de oligonucleotídeos específicos para detecção de sequivírus infectando alface

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Estudo das interações entre a proteína TRF de Leishmania amazonensis (LaTRF) e suas possíveis parcerias

Pós-graduação em Ciências Biológicas (Genética) - IBB

Epidemiologia molecular das estirpes LaSota e São João do Meriti do vírus da Doença de Newcastle

Pós-graduação em Microbiologia Agropecuária - FCAV

Telomere and Telomerase Biology

Telomeres are the physical ends of eukaryotic linear chromosomes. Telomeres form special structures that cap chromosome ends to prevent degradation by nucleolytic attack and to distinguish chromosome termini from DNA double-strand breaks. With few exceptions, telomeres are composed primarily of repetitive DNA associated with proteins that interact specifically with double- or single-stranded telomeric DNA or with each other, forming highly ordered and dynamic complexes involved in telomere maintenance and length regulation. In proliferative cells and unicellular organisms, telomeric DNA is replicated by the actions of telomerase, a specialized reverse transcriptase. In the absence of telomerase, some cells employ a recombination-based DNA replication pathway known as alternative lengthening of telomeres. However, mammalian somatic cells that naturally lack telomerase activity show telomere shortening with increasing age leading to cell cycle arrest and senescence. In another way, mutations or deletions of telomerase components can lead to inherited genetic disorders, and the depletion of telomeric proteins can elicit the action of distinct kinases-dependent DNA damage response, culminating in chromosomal abnormalities that are incompatible with life. In addition to the intricate network formed by the interrelationships among telomeric proteins, long noncoding RNAs that arise from subtelomeric regions, named telomeric repeat-containing RNA, are also implicated in telomerase regulation and telomere maintenance. The goal for the next years is to increase our knowledge about the mechanisms that regulate telomere homeostasis and the means by which their absence or defect can elicit telomere dysfunction, which generally results in gross genomic instability and genetic diseases.

RPA-1 from Leishmania amazonensis (LaRPA-1) structurally differs from other eukaryote RPA-1 and interacts with telomeric DNA via its N-terminal OB-fold domain

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Molecular and phylogenetic characterization based on the complete genome of a virulent pathotype of Newcastle disease virus isolated in the 1970s in Brazil

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Obtenção de uma nova proteína recombinante componente do complexo telemérico LAGT1 de Leishmania Amazonensis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Glyceraldehyde 3-phosphate dehydrogenase-telomere association correlates with redox status in trypanosoma cruzi

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The putative Leishmania telomerase RNA (leishTER) undergoes trans-splicing and contains a conserved template sequence

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Análise do efeito in vitro de acridonas na replicação do Vírus da Hepatite C

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Temperature dependence of conformational properties of short polyelectrolytes from simulations at a single temperature

We use a series expansion method introduced recently by Rickman and Phillpot (Phys. Rev. Lett. 1991, 66, 349) to study the temperature dependent conformational properties of short ionized polyelectrolyte chains in ionic solutions by conducting simulations at a single temperature. The charged beads located at the sites of a cubic lattice interact through screened Coulombic interactions. It is shown that this method provides results that correlate with other Monte Carlo simulations, performed over a range of temperatures, where conformational transitions induced by thermal and screening effects occur. It is also shown that the method can be used successfully when the potential is weakly dependent on temperature. © 1994 American Chemical Society.