Стилистический эффект разговорной речи и его составляющие

В обучении русскому языку как иностранному на современном этапе большое внимание уделяется особенностям русской разговорной речи. Это обусловлено целым рядом причин, среди которых, на наш взгляд, можно выделить следующие: во-первых, разговорная речь всегда отличается активностью проникновения во все сферы жизнедеятельности людей и функционирует как в повседневном общении, так и в различных сферах (литературе, кино, политике и т.д.). Во-вторых, разговорная речь носит многожанровый характер, что зачастую затрудняет ее понимание иностранными студентами. В-третьих, в разговорную речь помимо слов нейтрального стиля все активнее стала проникать арготическая лексика. Именно в связи с этим особый интерес у нас вызывает разговорный стиль речи в преломлении на инофонную аудиторию

Influence of HAART on Alternative Reading Frame Immune Responses over the Course of HIV-1 Infection

Background: Translational errors can result in bypassing of the main viral protein reading frames and the production of alternate reading frame (ARF) or cryptic peptides. Within HIV, there are many such ARFs in both sense and the antisense directions of transcription. These ARFs have the potential to generate immunogenic peptides called cryptic epitopes (CE). Both antiretroviral drug therapy and the immune system exert a mutational pressure on HIV-1. Immune pressure exerted by ARF CD8(+) T cells on the virus has already been observed in vitro. HAART has also been described to select HIV-1 variants for drug escape mutations. Since the mutational pressure exerted on one location of the HIV-1 genome can potentially affect the 3 reading frames, we hypothesized that ARF responses would be affected by this drug pressure in vivo. Methodology/Principal findings: In this study we identified new ARFs derived from sense and antisense transcription of HIV-1. Many of these ARFs are detectable in circulating viral proteins. They are predominantly found in the HIV-1 env nucleotide region. We measured T cell responses to 199 HIV-1 CE encoded within 13 sense and 34 antisense HIV-1 ARFs. We were able to observe that these ARF responses are more frequent and of greater magnitude in chronically infected individuals compared to acutely infected patients, and in patients on HAART, the breadth of ARF responses increased. Conclusions/Significance: These results have implications for vaccine design and unveil the existence of potential new epitopes that could be included as vaccine targets.International AIDS Vaccine Initiative (IAVI

Cellular immune response against HIV-1 cryptic peptides

INTRODUÇÃO E OBJETIVOS: Uma fonte secundária e não convencional de peptídeos que se ligam as moléculas MHC de classe I tem sido descrita como responsável por produzir peptídeos crípticos. Esses peptídeos são imunogênicos e portanto, capazes de induzir uma resposta imunológica por células T e assim, contribuir com a resposta total exercida pelas células T CD8+, colaborando na pressão que leva HIV-1 ao processo de mutação, e consequentemente ao escape viral. Alguns pacientes, que correspondem a menos de 5% da população infectada, são capazes de naturalmente controlar a progressão da doença, mantendo a contagem de célula T CD4+ acima de 500 células/uL ou mantendo a carga viral abaixo de 2.000 cópias/mL, por ao menos 12 meses, sem ser submetido a tratamento com antirretrovirais ou esquema HAART. Avaliar a resposta imunológica destes pacientes, controladores da infecção, contra peptídeos crípticos pode nos fornecer informações importantes que colaborem com o desenvolvimento de novas estratégias preventivas. METODOLOGIA: A resposta imunológica contra peptídeos crípticos, estes derivados da transcrição da seqüência consenso e da seqüência inversa do gene do HIV-1, foram avaliados em vários conjuntos (pools), utilizando amostras coletadas de pacientes controladores, tanto avirêmicos, também conhecidos como controladores de elite (carga viral < limite de detecção), bem como virêmicos (carga viral < 2.000 cópias/mL) e, de pacientes progressores. Foi observada que a resposta imunológica contra peptídeos crípticos é mais freqüente, com maior amplitude e magnitude entre os pacientes controladores comparados ao que foi observado entre pacientes progressores. Esta resposta, entretanto, parece inverter ao longo da infecção, como observada utilizando as amostras coletadas em momento tardio da infecção, onde os controladores parecem perder sua capacidade de responder aos peptídeos crípticos, enquanto que os progressores desenvolveram resposta, ressaltando que os pools indutores de resposta nas duas fases foram diferentes. Sugerindo que a resposta imunológica contra peptídeos crípticos pode exercer papel importante de pressão sobre o vírus, levando-o ao processo de escape viral. CONCLUSÔES E IMPORTÂNCIA: Peptídeos crípticos são capazes de induzir resposta imunológica e colaborar para explicar como ocorre a seleção de alguns vírus, seja este devido à mudança na expressão das proteínas principais do HIV-1, seja diretamente gerando vírus defeituoso e não infectante. Os peptídeos crípticos podem ser incluídos em desenhos de vacina, com o intuito de aumentar a amplitude e a magnitude da resposta imunológica por células T e consequentemente, aumentar a proteção contra infecção ou progressão da infecção pelo HIV-1BACKGROUND: A second and unconventional source of peptides that bind to MHC class I molecule has been described to produce cryptic peptides, which are immunogenic and are able elicit T cell response, that contributes to total CD8+ T cell immune response and then exert mutation pressure on HIV-1, leading to virus escape. Some rare patients, less than 5% of infected population, are naturally able to control disease progression, either maintaining CD4+ T cells over 500 cells/uL or viral load under 2,000 copies/mL, without being treated with HAART, for at least 12 months. Understanding their immune response to cryptic peptides might be a great value to help on developing better prevention strategies. METHODOLOGY: Immune response to cryptic peptides, derived from sense and antisense transcription of HIV-1, was evaluated in pools using samples from Elite (aviremic) or HIV (viremic, < 2,000 copies/mL) controllers and progressors. Immune response to cryptic peptides are more frequent, with a larger breadth and of greater magnitude in controllers than in progressors, and this response is inversed seen in a later time point, when controllers seems to lose this response, while progressors developed it, showing cryptic peptides immune response to different pools, suggesting that immune response to cryptic peptides might play some role in pressuring the virus mutation escape. CONCLUSIONS AND SIGNIFICANCE: cryptic peptides can elicit immune response and help to explain how some virus selection happens, either by changing expression of crucial HIV-1 proteins or generating defective virus. They can be included in vaccine design for enhancing the magnitude and breadth of T cell immune response and consequently the protection against infection or progression of HIV-1 infectio

Alternate reading frame-encoded amino acids in circulating viral sequences.

<p>A) Distribution of known mutant origins across viral ARF sequences attributable to a particular cause based on information associated with the sequence accession the NCBI nr protein database presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0039311#pone.0039311.s002" target="_blank">Table S2</a>. B) Composition of viral coding sequence computed as a percentage assigned to the coding sequence for the Env, Gag, Pol poly-proteins based on nucleotide base counts for a particular gene region compared to the total nucleotide count for the structural genes of the virus. Gag comprises 1,503 nt of the total of 6,878 nt of structural gene sequence; Pol comprises 3,139 nt of the total; Env comprises of 2,571 nt of the total. This is the distribution of origins within the genome that would be expected if originating events for the incorporation of ARF and their detection in circulating HIV-1 viral sequences were distributed randomly throughout the genome. C) The distribution of ARF incorporated into circulating viral sequences that was observed in our searches of NCBI nr protein database for ARF sequences in circulating HIV-1 viral sequences. The percentages were computed by dividing the number of BLAST hits with ARF sequence incorporated into a given gene region by the 123 total hits examined. D) A three-way alignment between the HXB-2 reference sequence for the Env region, the accession AAL78125.1 and the alternate reading frame encoded ORF 67. E) A three-way alignment between the HXB-2 reference sequence for the Gag region, the accession AEQ21252.1 and the alternate reading frame encoded ORF 3. F) A three-way alignment between the HXB-2 reference sequence for the Pol region, the accession CAF29000.1 and the alternate reading frame encoded ORF 23. All three-way alignments were generated by combining two pair-wise alignments created in Geneious, followed by manual editing. Note each accession is similar to both the HXB-2 reference sequence for the structural proteins and the alternate reading frame encoded sequence, but not to both sequences simultaneously within the same region of the sequence.</p

ARF responses in one HIV-1 chronically infected patients before and on HAART.

<p>In the pie charts each color represents a pool of immune response that the patient mounted against. Numbers inside the pie charts correspond to the magnitude of the response against the pool in SFU/million PBMC.</p

Breadth of ARF responses in chronically infected patients.

<p>A) Number of detectable responses observed for each individual ARF peptide-pool tested. B) Number of ARF peptide pools that induced detectable responses in each chronically infected individual. Grey bars represent patients Before HAART and black bars represent patients On HAART. Patients #47 and #48 were only tested before HAART introduction and patient #49 was only tested after HAART.</p

Patients’ characteristics.

<p>Table depicts whether patients were HIV-1 acutely or chronically infected, stage of treatment, the number of patients used in the study, the number of extra patients included in the study, total number of samples tested, mean frequency of CD4⁺ and CD8⁺ T cells (cells/µL) and viral load (copies/mL).</p

HIV-1 genome (HXB-2 strain), and localization of the 47 alternative reading frames (ARF).

<p>Figure depicts all 199 ARF-tested peptides. These include 13 forward ARF within frames 1, 2 or 3 (in green) and 34 reverse ARF within frames -1, -2 or -3 (in purple). HIV-1 classically defined encoding genes are shown in blue.</p

Breadth of ARF responses in acutely infected patients.

<p>A) Number of detectable responses observed for each individual ARF peptide-pool tested. B) Number of ARF peptide pools that induced detectable responses in each acutely infected individual. Blue bars represent patients On HAART and red bars represent patients Off HAART. We were unable to follow patients #26, #27 and #28 before HAART interruption.</p