文33块沙二下段油藏动态模型及剩余油预测

By applying synthetically multi-subject theories, methods and technology, such as petroleum geology, sedimentology, seep mechanics, geochemistry, geophysics and so on; and by making full use of computer; combining quantity and quality, macroscopic and microscopic, intensive static and active description, comprehensive studying and physical modeling, 3 dimension and 4 dimension description; the paper took Wen-33 block of Zhongyuan oil field as an example; and studied reservoir macroscopic and microscopic parameter changing rule and evolve mechanics in different water-blood stage. The reservoir dynamic model and remaining-oil distribution mode was established, and several results were achieved as follows: (1) Three types of parameter gaining, optimizing and whole data body of Wen33th reservoir were established. Strata framework, structure framework, reservoir types and distribution of Wen33th reservoir were discussed. Reservoir genesis types, space distribution law and evolve rule of Wen33th reservoir were explained. 4D dynamic model of macroscopic parameter of reservoir flow dynamic geologic function of Wen33th reservoir was established. The macroscopic remaining-oil distribution and control factor was revealed. The models of the microscopic matrix field, pore-throat network field, fluid field, clay mineral field of Wen-33 block were established. The characters, changing rules and controlled factors in different water stage were revealed. The evolve rule and mechanics of petroleum fluid field in Wen-33 block reservoir were revealed. Macroscopic and microscopic remaining oil distribution mode of Wen-33 block were established. Seven types, namely 12 shapes of dynamic model of microscopic remaining oil were discussed, and the distribution of mover remaining oil was predicted. Emulation model: mathematical model and prediction model of Wen-33 block were established. The changing mechanics of reservoir parameter and distribution of remaining-oil were predicted. Firstly, the paper putting forward that the dynamic geologic function of petroleum development is the factor of controlling remaining-oil, which is the main factor leading to matrix field, network field, clay mineral field, fluid field, physic and chemical field, stress field and fluid field forming and evolving. (10) A set of theories, methods and technologies of investigating, describing, characterizing and predicting complex fault-block petroleum were developed.

济阳坳陷及其南缘奥陶系碳酸盐岩潜山储集性及控制因素

The main research area of this thesis is Jiyang Depression in the Bohaiwan Basin and its southern margin. The object formation is Ordovician carbonate. The research is based on the outcrop observation and measurement of Ordovician carbonate and the drilling data of the oilfield. The internal reservoir characteristics of carbonate buried hill and its distribution were studied by comprehensive methods of sedimentology, reservoir geology and structural geology and technics of cathodoluminescence(CL)3electron microprobe,casting and C O isotope analysis etc. The influence depth of paleokarst facies formed during the Paleozoic is discriminated as 36-84m. The sollution porosity is well developed in paleokarst facies of Ordovician carbonate and is an important type of internal reservoir of buried hill. It may be infered that the fractures may be formed mainly during the Mesozoic and Cenozoic, they were not developed during the early Paleozoic when only micro-fractures might be created. The carbon and oxigen isotope analysis shows that the calcite cements in the fractures of Ordovician carbonate and secondary solution pores were related with meteoric water and three stages of fractures were divided. The reservoir space of Ordovician carbonate are mainly secondary porosity, cavern and fracture. The development of structural fracture was controlled by the lithology and tectonic background. More fractures exist in dolomite than that in limestone. There are also more fractures near the fault and the axis of fold. The development of porous reservoir is mainly controlled by the lithology and diagenesis, especially dolomitization and dissolution. It also results in the heterogeneity vertically. So the lithology is the basic factor for the forming of internal reservoir of buried hill and the tectogenesis and diagenesis are key factors to improve it. The porosity in carbonate might experienced solution-cementation-resolution or recementation. The porosity evolution history was a kind of historical dynamic equilibrium. The internal reservoir of Ordovician carbonate is the comprehensive result of constructive and/or destructive diagenesis. The worm's eye maps of the early Paleozoic and middle-upper Proterozoic were plotted. It was inferred that the paleostress field evoluted from NNW to NW during the Mesozoic and Cenozoic. Three types of buried hills can be divided: C-P/Pzi, Mz/ Pzi and E/ Pzi. The unconformity of the buried hill of E/ Pzi type, comparatively, was formed and reconstructed latestly, t he p orous r eservoir c ould b e w ell p reseved. T his c ondition w as v ery favorable t o t he migration and accumulation of oil and gas and could form upstanding association of source-reservoir-cap rocks. The buried hills of Mz/ Pzi and C-P/Pz] type were took second place.

利用分频与反演提高地震资料信噪比与分辨率方法研究

This thesis mainly talks about the wavelet transfrom and the frequency division method. It describes the frequency division processing on prestack or post-stack seismic data and application of inversion noise attenuation, frequency division residual static correction and high resolution data in reservoir inversion. This thesis not only describes the frequency division and inversion in theory, but also proves it by model calculation. All the methods are integrated together. The actual data processing demonstrates the applying results. This thesis analyzes the differences and limitation between t-x prediction filter and f-x prediction filter noise attenuation from wavelet transform theory. It considers that we can do the frequency division attenuation process of noise and signal by wavelet frequency division theory according to the differences of noise and signal in phase, amplitude and frequency. By comparison with the f-x coherence noise, removal method, it approves the effects and practicability of frequency division in coherence and random noise isolation. In order to solve the side effects in non-noise area, we: take the area constraint method and only apply the frequency division processing in the noise area. So it can solve the problem of low frequency loss in non-noise area. The residual moveout differences in seismic data processing have a great effect on stack image and resolutions. Different frequency components have different residual moveout differences. The frequency division residual static correction realizes the frequency division and the calculation of residual correction magnitude. It also solves the problems of different residual correction magnitude in different frequency and protects the high frequency information in data. By actual data processing, we can get good results in phase residual moveout differences elimination of pre-stack data, stack image quality and improvement of data resolution. This thesis analyses the characters of the random noises and its descriptions in time domain and frequency domain. Furthermore it gives the inversion prediction solution methods and realizes the frequency division inversion attenuation of the random noise. By the analysis of results of the actual data processing, we show that the noise removed by inversion has its own advantages. By analyzing parameter's about resolution and technology of high resolution data processing, this thesis describes the relations between frequency domain and resolution, parameters about resolution and methods to increase resolution. It also gives the processing flows of the high resolution data; the effect and influence of reservoir inversion caused by high resolution data. Finally it proves the accuracy and precision of the reservoir inversion results. The research results of this thesis reveal that frequency division noise attenuation, frequency residual correction and inversion noise attenuation are effective methods to increase the SNR and resolution of seismic data.

油气藏自然电位异常与油气赋存的相关性研究

The Stack Spontaneous Potential (SSP) is a direct hydrocarbon location technology and a new hydrocarbon detection method with independent intellectual property. A subsurface hydrocarbon accumulation associated with the upward hydrocarbon micro seepage induces a relatively strong negative potential abnormal zone, of which the anomaly can be measured on the surface with specially designed instruments through careful field measuring procedures. With special software programmed according to a unique geochemical and geophysical model, the original data are analyzed, processed and interpreted on the computer, and then on a series of resulting anomaly distribution maps and/or profiles, the favorable surface locations of the hydrocarbon accumulations can be easily identified. The study of the SSP has been started since 1989, and especially from 1996 to 1997, both profile and area tests were conducted in the Daqing Oilfield. On the testing line of 15kms, there are 6 wells in total, among which some are oil-producing wells, and some are water-producing wells. The final matching ratio of the favorable oil well locations and the possible water well locations predicted by the SSP to those of known wells was up to 83 percent. In the area test, of which the acreage is 800 km2, the matching ratio compared with the existing wells was 87 percent; furthermore, regarding to wells subsequently drilled after the test, the matching ratio was 85 percent. The matching ratio in the development area is more about 10 percent than those of in exploration area. The reason is that, comparing the exploration area, the development area acreage is less and the container rocks are more simplex. In development area there is not so much interference of SSP also. Since 1997 the SSP has been tested and applied all over China to a number of hydrocarbon bearing basins and known oil fields, including the Daqing, Jiangsu, Changqing, Shengli, Nanyang, Jianghan and Zhongyuan Oilfields, only to name a few. The SSP surveys in total areas of over 10,000km2 in more than 30 regions in China so far have been completed in various exploration and development stages, the satisfactory outcomes of which have further evidenced that the dependence between the SP anomaly and abundance of hydrocarbon. Up to date, a substantial amount of successful tests and actual surveys finished in exploration and development practices have evidenced that the SSP is significantly more reliable in comparison with any other similar direct hydrocarbon indication technique generally known to the oil industry, such as the Redox. The SSP can be applied to search for almost all kinds of hydrocarbon accumulations, regardless of the type of traps, such as structural, stratigraphic, buried hill traps, and so on; however, it is interesting to be noted that the SSP seems to be particularly effective in detecting the stratigraphic oil traps according to our practices. On the other hand, there is virtually no surface geographical constrains in terms of field data acquisition, except for those water covered areas, because of the inherent characteristics of the technology itself. Furthermore, utilizing the SSP requires no special considerations to subsurface geological conditions in regard to formation resistivity, since the SSP measurements will not be influenced by either overly high or overly low resistivity of formations lying above the hydrocarbon accumulations. There are two kind of theory, of which, as we know one is called hypbyssal theory such as "Redox"[61 the other is call plutonic theory such as cracking of hydrocarbon [8][9] and natural polarization [3], to describe the mechanism of SP anomaly of oil reservoir and to indicate that the dependence between the SP abnormality and abundance of hydrocarbon has be existed theoretically/The quantitative dependence, which has not been founded due to the complicity of container rocks, be discovered during the exploration and development practices is the crux to the quantitative analysis of SP Anomaly processing. Based on the thorough study of the complex of collector rocks, every kind of thickness of collector rock can be conversed to be a standard effective thickness; the thickness is called apparent effective thickness (AET). The conversation coefficient (ai, 1=1,2,3) could be determined by the variety of every collector rock storability (CRS). The discoveration of quantitative: dependence between AET and the amplitude of SSP, in the practices of exploration and development, is a promotion for the SSP supplied in the oil exploration, and make the data analysis forward to the quantitative stage.

黄骅坳陷高尘头地区储层非均质性及成藏研究

Gaochentou region is located in the southwest direction of Gaochentou village in Huanghua city of Hebei province. In regionally structural position, It lies in Qikou sag In the middle part of Huanghua depression, which belongs to the east part of the south Dagang structure zone in the middle part of Huanghua depression. Its' very beneficial at regional structure in Gaochentou , and It becomes the advantage area for oil and gas gathered and preserved, Sandstone reservoir of Dongying Formation is main bearing bed .Dongying Formation in Gaochentou region of Huanghua depression is consisted of set of mudstone and sandstone interbeds by deposited delta fades . Dongying Formation can be divided into 3 members from above to below: the first member of Dongying Formation (FMDF), the second member of Dongying Formation (SMDF), and third member of Dongying Formation (TMDF). The lithology of the upper part of FMDF was consisted of mostly middle-grained and fine-grained sandstone, and it is small for the oil-bearing area of the sand bodies .The lithology of the lower part is coarse-grained sandstone bodies which are well connected between sandstone bodies of wells, and the lower part was main bed of oil production in Dongying Formation; SMDF and TMDF are consisted of larger scale set of mudstone, in which the sandbodies are lenticular and pinch out quickly, and the lithology was mostly fine sandstone and silt stone, in which there are little oil and gas .Because the reservoirs in this area are largely influenced by the factors such as lithology, fault and others, and the reservoirs have the strong,heterogeneity , there exists the problem of oil-down and water-up for vertical distribution of oil and gas bearing. It is not very clearly for the three dimension distribution of sandstone , and the geology researchs is not enough. So, it can't satisfy the need of further development and production for Gaochentou oilfield.Having the key problem of oil-down and water-up and the mechanism of the reservoir for Gaochentou area, There are as follow study works, the first, is study of the high-resolution correlation of sequence stratigraphy and sedimentary microfacies. Dongying Formation was divided into three parasequence sets and each parasequence set was divided into different amount of parasequences. FMDF, as the main oil and gas producing bed, can be divided into seven parasequences. Oil and gas are discovered in six parasequences except the seventh. On the basis of study of sedimentary microfacies, the sediments of Dongying Formation are considered deposited mainly in delta front subfacies. The microfacies types of Dongying Formation are sub-water distirbutary channel, sub-water natural bank, inter distributary channel bay, distributary channel mouth dam, and delta front mat sand.Seismic facies analysis and logging-constrained inversion technique were applied by Author for transverse prediction of sandstone reservoir. Having 4 modes of interwell single sandbodies correlation technique, Author have described distribution characteristics of sandbodies, and established geological reservoir model of Gaochentou reservoir.Author presented that the reservoirs characteristic have very strong heterogeneity ,and In the section of sandstone interlayed with mudstone,the folium sandstone interlayed with each other, and the wedge shaped sandbodies pinched out in the mudstone. So the pinch-out up sandstone trap and lenticular sandstone trap are easily formed. They are most small scale overlying pinches out in the place of slope. This article applies the concept of deep basin oil to resolve reasonably the problem of which the oil is below the water in Gaochentou area. Combined with the study of sedimentary facies, reservoir and other aspects, the mechanism and patterns of deep basin oil are studied on the basis of characteristics in Gaochentou area.On the basis of the above study, the mechanism of the oil and gas' migration and accumulation in isotropic sandstone and heterogeneous sandstone are thoroughly analyzed through experiments on physical modeling. Experiments on physical modeling show that the discrepancy between sand layers with different permeability and thickness has important influence on the direction, path, and injection layer of oil's migration. At the beginning of the injection of oil and gas in high permeability sand layer, the pressure is low, the migration resistance is small, and the oil and gas are more easily displacing the water in sand. So it can act as good transformation layer or reservoir. But at the beginning of the injection of oil and gas in sand layer with low permeability, the pressure is high, the migration resistance is big, and the oil and gas are more difficultly displacing the water in sand. So it can only act as bad or worse transformation layer or reservoir. Even if it cannot act as transformation layer or reservoir, it can act as water layer or dry layer. The discrepancy between sand layers on permeability and thickness can make discrepancy in injection of oil and gas between different layers. Consequently it leads to small amount of oil and gas injection in sand layers with low permeability. Ultimately it affects the oil's accumulation and distribution in different sand layers.At Last, combining analysis of the structure and pool forming condition, The thesis has established models of reservoir formation to predict the advantage distribution of oil and gas bearing , and put forward the prospective target It is not only of theoretical signification for explosion and importance, but also has realistic value in guiding the progressive petroleum exploration and exploitation.

An industrial scale dehydration process for natural gas involving membranes

An industrial scale dehydration process based on hollow fiber membranes for lowering the dew point of natural gas is described in this paper. A pilot test with the feed flux scale of 12x10(4) Nm(3)/d was carried out. Dew points of -8 degreesC-13 degreesC at a gas transport pressure in the pipeline of 4.6M Pa and methane recovery of more than 98% were attained. The water vapor content of the product gas could be maintained around 0.01 vol% during a continuous run of about 700 hours. The effects of feed flux and operation pressure on methane recovery and water vapor content were also investigated. Additionally, some auxiliary technologies, such as a full-time engine using natural gas as fuel and the utilization of vent gas in the process, are also discussed. A small amount of the vent gas from the system was used as a fuel for an engine to drive vacuum pumps, and the heat expelled from the engine was used to warm up the natural gas feed. The whole system can be operated in a self-sustainable manner from an energy point of view, and has a relatively high efficiency in the utilization of natural gas.

A species invasion mediated through habitat structure, intraguild predation and parasitism.

With field, laboratory, and modeling approaches, we examined the interplay among habitat structure, intraguild predation (IGP), and parasitism in an ongoing species invasion. Native Gammarus duebeni celticus (Crustacea: Amphipoda) are often, but not always, replaced by the invader Gammarus pulex through differential IGP. The muscle-wasting microsporidian parasite Pleistophora mulleri infects the native but not the invader. We found a highly variable prevalence of P. mulleri in uninvaded rivers, with 0–91% of hosts parasitized per sample. In addition, unparasitized natives dominated fast-flowing riffle patches of river, whereas parasitized individuals dominated slower- flowing, pooled patches. We examined the survivorship of invader and native in single and mixed-species microcosms with high, intermediate, and zero parasite prevalence. G. pulex survivorship was high in all treatments, whereas G. duebeni subsp. celticus survivorship was significantly lower in the presence of the invader. Further, parasitized G. duebeni subsp. celticus experienced near-total elimination. Models of the species replacement process implied that parasite-enhanced IGP would make invasion by G. pulex more likely, regardless of habitat and parasite spatial structure. However, where heterogeneity in parasite prevalence creates a landscape of patches with different susceptibilities to invasion, G. pulex may succeed in cases where invasion would not be possible if patches were equivalent. The different responses of parasitized and unparasitized G. duebeni subsp. celticus to environmental heterogeneity potentially link landscape patterns to the success or failure of the invasion process.

Quantum homogenization for continuous variables: Realization with linear optical elements

Recently Ziman et al. [Phys. Rev. A 65, 042105 (2002)] have introduced a concept of a universal quantum homogenizer which is a quantum machine that takes as input a given (system) qubit initially in an arbitrary state rho and a set of N reservoir qubits initially prepared in the state xi. The homogenizer realizes, in the limit sense, the transformation such that at the output each qubit is in an arbitrarily small neighborhood of the state xi irrespective of the initial states of the system and the reservoir qubits. In this paper we generalize the concept of quantum homogenization for qudits, that is, for d-dimensional quantum systems. We prove that the partial-swap operation induces a contractive map with the fixed point which is the original state of the reservoir. We propose an optical realization of the quantum homogenization for Gaussian states. We prove that an incoming state of a photon field is homogenized in an array of beam splitters. Using Simon's criterion, we study entanglement between outgoing beams from beam splitters. We derive an inseparability condition for a pair of output beams as a function of the degree of squeezing in input beams.

An isothermal-isobaric Langevin thermostat for simulating nanoparticles under pressure: Application to Au clusters

We present a method for simulating clusters or, molecules subjected to an external pressure, which is exerted by a pressure-transmitting medium. It is based on the canoninical Langevin thermostat, but extended in such a way that the Brownian forces are allowed to operate only from the region exterior to the cluster. We show that the frictional force of the Langevin thermostat is linked to the pressure of the reservoir in a unique way, and that this property manifests itself when the particle it acts upon is not pointlike but has finite dimensions. By choosing appropriately the strength of the random forces and the friction coefficient, both temperature and pressure can be controlled independently. We illustrate the capabilities of this new method by calculating the compressibility of small gold clusters under pressure.

Toxicidade de químicos em mistura: o caso da albufeira do Alqueva

In the environment humans and biota are generally exposed to chemical mixtures rather than individual chemicals. Therefore, when assessing the environmental risk of chemicals, it is important to consider chemical mixtures and their possible interactions. The main objective of this work focused on the environmental risk assessment of pesticides found in the water of the Alqueva reservoir and their binary combinations. In this aquatic ecosystem several pesticides were above of the environmental quality standards. But in addition, there were several sampling points of the reservoir where ecotoxicity was observed despite the presence of these contaminants at low concentrations. Here, a component-based approach was used to assess the effects of the pesticide mixtures. The effects of the binary combinations of four herbicides, atrazine (ATR), terbuthylazine (TER), simazine (SIM) and metolachlor (MET), on the growth rate of the microalgae Pseudokirchneriella subcapitata and the effects of the binary combinations of the s-triazine herbicides ATR and TER and the insecticide chlorpyrifos (CPF) on the swimming behaviour and acetylcholinesterase (AChE) activity of the zebrafish Danio rerio were assessed using the two reference models of concentration addition (CA) and independent action (IA). Moreover, the combined effects of the herbicides (ATR, TER and MET) and the insecticide CPF were also tested on the swimming behaviour and AChE activity of the aquatic midge Chironomus riparius after the cholinesterases characterization. In this risk characterization, the calculated risk quotients for the herbicides ATR, TER, SIM and MET were higher than 1, meaning that these herbicides present a high risk for the Alqueva ecosystem. As expected, the microalgae P. subcapitata was the most sensitive species to the herbicides. However, despite these herbicides pose no or low risk to other aquatic organisms tested in this study, with EC50 values much higher than the concentrations found in this aquatic ecosystem, they are able to increase the toxic effects of CPF when they are tested in binary mixtures. Moreover, the risk quotients of mixtures of these herbicides present simultaneously in three different locations of the reservoir were also higher than 1, so this confirms the fact that these herbicides when present in mixtures, present a greater risk for this ecosystem than the expected considering each single chemical by its own.

Propriedades de lamas de salinas de Aveiro, tendo em vista aplicações dermoterapêuticas e dermocosméticas

Desde tempos históricos que diferentes tipos de lama são utilizados para aplicações externas no corpo humano, para fins terapêuticos e cosméticos. As lamas cuja beneficiação e caracterização físico-química são apresentadas nesta dissertação são formadas no ambiente hipersalino que existe nas salinas da Troncalhada e de São Tiago da Fonte, localizadas no estuário do rio Vouga, em Aveiro, Portugal. As salinas são constituídas por uma sequência de tanques onde, no período de verão, da água do mar e por evaporação natural, se produz sal marinho que precipita no último tanque (o cristalizador) do qual é extraído. Na base dos tanques ocorrem lamas que correspondem a sedimentos constituídos por material argiloso de cor preto-cinzento e que incorporam argila, silte, areia, bioclastos, sal, matéria orgânica e gás. A componente inorgânica da lama extraída do cristalizador foi estudada por Difracção de Raios-X (DRX) e Fluorescência de Raios-X (FRX), enquanto a componente orgânica da mesma lama foi estudada por Cromatografia de Gás- Espectrometria de Massa (GC-MS). Os estudos efectuados incidiram sobre amostras representativas de lama, obtidas antes e após refinação e beneficiação a que foi submetida a lama tal-qual colhida nas salinas. Foram utilizados métodos geofísicos para caracterizar e distinguir as lamas depositadas na época de safra e no período de interregno. Para o efeito, foram cravados tubos amostradores no sedimento que reveste o fundo dos tanques, tubos que seguidamente foram transportados para o laboratório para medição da condutividade eléctrica do topo até à base da coluna de sedimento amostrado. A refinação foi efectuada por elutriação de suspensões aquosas de lama utilizando um equipamento desenvolvido para o efeito e que permitiu concentrar a lama fina no overflow. Após floculação, sifonagem da água sobrenadante, dessalinização e centrifugação a lama refinada e beneficiada pôde ser incorporada em formulações com objectivos terapêuticos e cosméticos. O estudo microbiológico efectuado nas amostras de lama com sal e sem sal e na água das salinas permitiu identificar diversos tipos de bactérias e colónias presentes na lama e avaliar também os processos de esterilização testados. Concluiu-se que a lama hipersalina ou dessalinizada resultante do processamento a que foram submetidas, não deve ser aplicada ou incorporada em formulações tal-qual, pelo facto de em ambas terem sido identificadas bactérias como é o caso de Clostridium perfringens. Não obstante, se submetidas a esterilização utilizando autoclave a lama salina refinada e beneficiada poderá ser aplicada como peloide extemporâneo. Assim sendo foram desenvolvidas formulações dermoterapêuticas e dermocosméticas contendo lama beneficiada e dessalinizada e esterilizada termicamente.

Detecting Submerged Macrophytes in a UK Chalk Stream Using Field Spectroscopy

Various studies using optical remote sensing in the marine environment have shown the possibilities of spectral discrimination of benthic macro and micro-algae. For in-land water bodies only very recently studies of have explored similar use of optical remote sensing to identify the taxonomic composition of algae and rooted plant communities. The importance of these communities for the functioning of river ecosystems warrants further research. In the study presented here, field spectroscopy is used to assess the possibilities of optically detecting macrophytes in a UK chalk streams. Spectral signatures of four common macrophytes were measured using a hand-held GER1500 spectroradiometer. Despite the strong absorption of near infrared in water, the results show that information on NIR can clearly contribute to the detection of submerged vegetation in shallow UK chalk stream environments. Observed spectra compare well with simulated submerged vegetation spectra, based on water absorption coefficients only. The field investigations, which were performed in the river Wylye, also indicate the confounding effects of specular reflection from riparian vegetation. The results of this study can inform remote sensing studies of the riverine environment using multi-spectral/low altitude sensors. Such larger scale studies will be highly beneficial for monitoring variation in chalk stream bioindicators, such as ranunculus.

Accessing Planktothrix species diversity and associated toxins using quantitative real-time PCR in natural waters

Tese de Doutoramento em Biologia apresentada à Faculdade de Ciências da Universidade do Porto, 2015.

Análise do comportamento sísmico da barragem de Luzzone: desenvolvimento de um programa de EF3D utilizando uma formulação em deslocamentos e pressões

Trabalho Final de Mestrado elaborado no Laboratório Nacional de Engenharia Civil (LNEC) para a obtenção do grau de Mestre em Engenharia Civil pelo Instituto Superior de Engenharia de Lisboa no âmbito do protocolo entre o ISEL e o LNEC

Effet de l'initiation du traitement antirétroviral sur la diversité virale du VIH

L’épidémie du VIH-1 dure maintenant depuis plus de 25 ans. La grande diversité génétique de ce virus est un obstacle majeur en vue de l’éradication de cette pandémie. Au cours des années, le VIH-1 a évolué en plus de cinquante sous-types ou formes recombinantes. Cette diversité génétique est influencée par diverses pressions de sélection, incluant les pressions du système immunitaire de l’hôte et les agents antirétroviraux (ARV). En effet, bien que les ARV aient considérablement réduit les taux de morbidité et de mortalité, en plus d’améliorer la qualité et l’espérance de vie des personnes atteintes du VIH-1, ces traitements sont complexes, dispendieux et amènent leur lot de toxicité pouvant mener à des concentrations plasmatiques sous-optimales pour contrôler la réplication virale. Ceci va permettre l’émergence de variantes virales portant des mutations de résistance aux ARV. Ce phénomène est encore plus complexe lorsque l’on prend en considération l’immense diversité génétique des différents sous-types. De plus, le virus du VIH est capable de persister sous forme latente dans diverses populations cellulaires, rendant ainsi son éradication extrêmement difficile. Des stratégies pouvant restreindre la diversité virale ont donc été préconisées dans le but de favoriser les réponses immunes de l’hôte pour le contrôle de l’infection et d’identifier des variantes virales offrant une meilleure cible pour des stratégies vaccinales ou immunothérapeutiques. Dans cet esprit, nous avons donc étudié, chez des sujets infectés récemment par le VIH-1, l’effet du traitement ARV précoce sur la diversité virale de la région C2V5 du gène enveloppe ainsi que sur la taille des réservoirs. En deuxième lieu, nous avons caractérisé la pression de sélection des ARV sur des souches virales de sous types variés non-B, chez des patients du Mali et du Burkina Faso afin d’évaluer les voies d’échappement viral dans un fond génétique différent du sous-type B largement prévalent en Amérique du Nord. Notre étude a démontré la présence d’une population virale très homogène et peu diversifiée dans les premières semaines suivant l’infection, qui évolue pour atteindre une diversification de +0,23% à la fin de la première année. Cette diversification est plus importante chez les sujets n’ayant pas initié de traitement. De plus, ceci s’accompagne d’un plus grand nombre de particules virales infectieuses dans les réservoirs viraux des cellules mononucléées du sang périphérique (PBMC) chez ces sujets. Ces résultats suggèrent que l’initiation précoce du traitement pourrait avoir un effet bénéfique en retardant l’évolution virale ainsi que la taille des réservoirs, ce qui pourrait supporter une réponse immune mieux ciblée et potentiellement des stratégies immunothérapeutiques permettant d’éradiquer le virus. Nous avons également suivi 801 sujets infectés par des sous-types non-B sur le point de débuter un traitement antirétroviral. Bien que la majorité des sujets ait été à un stade avancé de la maladie, plus de 75% des individus ont obtenu une charge virale indétectable après 6 mois d’ARV, témoignant de l’efficacité comparable des ARV sur les sous-types non-B et B. Toutefois, contrairement aux virus de sous-type B, nous avons observé différentes voies moléculaires de résistance chez les sous type non-B, particulièrement chez les sous-types AGK/AK/K pour lesquels les voies de résistances étaient associées de façon prédominante aux TAM2. De plus, bien que la divergence entre les virus retrouvés chez les patients d’une même région soit faible, nos analyses phylogénétiques ont permis de conclure que ces mutations de résistance se sont produites de novo et non à partir d’un ancêtre commun porteur de résistance. Cependant, notre dernière étude au Mali nous a permis d’évaluer la résistance primaire à près de 10% et des études phylogénétiques seront effectuées afin d’évaluer la circulation de ces souches résistantes dans la population. Ces études suggèrent qu’un contrôle de la réplication virale par les ARV peut freiner la diversité du VIH et ainsi ouvrir la voie à un contrôle immunologique ciblé, utilisant de nouvelles stratégies vaccinales ou immunothérapeutiques. Toutefois, une thérapie antirétrovirale sous-optimale (adhérence, toxicité) peut conduire à l’échappement virologique en favorisant l’émergence et la dissémination de souches résistantes.