RESUMO
Introduction: To date there has been no statistical evaluation of the profiles of immunoglobulin classes and viral replication as variables in the study of HTLV-1 infection and circulation among families in virus-endemic areas of Colombia. Objective: To evaluate the correlation of several immunological and molecular characteristics with the transmission and circulation of HTLV-1 among families in the town of Tumaco. Materials and methods: Plasma levels of HTLV-1 specific immunoglobulin classes IgG, IgM and IgA1, as well as IgG and sIgA in oral fluids, were calculated for 32 members of 10 family groups from Tumaco in which the mother and at least one child were infected with the virus. Levels of the different immunoglobulin classes were correlated with viral RNA circulating in plasma or oral fluids and the proviral burden as detected by RT-PCR. Results: Significant differences were determined between mothers and carrier children for immunoglobulin levels (p=0.037) and proviral burden (p=0.002). The overall estimate of IgG in plasma and sIgA in oral fluids could be correlated with the circulation of free viral RNA in both fluids and high proviral burden, and associated with HAM/TSP mothers. The detection of anti- tax IgG in plasma revealed differences between HAM/TSP mothers and their offspring. Conclusion: The study of immunological and molecular variables permitted the analysis of HTLV-1 circulation among families of Tumaco. The strong correlation between levels of IgM specific for the virus and viral RNA circulating in fluids indirectly confirmed the transmission of HTLV-1 among families.
Introducción. Todavía no hay una evaluación estadística de los perfiles de las clases de inmuno- globulina s y la replicación viral, como variables para estudiar la infección y la circulació n del HTLV-1 en familias de zonas endémicas en Colombia. Objetivo. Evaluar la correlación de varias características inmunológicas y moleculares, con la transmisión y circulación del virus en familias del municipio de Tumaco. Materiales y métodos. Se calcularon los niveles de IgG, IgM e IgA1 en plasma, e IgG y IgA secretoria en fluido oral, de 32 miembros de 10 grupos familiares de Tumaco, en los que la madre y, al menos, un hijo estaban infectados con el virus. La concentración de las diferentes clases de inmunoglobulinas se pudo correlacionar con la circulación de ARN viral libre en plasma y fluido oral, y la carga proviral, según su detección mediante reacción en cadena de la polimerasa de transcripción inversa. Resultados. Se encontraron diferencias significativas en los niveles de inmunoglobulinas (p=0,037) y en la carga proviral (p=0,002) entre madres e hijos portadores. La estimación total de IgG en plasma e IgA secretoria en fluido oral, se pudo correlacionar con la circulación de ARN viral libre en ambos fluidos y una alta carga proviral, y se asoció con las madres paraparesia espástica tropical o mielopatía asociada con el HTLV-1. La detección en plasma de IgG anti-Tax reveló diferencias entre ellas y sus hijos. Conclusión. El estudio de las variables inmunológicas y moleculares permitió analizar la circulación del HTLV-1 en familias de Tumaco. La fuerte asociación entre los niveles de IgM específica para el virus y el ARN viral circulante en los fluidos y la carga proviral, confirmó indirectamente la transmisión intrafamiliar del virus.
Assuntos
Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , RNA Viral/análise , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Anticorpos Anti-HTLV-I/análise , Infecções por HTLV-I/epidemiologia , Saúde da Família , Viremia/imunologia , Viremia/epidemiologia , Viremia/virologia , Aleitamento Materno/efeitos adversos , RNA Viral/sangue , Vírus Linfotrópico T Tipo 1 Humano/genética , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Anticorpos Anti-HTLV-I/sangue , Infecções por HTLV-I/imunologia , Infecções por HTLV-I/transmissão , Infecções por HTLV-I/virologia , Estudos Soroepidemiológicos , Estudos Transversais , Provírus/isolamento & purificação , Colômbia/epidemiologia , Transmissão Vertical de Doenças Infecciosas , Doenças Endêmicas , MãesRESUMO
INTRODUCTION: To date there has been no statistical evaluation of the profiles of immunoglobulin classes and viral replication as variables in the study of HTLV-1 infection and circulation among families in virus-endemic areas of Colombia. OBJECTIVE: To evaluate the correlation of several immunological and molecular characteristics with the transmission and circulation of HTLV-1 among families in the town of Tumaco. MATERIALS AND METHODS: Plasma levels of HTLV-1 specific immunoglobulin classes IgG, IgM and IgA1, as well as IgG and sIgA in oral fluids, were calculated for 32 members of 10 family groups from Tumaco in which the mother and at least one child were infected with the virus. Levels of the different immunoglobulin classes were correlated with viral RNA circulating in plasma or oral fluids and the proviral burden as detected by RT-PCR. RESULTS: Significant differences were determined between mothers and carrier children for immunoglobulin levels (p=0.037) and proviral burden (p=0.002). The overall estimate of IgG in plasma and sIgA in oral fluids could be correlated with the circulation of free viral RNA in both fluids and high proviral burden, and associated with HAM/TSP mothers. The detection of anti- tax IgG in plasma revealed differences between HAM/TSP mothers and their offspring. CONCLUSION: The study of immunological and molecular variables permitted the analysis of HTLV-1 circulation among families of Tumaco. The strong correlation between levels of IgM specific for the virus and viral RNA circulating in fluids indirectly confirmed the transmission of HTLV-1 among families.
Assuntos
Saúde da Família , Anticorpos Anti-HTLV-I/análise , Infecções por HTLV-I/epidemiologia , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , RNA Viral/análise , Adolescente , Adulto , Aleitamento Materno/efeitos adversos , Criança , Pré-Escolar , Colômbia/epidemiologia , Estudos Transversais , Doenças Endêmicas , Feminino , Anticorpos Anti-HTLV-I/sangue , Infecções por HTLV-I/imunologia , Infecções por HTLV-I/transmissão , Infecções por HTLV-I/virologia , Vírus Linfotrópico T Tipo 1 Humano/genética , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Humanos , Transmissão Vertical de Doenças Infecciosas , Masculino , Pessoa de Meia-Idade , Mães , Provírus/isolamento & purificação , RNA Viral/sangue , Estudos Soroepidemiológicos , Viremia/epidemiologia , Viremia/imunologia , Viremia/virologia , Adulto JovemRESUMO
Background: The information of gene expression obtained from databases, have made possible the extraction and analysis of data related with several molecular processes involving not only in brain homeostasis but its disruption in some neuropathologies; principally in Down syndrome and the Alzheimer disease. Objective: To correlate the levels of transcription of 19 genes located in the Down Syndrome Critical Region (DSCR) with their expression in several substructures of normal human brain. Methods: There were obtained expression profiles of 19 DSCR genes in 42 brain substructures, from gene expression values available at the database of the human brain of the Brain Atlas of the Allen Institute for Brain Sciences", (http://human.brain-map.org/). The co-expression patterns of DSCR genes in brain were calculated by using multivariate statistical methods. Results: Highest levels of gene expression were registered at caudate nucleus, nucleus accumbens and putamen among central areas of cerebral cortex. Increased expression levels of RCAN1 that encode by a protein involved in signal transduction process of the CNS were recorded for PCP4 that participates in the binding to calmodulin and TTC3; a protein that is associated with differentiation of neurons. That previously identified brain structures play a crucial role in the learning process, in different class of memory and in motor skills. Conclusion: The precise regulation of DSCR gene expression is crucial to maintain the brain homeostasis, especially in those areas with high levels of gene expression associated with a remarkable process of learning and cognition.
Introducción: La información de la expresión de genes consignada en bases de datos, ha permitido extraer y analizar información acerca procesos moleculares implicados tanto en la homeostasis cerebral y su alteración en algunas neuropatologías. Objetivos: Correlacionar los niveles de transcripción de 19 genes localizados en la región crítica del cromosoma 21, asociada a Síndrome de Down (DSCR), con la localización cerebral y su coexpresión en diferentes subestructuras del cerebro humano. Métodos: A partir de valores de expresión génica disponibles en la base de datos del proyecto cerebro humano del Atlas del Cerebro del "Allen Institute for Brain Sciences" (http://human.brain-map.org/), se construyeron perfiles de expresión de 19 genes DSCR en 42 subestructuras cerebrales. Además, utilizando métodos estadísticos multivariados se analizaron los patrones de coexpresión de genes DSCR en el cerebro normal. Resultados: En el núcleo caudado, el núcleo accumbens y el putamen además de las Áreas centrales 2, 3 y 4, se determinaron los valores de expresión más elevados para los genes incluidos RCAN1, que codifica para una proteína involucrada en el proceso de transducción de señales de SNC; PCP4 cuya proteína interviene en la unión a la calmodulina y TTC3 una proteína que interviene en la diferenciación de neuronas. Las subestructuras identificadas con una elevada expresión de estos genes, están asociadas con procesos de aprendizaje, en diferentes tipos de memoria y habilidades motoras. Conclusiones: La regulación de la expresión de los genes DSCR es clave para mantener la homeostasis cerebral, especialmente en aquellas áreas de mayor expresión, las cuales están asociadas con procesos sumamente importantes.
Assuntos
Humanos , Encéfalo/fisiologia , Síndrome de Down/genética , Expressão Gênica , Encéfalo/fisiopatologia , Diferenciação Celular , Bases de Dados Factuais , Homeostase , Análise Multivariada , Neurônios/metabolismoRESUMO
BACKGROUND: The information of gene expression obtained from databases, have made possible the extraction and analysis of data related with several molecular processes involving not only in brain homeostasis but its disruption in some neuropathologies; principally in Down syndrome and the Alzheimer disease. OBJECTIVE: To correlate the levels of transcription of 19 genes located in the Down Syndrome Critical Region (DSCR) with their expression in several substructures of normal human brain. METHODS: There were obtained expression profiles of 19 DSCR genes in 42 brain substructures, from gene expression values available at the database of the human brain of the Brain Atlas of the Allen Institute for Brain Sciences", (http://human.brain-map.org/). The co-expression patterns of DSCR genes in brain were calculated by using multivariate statistical methods. RESULTS: Highest levels of gene expression were registered at caudate nucleus, nucleus accumbens and putamen among central areas of cerebral cortex. Increased expression levels of RCAN1 that encode by a protein involved in signal transduction process of the CNS were recorded for PCP4 that participates in the binding to calmodulin and TTC3; a protein that is associated with differentiation of neurons. That previously identified brain structures play a crucial role in the learning process, in different class of memory and in motor skills. CONCLUSION: The precise regulation of DSCR gene expression is crucial to maintain the brain homeostasis, especially in those areas with high levels of gene expression associated with a remarkable process of learning and cognition.
INTRODUCCIÓN: La información de la expresión de genes consignada en bases de datos, ha permitido extraer y analizar información acerca procesos moleculares implicados tanto en la homeostasis cerebral y su alteración en algunas neuropatologías. OBJETIVOS: Correlacionar los niveles de transcripción de 19 genes localizados en la región crítica del cromosoma 21, asociada a Síndrome de Down (DSCR), con la localización cerebral y su coexpresión en diferentes subestructuras del cerebro humano. MÉTODOS: A partir de valores de expresión génica disponibles en la base de datos del proyecto cerebro humano del Atlas del Cerebro del "Allen Institute for Brain Sciences" (http://human.brain-map.org/), se construyeron perfiles de expresión de 19 genes DSCR en 42 subestructuras cerebrales. Además, utilizando métodos estadísticos multivariados se analizaron los patrones de coexpresión de genes DSCR en el cerebro normal. RESULTADOS: En el núcleo caudado, el núcleo accumbens y el putamen además de las Áreas centrales 2, 3 y 4, se determinaron los valores de expresión más elevados para los genes incluidos RCAN1, que codifica para una proteína involucrada en el proceso de transducción de señales de SNC; PCP4 cuya proteína interviene en la unión a la calmodulina y TTC3 una proteína que interviene en la diferenciación de neuronas. Las subestructuras identificadas con una elevada expresión de estos genes, están asociadas con procesos de aprendizaje, en diferentes tipos de memoria y habilidades motoras. CONCLUSIONES: La regulación de la expresión de los genes DSCR es clave para mantener la homeostasis cerebral, especialmente en aquellas áreas de mayor expresión, las cuales están asociadas con procesos sumamente importantes.
Assuntos
Encéfalo/fisiologia , Síndrome de Down/genética , Expressão Gênica , Encéfalo/fisiopatologia , Diferenciação Celular , Bases de Dados Factuais , Homeostase , Humanos , Análise Multivariada , Neurônios/metabolismoRESUMO
OBJETIVO: Caracterizar el ambiente genómico de las secuencias adyacentes al virus linfotrópico humano de células T tipo 1 (HTLV-1) en pacientes con paraparesia espßstica tropical y mielopatía asociada a la infección con HTLV-1 (PET/MAH) de diferentes regiones de Colombia y del Japón. MÉTODOS: Se enfrentaron 71 clones recombinantes con secuencias del genoma humano adyacentes al 5'-LTR de pacientes con PET/MAH, a las bases de datos del Genome Browser y del Gen-Bank. Se identificaron y analizaron estadísticamente 16 variables genómicas estructurales y composicionales mediante el programa informßtico R, versión 2.8.1, en una ventana de 0,5 Mb. RESULTADOS: El 43,0 por ciento de los provirus se localizaron en los cromosomas del grupo C; 74 por ciento de las secuencias se ubicaron en regiones teloméricas y subteloméricas (P < 0,05). Un anßlisis de conglomerados permitió establecer las relaciones jerßrquicas entre las características genómicas incluidas en el estudio; el anßlisis de componentes principales identificó las componentes que definieron los ambientes genómicos preferidos para la integración proviral en casos de PET/MAH. CONCLUSIONES: El HTLV-1 se integró con mayor frecuencia en regiones de la cromatina ricas en islas de citocina fosfato guanina (CpG), de alta densidad de genes y de repeticiones tipo LINE (elemento disperso largo [long interspersed element]) y transposones de ADN que, en conjunto, conformarían los ambientes genómicos blanco de integración. Este nuevo escenario promoverß cambios sustanciales en el campo de la salud pública y en el manejo epidemiológico de las enfermedades infecciosas, y permitirß desarrollar potentes herramientas para incrementar la eficiencia de la vigilancia epidemiológica.
OBJECTIVE: Characterize the genomic environment of the sequences adjacent to human T-cell lymphotropic virus type 1 (HTLV-1) in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in different regions of Colombia and Japan. METHODS: A total of 71 recombinant clones with human genome sequences adjacent to 5' LTR in patients with HAM/TSP were compared to the Genome Browser and GenBank databases. Sixteen structural and compositional genome variables were identified, and statistical analysis was conducted in the R computer program, version 2.8.1, in a 0.5 Mb window. RESULTS: A total of 43.0 percent of the proviruses were located in the group C chromosomes; 74 percent of the sequences were located in the telomeric and subtelomeric regions (P < 0.05). A cluster analysis was used to establish the hierarchical relations between the genome characteristics included in the study. The analysis of principal components identified the components that defined the preferred genome environments for proviral integration in cases of HAM/TSP. CONCLUSIONS: HTLV-1 was integrated more often in chromatin regions rich in CpG islands with a high density of genes and LINE type repetitions, and DNA transposons which, overall, would form the genomic environments targeted for integration. This new scenario will promote substantial changes in the field of public health and in epidemiological management of infectious diseases. It will also foster the development of powerful tools for increasing the efficiency of epidemiological surveillance.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Genoma Humano , Vírus Linfotrópico T Tipo 1 Humano/genética , Paraparesia Espástica Tropical/genética , Provírus/genética , Sequências Repetidas Terminais/genética , Integração Viral/genética , Mapeamento Cromossômico , Cromossomos Humanos/genética , Colômbia/epidemiologia , Ilhas de CpG , DNA Recombinante/genética , Paraparesia Espástica Tropical/epidemiologia , Paraparesia Espástica Tropical/virologia , Retroelementos/genética , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência do Ácido NucleicoRESUMO
Although the infection of HTLV-1 to cell components of the mouth have been previously reported, there was not until this report, a detailed study to show the characteristics of such infection. From 14 Tropical Spastic Paraparesis/ HTLV-1-Associated Myelopathy (HAM/TSP) patients and 11 asymptomatic carrier individuals (AC) coming from HTLV-1 endemic areas of southwest Pacific of Colombia, infected oral mucosa cells were primary cultured during five days. These cell cultures were immunophenotyped by dual color fluorescence cell assortment using different lymphocyte CD markers and also were immunohistochemically processed using a polyclonal anti-keratin antibody. Five days old primary cultures were characterized as oral keratinocytes, whose phenotype was CD3- /CD4-/CD8-/CD19-/CD14-/CD45-/A575-keratin+. From DNA extracted of primary cultures LTR, pol, env and tax HTLV-1 proviral DNA regions were differentially amplified by PCR showing proviral integration. Using poly A+ RNA obtained of these primary cultures, we amplify by RT-PCR cDNA of tax and pol in 57.14 percent (8/14) HAM/TSP patients and 27.28 percent (3/11) AC. Tax and pol poly A+ RNA were expressed only in those sIgA positive subjects. Our results showed that proviral integration and viral gene expression in oral keratinocytes are associated with a HTLV-1 specific local mucosal immune response only in those HTLV-1 infected individuals with detectable levels of sIgA in their oral fluids. Altogether the results gave strong evidence that oral mucosa infection would be parte of the systemic spreading of HTLV-1 infection.
Assuntos
Humanos , Anticorpos Antideltaretrovirus , HIV , Imuno-Histoquímica , Imunofenotipagem , Técnicas In Vitro , Queratinócitos , Reação em Cadeia da Polimerase , Vírus da Reticuloendoteliose , Infecções Tumorais por Vírus , Métodos , PacientesRESUMO
OBJECTIVE: Characterize the genomic environment of the sequences adjacent to human T-cell lymphotropic virus type 1 (HTLV-1) in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in different regions of Colombia and Japan. METHODS: A total of 71 recombinant clones with human genome sequences adjacent to 5' LTR in patients with HAM/TSP were compared to the Genome Browser and GenBank databases. Sixteen structural and compositional genome variables were identified, and statistical analysis was conducted in the R computer program, version 2.8.1, in a 0.5 Mb window. RESULTS: A total of 43.0% of the proviruses were located in the group C chromosomes; 74% of the sequences were located in the telomeric and subtelomeric regions (P < 0.05). A cluster analysis was used to establish the hierarchical relations between the genome characteristics included in the study. The analysis of principal components identified the components that defined the preferred genome environments for proviral integration in cases of HAM/TSP. CONCLUSIONS: HTLV-1 was integrated more often in chromatin regions rich in CpG islands with a high density of genes and LINE type repetitions, and DNA transposons which, overall, would form the genomic environments targeted for integration. This new scenario will promote substantial changes in the field of public health and in epidemiological management of infectious diseases. It will also foster the development of powerful tools for increasing the efficiency of epidemiological surveillance.
Assuntos
Genoma Humano , Vírus Linfotrópico T Tipo 1 Humano/genética , Paraparesia Espástica Tropical/genética , Provírus/genética , Sequências Repetidas Terminais/genética , Integração Viral/genética , Adulto , Idoso , Mapeamento Cromossômico , Cromossomos Humanos/genética , Colômbia/epidemiologia , Ilhas de CpG , DNA Recombinante/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paraparesia Espástica Tropical/epidemiologia , Paraparesia Espástica Tropical/virologia , Retroelementos/genética , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência do Ácido NucleicoRESUMO
Although the infection of HTLV-1 to cell components of the mouth have been previously reported, there was not until this report, a detailed study to show the characteristics of such infection. From 14 Tropical Spastic Paraparesis/HTLV-1-Associated Myelopathy (HAM/TSP) patients and 11 asymptomatic carrier individuals (AC) coming from HTLV-1 endemic areas of southwest Pacific of Colombia, infected oral mucosa cells were primary cultured during five days. These cell cultures were immunophenotyped by dual color fluorescence cell assortment using different lymphocyte CD markers and also were immunohistochemically processed using a polyclonal anti-keratin antibody. Five days old primary cultures were characterized as oral keratinocytes, whose phenotype was CD3- /CD4-/CD8-/CD19-/CD14-/CD45-/A575-keratin+. From DNA extracted of primary cultures LTR, pol, env and tax HTLV-1 proviral DNA regions were differentially amplified by PCR showing proviral integration. Using poly A+ RNA obtained of these primary cultures, we amplify by RT-PCR cDNA of tax and pol in 57.14% (8/14) HAM/TSP patients and 27.28% (3/11) AC. Tax and pol poly A+ RNA were expressed only in those sIgA positive subjects. Our results showed that proviral integration and viral gene expression in oral keratinocytes are associated with a HTLV-1 specific local mucosal immune response only in those HTLV-1 infected individuals with detectable levels of sIgA in their oral fluids. Altogether the results gave strong evidence that oral mucosa infection would be parte of the systemic spreading of HTLV-1 infection.
Assuntos
Vírus Linfotrópico T Tipo 1 Humano , Integração Viral , Linfócitos , Genoma Humano , Epidemiologia Molecular , Colômbia , Integração Viral , Linfócitos , Genoma , Humanos , Paraparesia , Epidemiologia Molecular , Vírus Linfotrópico T Tipo 1 Humano , Paraparesia Espástica Tropical , Provírus , Sequências Repetidas Terminais , Mapeamento Cromossômico , Cromossomos Humanos , Colômbia , Ilhas de CpG , DNA Recombinante , Retroelementos , Alinhamento de Sequência , Análise de Sequência de DNA , Vírus Linfotrópico T Tipo 1 Humano , Integração Viral , Homologia de Sequência do Ácido NucleicoRESUMO
Introducción: La mayor parte del genoma celular es accesible a la integración retroviral; sin embargo, se propone que este proceso no es aleatorio y es dependiente de cada retrovirus. Objetivos: Identificar y caracterizar las regiones del genoma humano en donde ocurre la integración del virus de la inmunodeficiencia humana de tipo 1 (VIH-1) en células mononucleares de sangre periférica, macrófagos y células T de Jurkat infectadas. Materiales y métodos: Se seleccionaron 300 secuencias de ADN humano obtenidas por el método de ligación mediada por PCR, previamente depositadas en el GenBank. Utilizando el programa BLAST, sólo 264 de ellas se incluyeron en el estudio, pues se pudo obtener información sobre localización cromosómica, genes anotados, secuencias repetidas, número de islas CpG y tiempo medio de replicación, entre otras variables genómicas. Estas secuencias se exportaron a otras bases de datos. Resultados: El 53% (140/264) de las integraciones se registraron en bandas G. El 70,45% de los provirus se localizaron en los genes humanos anotados, mientras que el restante lo hizo en elementos repetidos. En general, la selección del sitio de integración se relacionó con las características locales genómicas y estructurales de la cromatina, entre las que se incluyen secuencias Alu-Sx y L1, densidad génica y de islas CpG, remodelación de la cromatina y tiempo de replicación. Éstas influenciarían la interacción eficiente del complejo de preintegración con los genomas celulares. Conclusión: Se determinó que la integración del VIH-1 en los genomas celulares estudiados estaría condicionada por características diferenciales de la cromatina y por procesos epigenéticos que influirían la selección del sitio blanco de integración.
Introduction: Most of the infected host cell genome is available for retroviral integration; however, it has been proposed that this process does not occur at random and depends upon each type of retrovirus. Objective: The objective is to identify and characterize differences in human genome regions of peripheral blood mononuclear cells, macrophages and Jurkat T cells in which integration of HIV-1 occurs. Material and Methods: Three hundred human DNA genome sequences, previously deposited in the GenBank, were selected at random. Using program BLAST, only 264 of them were included in the study because relevant information about chromosomal position, associated genes, repetitive sequences, number of CpG islands and average replication time was available; these sequences were exported to other data bases for analysis. Results: 53% (140/264) of integrations were located on G bands. 70.45% of provirus was located in human genes and the rest was located in repetitive elements. In general the integration site selection was correlated with genomics and structural characteristics of cell chromatin including Alu-Sx and L1 sequences, gene and CpG island densities, remodeling of chromatin, and replication time. All of them would influence the efficient interaction between the pre-integration complex and target cell genomes. Conclusion: It was determined that HIV-1 integration in target cellular genomes would be conditioned by differential characteristics of associated chromatin and by epigenetic processes that would influence the selection of integration sites.