Influencia de los haplotipos del CCR5-CCR2 en la transmisión sexual de la infección por HIV-1 en parejas discordantes que viven en la República Argentina
Acquired Immunodeficiency Syndrome (AIDS) was described over thirty years ago and human immunodeficiency virus (HIV) considered as its causative agent. Infection involves interaction between viral cover glycoproteins gp120/41 and molecules that belong to the Cluster of Differentiation group 4 (CD4)...
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Facultad de Farmacia y Bioquímica
2016
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_1666 http://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_1666.dir/1666.PDF |
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I28-R145-HWA_1666 |
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dspace |
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Universidad de Buenos Aires |
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I-28 |
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R-145 |
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Repositorio Digital de la Universidad de Buenos Aires (UBA) |
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Español |
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spa |
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HIV CCR5 CCR2 Parejas discordantes SIDA Argentina Ciencia de la vida |
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HIV CCR5 CCR2 Parejas discordantes SIDA Argentina Ciencia de la vida Paradiso, Patricia Influencia de los haplotipos del CCR5-CCR2 en la transmisión sexual de la infección por HIV-1 en parejas discordantes que viven en la República Argentina |
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HIV CCR5 CCR2 Parejas discordantes SIDA Argentina Ciencia de la vida |
| description |
Acquired Immunodeficiency Syndrome (AIDS) was described over thirty years ago and human immunodeficiency virus (HIV) considered as its causative agent. Infection involves interaction between viral cover glycoproteins gp120/41 and molecules that belong to the Cluster of Differentiation group 4 (CD4) expressed over target cells´ surface: T lymphocytes, macrophages and dendritic cells. This event is closely followed by the binding to a cellular chemokine receptor (CCR): CCR5 and/or CXCR4, to allow according tropism, fixation and viral incoming to the cell.\nFor establishing the relationship between the presence of co-receptor genes´ mutations with susceptibility or protection against infection, we recruited heterosexual couples whose members should be infected and non- infected, maintaining unprotected sexual intercourse within argentine population. They are known as discordant, serodiscordant or with mixed serological condition. Both members of these couples were serologically screened for detecting antigens and antibodies against HIV, HVB (Hepatitis B Virus), HCV (Hepatitis C Virus) and HTLV (Human T Lymphotropic Virus) at the beginning and ending of this protocol.\nOur main aim was to settle down the consequence of differences in CCR5-CCR2 haplotypes co-receptors´ over HIV infection in discordant Argentinean heterosexual couples and as secondary aims to detect other viral infections (HBV, HCV y HTLV) in the whole group; to compare allelic, haplotypic and haplotypic combinations frequencies of these co-receptors between infected and uninfected members of the couples and with Argentinean population control group and to compare these results with those obtained for the same genetic markers in perinatal transmission.\nWe developed an observational, descriptive, cohort, double blind study. Seronegative exposed (SNE) and seropositive (SP) individuals from heterosexual Argentinean couples were recruited. Haplotype characterization was done through PCR (Polymerase Chain Reaction) and RFLP-PCR (Restriction Fragment Length Polymorphism).\nBoth members of 63 heterosexual discordant couples were included. Some partners decided not to concur to the interviews but seven SP women, one SP man and one SNE woman confirmed their discordant partner?s condition and were included. All of them are adults, living in the República Argentina, signed informed consent and received wide information about this investigation aims. The protocol´s development period was: minimum lapse one year, maximum lapse five years (?=2.53 years ± SD=1.22). SPs are 40 women and 31 men and SNEs are 31 women and 33 men, no statistical differences between both cohorts were described according sex. 99 blood donors from argentine population from the ?Banco de Sangre del Hospital J. P. Garrahan? were established as control group (CG).\nCo-infection analysis revealed that SP´s frequencies were significantly higher (23.9%) when compared with SNE (3.1%) (p=0.0005, RR=7.66 IC 95% = 1.84-31.88). Comparing SNE with Argentinean population frequencies or SP with HIV reactive patients no significant differences were detected.\nHHG2 (?32) was the only one haplotype that showed statistical importance comparing SNE and CG (OR = 5.92 IC 95%: 1.59-21.99, p=0.0045). SP vs. CG and SP vs. SNE were not significantly different.\nHHE/HHE genotype was associated with greater infection risks and HHE/HHF2 showed protector effect (HHE/HHE: OR=5.09 IC (95%) 1.05-24.63, p=0.0428; HHE/HHF2: OR=0.13 IC (95%) 0.03-0.50, p=0.0039. These results agree with those reported for perinatal transmission in our population.\nIn this study we could demonstrate through genotyping CCR5-CCR2 haplotypes of HIV co receptors and their possible combinations in serodiscordant couples belonging to Argentinean population, that there is significant association with a predisposing factor: HHE/HHE and a protector one: HHE/HHF2. This analysis´ value resides over the fact that there are no publications on this subject made in our population until these days and that recruitment of these couples of difficult access, allowed us to recognize factors that may condition susceptibility to infection.\nInfection is the consequence of intercurrent factors involving host and virus; we cannot fail to mention that genetic variability of these co receptors is only one single event within conditioning possibilities of viral transmission. |
| author2 |
Sen, Luisa |
| author_facet |
Sen, Luisa Paradiso, Patricia |
| format |
Tesis de maestría Tesis de maestría acceptedVersion |
| author |
Paradiso, Patricia |
| author_sort |
Paradiso, Patricia |
| title |
Influencia de los haplotipos del CCR5-CCR2 en la transmisión sexual de la infección por HIV-1 en parejas discordantes que viven en la República Argentina |
| title_short |
Influencia de los haplotipos del CCR5-CCR2 en la transmisión sexual de la infección por HIV-1 en parejas discordantes que viven en la República Argentina |
| title_full |
Influencia de los haplotipos del CCR5-CCR2 en la transmisión sexual de la infección por HIV-1 en parejas discordantes que viven en la República Argentina |
| title_fullStr |
Influencia de los haplotipos del CCR5-CCR2 en la transmisión sexual de la infección por HIV-1 en parejas discordantes que viven en la República Argentina |
| title_full_unstemmed |
Influencia de los haplotipos del CCR5-CCR2 en la transmisión sexual de la infección por HIV-1 en parejas discordantes que viven en la República Argentina |
| title_sort |
influencia de los haplotipos del ccr5-ccr2 en la transmisión sexual de la infección por hiv-1 en parejas discordantes que viven en la república argentina |
| publisher |
Facultad de Farmacia y Bioquímica |
| publishDate |
2016 |
| url |
http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_1666 http://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_1666.dir/1666.PDF |
| work_keys_str_mv |
AT paradisopatricia influenciadeloshaplotiposdelccr5ccr2enlatransmisionsexualdelainfeccionporhiv1enparejasdiscordantesquevivenenlarepublicaargentina |
| _version_ |
1766017481537748992 |
| spelling |
I28-R145-HWA_16662019-09-27 Acquired Immunodeficiency Syndrome (AIDS) was described over thirty years ago and human immunodeficiency virus (HIV) considered as its causative agent. Infection involves interaction between viral cover glycoproteins gp120/41 and molecules that belong to the Cluster of Differentiation group 4 (CD4) expressed over target cells´ surface: T lymphocytes, macrophages and dendritic cells. This event is closely followed by the binding to a cellular chemokine receptor (CCR): CCR5 and/or CXCR4, to allow according tropism, fixation and viral incoming to the cell.\nFor establishing the relationship between the presence of co-receptor genes´ mutations with susceptibility or protection against infection, we recruited heterosexual couples whose members should be infected and non- infected, maintaining unprotected sexual intercourse within argentine population. They are known as discordant, serodiscordant or with mixed serological condition. Both members of these couples were serologically screened for detecting antigens and antibodies against HIV, HVB (Hepatitis B Virus), HCV (Hepatitis C Virus) and HTLV (Human T Lymphotropic Virus) at the beginning and ending of this protocol.\nOur main aim was to settle down the consequence of differences in CCR5-CCR2 haplotypes co-receptors´ over HIV infection in discordant Argentinean heterosexual couples and as secondary aims to detect other viral infections (HBV, HCV y HTLV) in the whole group; to compare allelic, haplotypic and haplotypic combinations frequencies of these co-receptors between infected and uninfected members of the couples and with Argentinean population control group and to compare these results with those obtained for the same genetic markers in perinatal transmission.\nWe developed an observational, descriptive, cohort, double blind study. Seronegative exposed (SNE) and seropositive (SP) individuals from heterosexual Argentinean couples were recruited. Haplotype characterization was done through PCR (Polymerase Chain Reaction) and RFLP-PCR (Restriction Fragment Length Polymorphism).\nBoth members of 63 heterosexual discordant couples were included. Some partners decided not to concur to the interviews but seven SP women, one SP man and one SNE woman confirmed their discordant partner?s condition and were included. All of them are adults, living in the República Argentina, signed informed consent and received wide information about this investigation aims. The protocol´s development period was: minimum lapse one year, maximum lapse five years (?=2.53 years ± SD=1.22). SPs are 40 women and 31 men and SNEs are 31 women and 33 men, no statistical differences between both cohorts were described according sex. 99 blood donors from argentine population from the ?Banco de Sangre del Hospital J. P. Garrahan? were established as control group (CG).\nCo-infection analysis revealed that SP´s frequencies were significantly higher (23.9%) when compared with SNE (3.1%) (p=0.0005, RR=7.66 IC 95% = 1.84-31.88). Comparing SNE with Argentinean population frequencies or SP with HIV reactive patients no significant differences were detected.\nHHG2 (?32) was the only one haplotype that showed statistical importance comparing SNE and CG (OR = 5.92 IC 95%: 1.59-21.99, p=0.0045). SP vs. CG and SP vs. SNE were not significantly different.\nHHE/HHE genotype was associated with greater infection risks and HHE/HHF2 showed protector effect (HHE/HHE: OR=5.09 IC (95%) 1.05-24.63, p=0.0428; HHE/HHF2: OR=0.13 IC (95%) 0.03-0.50, p=0.0039. These results agree with those reported for perinatal transmission in our population.\nIn this study we could demonstrate through genotyping CCR5-CCR2 haplotypes of HIV co receptors and their possible combinations in serodiscordant couples belonging to Argentinean population, that there is significant association with a predisposing factor: HHE/HHE and a protector one: HHE/HHF2. This analysis´ value resides over the fact that there are no publications on this subject made in our population until these days and that recruitment of these couples of difficult access, allowed us to recognize factors that may condition susceptibility to infection.\nInfection is the consequence of intercurrent factors involving host and virus; we cannot fail to mention that genetic variability of these co receptors is only one single event within conditioning possibilities of viral transmission. Fil: Paradiso, Patricia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Buenos Aires, Argentina Sen, Luisa Facultad de Farmacia y Bioquímica Mangano, Andrea Paradiso, Patricia 2016-10-18 El Síndrome de Inmunodeficiencia Adquirida ha sido descripto hace 30 años y el Virus de la Inmunodeficiencia Humana (HIV) identificado como su agente causal. La infección por HIV-1 involucra la interacción entre las glicoproteínas de la cubierta viral gp120/41 y las moléculas del grupo de diferenciación 4 (CD4) expresadas en la superficie de las células hospedadoras: linfocitos T, macrófagos y células dendríticas. Este evento es seguido de la unión a un receptor celular de quimioquinas (CCR): CCR5 y /o CXCR4, que permite la fijación y el subsecuente ingreso del virus según su tropismo.\nPara relacionar la presencia de mutaciones en los genes que codifican estos correceptores con la susceptibilidad o protección frente a la infección, se reclutaron parejas heterosexuales de población argentina en las que una persona es HIV positiva y la otra HIV negativa, aun manteniendo condiciones de sexo no protegido. Se las conoce como parejas ?discordantes?, ?serodiscordantes? o ?con estado serológico mixto?. Se sometió a ambos miembros de estas parejas a tamizaje serológico para la detección de antígenos y anticuerpos presentes en infecciones por HIV, HBV (Virus de la Hepatitis B), HCV (Virus de la Hepatitis C) y HTLV (Virus Linfotrópico T del Humano) al ingresar y finalizar el protocolo.\nNuestro objetivo principal fue analizar la influencia de los haplotipos en los correceptores del HIV-1: CCR5-CCR2 en población de parejas discordantes que viven en Argentina y secundariamente detectar infección y coinfección por otros patógenos virales (HBV, HCV y HTLV) en ambas cohortes, comparar las frecuencias alélicas, haplotípicas y de combinaciones de haplotipos de los correceptores obtenidas en la cohorte de infectados (seropositivos) , no infectados (expuestos seronegativos) y las del grupo control; y finalmente comparar los resultados obtenidos en estas parejas con los datos de estos marcadores para transmisión perinatal en nuestra población.\nDesarrollamos un estudio observacional, descriptivo, de cohortes, a doble ciego; para el cual se reclutaron individuos expuestos seronegativos (ESN) e individuos seropositivos (SP) miembros de parejas heterosexuales discordantes, adultos, que pertenecen a población argentina y mantenían sexo no protegido. La caracterización de los haplotipos se realizó mediante PCR y PCR-RFLP (Reacción en Cadena de la Polimerasa ? Longitud del polimorfismo de los fragmentos de restricción).\nIncluimos ambos integrantes de 63 parejas heterosexuales discordantes. Siete mujeres y un hombre seropositivo y una mujer seronegativa no concurrieron con su compañero, pero acreditaron su condición de discordante, por lo tanto fueron incluidos en este protocolo. Todos son adultos que viven en la República Argentina, firmaron el consentimiento informado y recibieron información exhaustiva sobre los objetivos de esta investigación. El período de desarrollo de este estudio fue: mínimo de un año y máximo de cinco años (?=2,53 años ± SD=1,22). La cohorte de seropositivos (SP) está compuesta por 40 mujeres y 31 hombres y la de expuestos seronegativos (ESN) por 31 mujeres y 33 hombres. No hallamos diferencias significativas entre ambas cohortes con respecto al sexo. Como ?grupo control? (GP) se incluyeron 99 donantes de sangre de población argentina que concurrieron al Banco de Sangre del Hospital J. P. Garrahan.\nEl análisis de las coinfecciones evidenció que las frecuencias fueron: significativamente mayores en SP (23,9%) con respecto a ESN (3,1%) (p=0,0005, RR= 7,66 IC 95% = 1,84-31,88) entre los miembros de ambas cohortes. No se encontraron diferencias significativas comparando los resultados de ESN con las prevalencias de estas patologías en población general argentina ni entre las frecuencias de coinfección de SP con las de la población general de pacientes HIV reactivos.\nEl único haplotipo que evidenció diferencia significativa entre ESN y GC fue HHG2 (??32) (OR = 5,92 IC 95%: 1,59-21,99, p=0,0045). Comparando SP vs. GC y SP vs. ESN no se evidencian diferencias significativas. El genotipo HHE/HHE se asocia en forma significativa con mayor riesgo de infección mientras que HHE/HHF2 con un efecto protector (HHE/HHE: OR=5,09 IC (95%) 1,05-24,63, p=0,0428; HHE/HHF2: OR=0,13 IC (95%) 0,03-0,50, p=0,0039. Estos resultados coinciden con los reportados para transmisión perinatal en población argentina.\nEn este estudio hemos demostrado mediante la genotipificación de los haplotipos CCR5-CCR2 y sus posibles combinaciones, que existe asociación significativa con un factor predisponente HHE/HHE y otro protector HHE/HHF2 frente a la infección por el virus HIV en parejas discordantes de población argentina. El valor de este análisis radica en el hecho que hasta el momento no hay publicaciones sobre este tema en nuestra población y que el reclutamiento de estas parejas de difícil acceso nos permite estudiar posibles factores que condicionan la susceptibilidad a la infección por HIV.\nLa infección es el resultado de la intercurrencia de características tanto del hospedador como del virus, por lo tanto no podemos dejar de mencionar que el análisis de la variabilidad de estos correceptores es sólo un aspecto dentro del universo de posibilidades condicionantes de la transmisión viral. application/pdf Quarleri, Jorge Benetucci, Jorge Gomez Carrillo, Manuel HIV CCR5 CCR2 Parejas discordantes SIDA Argentina spa Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/2.5/ar/ Ciencia de la vida Influencia de los haplotipos del CCR5-CCR2 en la transmisión sexual de la infección por HIV-1 en parejas discordantes que viven en la República Argentina info:eu-repo/semantics/masterThesis info:ar-repo/semantics/tesis de maestría info:eu-repo/semantics/acceptedVersion http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_1666 http://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_1666.dir/1666.PDF |