Identificación y caracterización de epítopos del rinovirus humano = $b Identification and characterization of Human Rhinovirus epitopes
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2023
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19/09/2022
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Universidad Complutense de Madrid
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Los rinovirus humanos (HRV) son los responsables de la mayor parte de infecciones del tracto respiratorio. En la mayoría de individuos, las infecciones por HRV son relativamente leves y se limitan al tracto respiratorio superior, siendo la causa más frecuente de resfriado común. Sin embargo, en algunos individuos, particularmente en niños pequeños e individuos que padecen enfermedades respiratorias crónicas o están inmunodeprimidos, los HRV pueden infectar el tracto respiratorio inferior, causando síntomas severos de bronquiolitis y neumonía. Como en cualquier infección viral, la inmunidad adaptativa frente a los HRV está mediada por linfocitos T y B, que reconocen regiones específicas en los antígenos conocidas como epítopos. Los esfuerzos iniciales en caracterizar la respuesta adaptativa frente a HRV se centraron en identificar epítopos B en las proteínas de la cápside que pudieran ser reconocidos por anticuerpos circulantes. Desafortunadamente, el genoma de los HRV es muy plástico, y las proteínas de la cápside son muy variables entre diferentes serotipos. De hecho, atendiendo específicamente a la variabilidad encontrada en estas proteínas de la cápside se han descrito más de 170 serotipos diferentes. Como resultado, los anticuerpos neutralizantes solo pueden reconocer epítopos específicos de cada serotipo, exhibiendo poca o nula reactividad cruzada entre distintos serotipos. En conjunto con los anticuerpos neutralizantes, los linfocitos T juegan un papel crucial en la inmunidad frente a HRV. Interesantemente, a pesar de la baja similitud entre las proteínas de HRV, se ha demostrado que los linfocitos T CD4 y CD8 sí pueden reconocer múltiples serotipos, revelando la existencia de epítopos T conservados de HRV. Hasta ahora, tan solo se habían identificado unos pocos epítopos T CD4 conservados de HRV y, sorprendentemente, no se conocía ningún epítopo T CD8 de HRV. La identificación de estos epítopos T conservados en múltiples serotipos de HRV sería de gran interés por varios motivos, incluyendo la monitorización de las infecciones por HRV y el diseño de vacunas...
Human rhinovirus (HRV) are the most frequent cause of viral respiratory tract infections worldwide. In most individuals, HRV infections are relatively mild and self-limited to the upper respiratory tract, being the most common cause of the common cold. However, in some subjects, particularly infants and individuals who suffer from chronic respiratory diseases or are immunocompromised, HRV can infect the lower respiratory tract, causing severe symptoms of bronchiolitis and pneumonia. As in any viral infection, adaptive immunity against HRV is mediated by B and T cells, which recognize specific sites in antigens known as epitopes. Initial efforts to characterize the adaptive immune response to HRV were aimed to identify B cell epitopes on capsid proteins, which could be targeted by neutralizing antibodies. Unfortunately, HRV genome is very plastic, and surface capsid proteins are particularly variable in different HRV strains. In fact, attending specifically to the variability found in these capsid proteins, over 170 distinct HRV serotypes have been described. As a result, neutralizing antibodies can only recognize serotype-specific epitopes, exhibiting little or no cross-reactivity between different serotypes. Along with neutralizing antibodies, T cells also play a crucial role in HRV immunity. Interestingly, despite the low sequence identity among HRV proteins, it has been shown that HRV-specific CD4 and CD8 T cells can be reactive to multiple HRV serotypes, revealing the presence of HRV-specific conserved T cell epitopes. So far, only a few conserved HRV-specific CD4 T epitopes had been identified and surprisingly, HRV-specific CD8 T cell epitopes remained yet to be identified. Identification of these conserved HRV-specific epitopes is of great interest for many reasons, including monitoring of HRV infections, understanding viral immunopathology and vaccine design...
Human rhinovirus (HRV) are the most frequent cause of viral respiratory tract infections worldwide. In most individuals, HRV infections are relatively mild and self-limited to the upper respiratory tract, being the most common cause of the common cold. However, in some subjects, particularly infants and individuals who suffer from chronic respiratory diseases or are immunocompromised, HRV can infect the lower respiratory tract, causing severe symptoms of bronchiolitis and pneumonia. As in any viral infection, adaptive immunity against HRV is mediated by B and T cells, which recognize specific sites in antigens known as epitopes. Initial efforts to characterize the adaptive immune response to HRV were aimed to identify B cell epitopes on capsid proteins, which could be targeted by neutralizing antibodies. Unfortunately, HRV genome is very plastic, and surface capsid proteins are particularly variable in different HRV strains. In fact, attending specifically to the variability found in these capsid proteins, over 170 distinct HRV serotypes have been described. As a result, neutralizing antibodies can only recognize serotype-specific epitopes, exhibiting little or no cross-reactivity between different serotypes. Along with neutralizing antibodies, T cells also play a crucial role in HRV immunity. Interestingly, despite the low sequence identity among HRV proteins, it has been shown that HRV-specific CD4 and CD8 T cells can be reactive to multiple HRV serotypes, revealing the presence of HRV-specific conserved T cell epitopes. So far, only a few conserved HRV-specific CD4 T epitopes had been identified and surprisingly, HRV-specific CD8 T cell epitopes remained yet to be identified. Identification of these conserved HRV-specific epitopes is of great interest for many reasons, including monitoring of HRV infections, understanding viral immunopathology and vaccine design...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, leída el 19-09-2022