Increased Levels of Human Beta-Defensins mRNA in Sexually HIV-1 Exposed But Uninfected Individuals

ABSTRACT: Protection against HIV-1 infection in exposed seronegative (ESN) individuals likely involves natural resistance mechanisms that have not been fully elucidated. Human beta defensins (HBD) are antimicrobial peptides found primarily in mucosae, the main ports of HIV entry. HBD-2 and 3 mRNA are induced by HIV-1 in human oral epithelial cells and exhibit strong anti-HIV-1 activity; in addition, polymorphisms in the DEFB1 gene, which encodes HBD-1, have been associated with resistance/susceptibility to different infections, including HIV-1. Here, we have assessed the association of HBD expression with the ESN phenotype. Peripheral blood and vaginal/endocervical and oral mucosal samples were taken from 47 ESN, 44 seropositive (SP) and 39 healthy controls (HC). HBD-1, 2 and 3 mRNA copy numbers were quantified by real time RT-PCR and A692G/G1654A/A1836G polymorphisms in the DEFB1 gene were detected by restriction fragment length polymorphisms and confirmed by nucleotide sequencing. ESN expressed significantly greater mRNA copy numbers of HBD-2 and 3 in oral mucosa than HC; p=0.0002 and p=0.007, respectively. mRNA copy numbers of HBD-1, 2 and 3 in vaginal/endocervical mucosa from ESN and HC were similar. Homozygosity for the A692G polymorphism was significantly more frequent in ESN (0.39) than in SP (0.05) (p=0.0002). In summary, ESN exhibited enhanced mucosal expression of the innate defense genes HBD-2 and 3; however, additional studies are required to verify these results and the potential association of the A692G polymorphism to the relative resistance of ESN to HIV-1 infection.

• Autores: Zapata Builes, Wildeman; Rugeles López, María Teresa; Rodríguez, Benigno; Lederman, Michael; Quiñones, Miguel; Zimmerman, Peter; Weber, Jan; Estrada, Hernando
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2008
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/36600
• Acceso en línea: https://hdl.handle.net/10495/36600
• Palabra clave: Polimorfismo Genético; Polymorphism, Genetic; Endometrio; Endometrium; Perfilación de la Expresión Génica; Gene Expression Profiling; Mucosa Bucal; Mouth Mucosa; Reacción en Cadena de la Polimerasa de Transcriptasa Inversa; Reverse Transcriptase Polymerase Chain Reaction; Análisis de Secuencia de ADN; Sequence Analysis, DNA; VIH-1; HIV-1
• Rights: openAccess
• License: http://creativecommons.org/licenses/by/2.5/co/