Article
Interferon-lambda 3 and 4 Polymorphisms Increase Sustained Virological Responses and Regulate Innate Immunity in Antiviral Therapy With Pegylated Interferon-Alpha
Registro en:
SILVA, Andréa Marques Vieira da et al. Interferon-lambda 3 and 4 Polymorphisms Increase Sustained Virological Responses and Regulate Innate Immunity in Antiviral Therapy With Pegylated Interferon-Alpha. Frontiers in cellular and infection microbiology, v. 11, p. 1-12, 2021
2235-2988
10.3389/fcimb.2021.656393
Autor
Silva, Andréa Marques Vieira da
Alvarado-Arnez, Lucia Elena
Azamor, Tamiris
Batista-Silva, Leonardo Ribeiro
Leal-Calvo, Thyago
Bezerra, Ohanna Cavalcanti de Lima
Ribeiro-Alves, Marcelo
Kehdy, Fernanda de Souza Gomes
Neves, Patrícia Cristina da Costa
Bayma, Camilla
Silva, Jane da
Souza, Alessandro Fonseca de
Muller, Marcelo
Andrade, Elisabete Ferreira de
Andrade, Ana Carolina Magalhães
Santos, Eliane Matos dos
Xavier, Janaína Reis
Maia, Maria De Lourdes De Sousa
Meireles, Rolando Páez
Cuni, Hugo Nodarse
Sander, Guilherme Becker
Picon, Paulo Dornelles
Matos, Denise C. S.
Moraes, Milton Ozório
Resumen
Sustained virologic response (SVR) in chronic hepatitis C (CHC) treatment denotes that the host genetics controls the immune response and unequivocally contribute to viral clearance or disease severity. In this context, single nucleotide polymorphisms (SNPs) in the locus of interferon lambda 3 and 4 genes (IFNL3/4) have been important genetic markers of responsiveness to CHC as prognostic markers for the pegylated-Interferon-alpha/ribavirin (Peg-IFN-α/RBV). Here, we analyzed 12 SNPs at the IFNL3/4 region in 740 treatment-naïve patients with CHC infected with hepatitis C virus (HCV) genotypes 1, 2, or 3 treated with Peg-IFN-α/RBV. Individually, rs12979860-CC, rs8109886-CC, or rs8099917-TT were predictive markers of SVR, while rs12979860-CC demonstrated the stronger effect. Besides, the genotypic combination of these three predictors' genotypes, CC/CC/TT, increased the rate of SVR. Serum levels of cytokines and gene expression analysis on the genes IFNL3, IFNL4, IFNA1, and some of the IFN-stimulated genes (ISGs) were measured in a subgroup of 24 treated patients and 24 healthy volunteers. An antagonist effect was highlighted between the expression of IFNL3/4 and IFNA1 mRNA among patients. Besides, a prominent production of the pro-inflammatory chemokines CCL4 and CXCL10 was observed at a 12-week treatment follow-up. Lower serum levels of these chemokines were detected in patients with an rs12979860-CC genotype associated with the better treatment outcome. Also, lower expression levels of the IFI6, IFI16, IRF9 genes were observed among rs12979860-CC individuals. In conclusion, a combination of the genotypes at the IFNL3/4 locus can act as a better marker for the prognosis for virological responses in an admixed Brazilian population presenting the modulating effect over innate immunity and inflammation that are controlling the outcome of the viral infection, but also other infectious diseases.