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The TLR9 2848C/T Polymorphism Is Associated with the CMV DNAemia among HIV/CMV Co-Infected Patients.

ABSTRACT: Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns and are essential components of the host's innate immune response. The aim of this study was to determine the TLR9 genotype frequency and investigate the association between TLR9 polymorphisms and cytomegalovirus (CMV) DNAemia in human immunodeficiency virus (HIV)/CMV co-infected patients. A total of 205 HIV/CMV co-infected adults were screened for the presence of the four TLR9 polymorphisms (-1237T/C, -1486T/C, 1174G/A, and 2848C/T) by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Mutation presented in at least one allele of the TLR9 2848C/T single nucleotide polymorphism (SNP) was associated with the occurrence of CMV DNAemia among HIV-infected patients with CMV co-infection (p = 0.004). The level of CMV DNA was higher in patients who were homozygous recessive or heterozygous for the 2848C/T polymorphism compared with those who had a wild-type genotype for this polymorphism (p = 0.005). Mutation detected in at least one allele of this SNP was also associated with a lower interferon type β (IFN-β) concentration (p = 0.048), while no relationships between TLR9 -1237T/C, -1486T/C, and 1174G/A SNPs and CMV DNAemia were observed. Our findings suggest that the mutation present in at least one allele of the TLR9 2848C/T SNP may be associated with the active CMV infection in HIV/CMV co-infected subjects.

SUBMITTER: Jablonska A

PROVIDER: S-EPMC8470824 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Cytomegalovirus (CMV) viremia continues to cause significant morbidity and mortality in kidney transplant patients with clinical complications including organ rejection and death. Whole blood gene expression dynamics in CMV viremic patients from onset of DNAemia through convalescence has not been well studied to date in humans. To evaluate how CMV infection impacts whole blood leukocyte gene expression over time, we evaluated a matched cohort of 62 kidney transplant recipients with and without CMV DNAemia using blood samples collected at multiple time points during the 12-month period after transplant. While transcriptomic differences were minimal at baseline between DNAemic and non-DNAemic patients, hundreds of genes were differentially expressed at the long-term timepoint, including genes enriching for pathways important for macrophages, interferon, and IL-8 signaling. Amongst patients with CMV DNAemia, the greatest amount of transcriptomic change occurred between baseline and 1-week post-DNAemia, with increase in pathways for interferon signaling and cytotoxic T cell function. Time-course gene set analysis of these differentially expressed genes revealed that most of the enriched pathways had a significant time-trend. While many pathways that were significantly down- or upregulated at 1 week returned to baseline-like levels, we noted that several pathways important in adaptive and innate cell function remained upregulated at the long-term timepoint after resolution of CMV DNAemia. Differential expression analysis and time-course gene set analysis revealed the dynamics of genes and pathways involved in the immune response to CMV DNAemia in kidney transplant patients. Understanding transcriptional changes caused by CMV DNAemia may identify the mechanism behind patient vulnerability to CMV reactivation and increased risk of rejection in transplant recipients and suggest protective strategies to counter the negative immunologic impact of CMV. These findings provide a framework to identify immune correlates for risk assessment and guiding need for extending antiviral prophylaxis.

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The TLR9 2848C/T Polymorphism Is Associated with the CMV DNAemia among HIV/CMV Co-Infected Patients.

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