Identification of TRIM22 single nucleotide polymorphisms associated with loss of inhibition of HIV-1 transcription and advanced HIV-1 disease

Silvia Ghezzi, Laura Galli, Anna Kajaste-Rudnitski, Filippo Turrini, Sara Marelli, Daniela Toniolo, Claudio Casoli, Agostino Riva, Guido Poli, Antonella Castagna, Elisa Vicenzi

Research output: Contribution to journalArticlepeer-review

Abstract

Objective(s): Tripartite motif-containing 22 (TRIM22) is an interferon-induced protein that inhibits HIV-1 transcription and replication in vitro. Two single nucleotide missense polymorphisms rs7935564A/G (SNP-1) and rs1063303C/G (SNP-2) characterize the coding sequence of human TRIM22 gene. We tested whether these variants affected the inhibitory effect of TRIM22 on HIV-1 replication and transcription and their potential association with HIV-1 disease. Design: The allelic discrimination was determined in 182 HIV-1-negative and among HIV-1-positive individuals with advanced disease progression (advanced progressors; n=57), normal progressors (n=76), and long-term nonprogressors (LTNPs; n=95). Methods: Renilla luciferase activity was measured after infection of activated peripheral blood mononuclear cells (PBMCs) from an additional group of 61 blood donors with a recombinant HIV-1. HIV-1-long terminal repeat (LTR)-driven luciferase activity was tested in the presence of plasmid expressing TRIM22 variants in 293T cells. The SNP genotyping was determined by TaqMan assay. Results: HIV-1 replication was more efficient in PBMCs from donors with SNP-1G and SNP-2G than from those with SNP-1A and SNP-2C alleles. Consistently, TRIM22-GG enhanced, whereas TRIM22-AC restricted basal HIV-1 LTR-driven transcription. In vivo, SNP-1G homozygotes and A/G heterozygotes were more frequent in advanced progressors than in LTNPs [odds ratio (OR)=2.072, P=0.005] or in normal progressors (OR=1.809, P=0.022); in contrast, SNP-2 was not associated with any state of HIV-1 disease progression. Although SNP-2 distribution was similar among the groups, TRIM22-GG haplotype was found more frequently in advanced progressors than in LTNPs (P=0.02). Conclusion: TRIM22 genetic diversity affects HIV-1 replication in vitro and it is a potentially novel determinant of HIV-1 disease severity.

Original languageEnglish
Pages (from-to)2335-2344
Number of pages10
JournalAIDS (London, England)
Volume27
Issue number15
DOIs
Publication statusPublished - Sep 24 2013

Keywords

  • HIV-1 disease
  • HIV-1 long terminal repeat-driven transcription
  • HIV-1 replication
  • Single nucleotide polymorphisms
  • Tripartite motif-containing 22

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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