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Updated: Apr 25, 2026

A Restriction Enzyme Based Cloning Method to Assess the In vitro Replication Capacity of HIV-1 Subtype C Gag-MJ4 Chimeric Viruses
Published on: August 31, 2014
Genetic variation in Trex1 affects HIV-1 disease progression
Thijs Booiman1, Laurentia C Setiawan, Neeltje A Kootstra
1Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory and Center for Infection and Immunity (CINIMA) at the Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
Objective:
Three prime repair exonuclease 1 (TREX1) plays a pivotal role in HIV-1 infection. In-vitro studies have shown that TREX1 degrades excess HIV-1 DNA, thereby shielding HIV-1 from recognition by innate immune receptors and preventing a type 1 interferon response. To determine whether TREX1 plays a role in HIV-1 pathogenesis, we analyzed whether genetic variation in Trex1 is associated with the clinical course of HIV-1 infection.
Design/Methods:
Two tagging single nucleotide polymorphisms (SNPs) in Trex1 were genotyped in a cohort of 304 HIV-1-infected MSM and a cohort of 66 high-risk seronegative individuals. Kaplan-Meier and Cox regression survival analyses were used to analyze the effect of the SNPs on HIV-1 disease progression. In-vitro HIV-1 infection assays and Trex1 mRNA analysis were performed in peripheral blood mononuclear cells (PBMCs) obtained from donors that were genotyped for the tag SNP in Trex1.
Results:
We observed that the minor allele of SNP rs3135941 in Trex1 is associated with faster HIV-1 disease progression. This association was independent of the CCR5-Δ32 genotype and human leukocyte antigen alleles that were previously found to be predictive of disease progression. In addition, we observed an increased HIV-1 replication in PBMC positive for the minor allele of SNP rs3135941.
Conclusion:
Our data emphasize the important role of TREX1 in HIV-1 pathogenesis. The association of SNP rs3135941 with accelerated disease progression that we observed might be explained by the increased HIV-1 replication observed in PBMC positive for the minor allele of the SNP.
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