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- aggregation classification "C3".
- aggregation creator B46505.
- aggregation creator B46506.
- aggregation creator B46507.
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- aggregation date "2012".
- aggregation format "application/pdf".
- aggregation hasFormat 3236415.bibtex.
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- aggregation isPartOf urn:issn:1359-6535.
- aggregation language "eng".
- aggregation rights "I have retained and own the full copyright for this publication".
- aggregation subject "Biology and Life Sciences".
- aggregation title "Comprehensive characterization of LEDGF/p75 in a HIV-1 infected patient cohort".
- aggregation abstract "BACKGROUND: Lens epithelium derived growth factor interaction inhibitors (LEDGINs) are an emerging new class of allosteric integrase inhibitors. Few data is available about the genetic variability, mRNA and protein expression levels of LEDGF/p75 in HIV-1 infected patients. The present study evaluated the relation between LEDGF/p75 genetic variation, mRNA/protein expression levels and HIV-1 disease progression in order to further validate LEDGINs in clinical practice. METHODS: Samples were derived from a therapy-naïve cohort at the Ghent University Hospital and from the Spanish long-term-non-progressor cohort, kindly provided by the HIV BioBank integrated in the Spanish AIDS Research Network (RIS). High resolution melting curve analysis and Sanger sequencing were used to identify all single nucleotide polymorphisms (SNPs) in the coding region and 3’UTR of LEDGF/p75. We quantified LEDGF/p75 mRNA derived from patient PBMCs using RT-qPCR with validated reference genes for normalization. Western blotting was performed on selected samples. RESULTS: 325 samples were investigated, 291 (90%) of Caucasian and 34 (10%) of African origin and comprising Elite controllers (n=49) and Viremic controllers (n=62). We identified 24 SNPs, including 5 in the coding region (2 synonymous and 3 non-synonymous), 17 in the flanking non-coding regions and the 3’UTR, and two additional tagSNPs. The minor allele frequency of the SNPs in the coding region was very low and none of the variants had a major impact on protein structure according to SIFT and PolyPhen score. One intronic SNP (rs2737828, n=13) was significantly under-represented in Caucasian HIV patients (P<0.0001) compared to healthy controls (HapMap). No splice variants were detected. There was no correlation between mRNA expression levels of LEDGF/p75 and disease progression. Of note, low levels of protein expression as determined by western blot, did not exclude a high viral load. CONCLUSIONS: The data of this investigation support the idea that LEDGF/p75 might influence HIV susceptibility in Caucasians. Very low levels of LEDGF/p75, previously linked with decreased integration in transcriptional active regions in vitro, did however not result in lower viral load. As LEDGF/p75 expression levels differ substantially among patients, LEDGINs will have to compete with their cellular competitor for IN binding in case of high expression.".
- aggregation authorList BK117401.
- aggregation endPage "A83".
- aggregation issue "suppl. 1".
- aggregation startPage "A83".
- aggregation volume "17".
- aggregation aggregates 3236416.
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