Coregulation of HIV-1 dependency factors in individuals heterozygous to the CCR5-delta32 deletionReport as inadecuate




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AIDS Research and Therapy

, 10:26

First Online: 18 November 2013Received: 11 July 2013Accepted: 05 November 2013

Abstract

BackgroundCCR5-delta32 heterozygous individuals are susceptible to HIV-1. However, it is not clear if there is a relevant protective effect against transmission and a beneficial effect in terms of HIV progression which cannot be attributed to CCR5 surface density alone. Therefore we investigated HIV-1 dependency factors HDF which might be differently regulated in CCR5 wild type WT and CCR5-delta32 heterozygous individuals.

MethodsWe examined CD34+ hematopoietic progenitor cells derived from bone marrow samples from 19 healthy volunteers, 12 individuals with CCR5 WT and 7 with heterozygous CCR5-delta32 deletion. Samples were analyzed using a global gene expression oligonucleotide microarray HG-U133plus 2.0, Affymetrix Inc



ResultsA total of 205 genes were found with altered expression 3fold difference, present call rate of 75%, p < 0.05 and 7 of these had a connection to HIV-1 pathogenesis. In 4 genes: TOP1, CXCR2, SREBF2, and TAP we found a different regulation which was consistent with a supposed beneficial effect for CCR5-delta32 heterozygotes.

ConclusionThe CCR5-delta32 deletion is associated with other HDFs in HIV-1 pathogenesis as a possible explanation for beneficial effects regarding the deletion leading to a variant expression profile in heterozygous carriers of this mutation.

KeywordsCCR5-delta32 HIV-1 Coexpression TOP1 CXCR2 SREBF2 TAP Electronic supplementary materialThe online version of this article doi:10.1186-1742-6405-10-26 contains supplementary material, which is available to authorized users.

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Author: Gero Hütter - Christian Blüthgen - Martin Neumann - Mark Reinwald - Daniel Nowak - Harald Klüter

Source: https://link.springer.com/



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