kjh The Korean Journal of Hematology Korean J Hematol 1738-7949 2092-9129 Korean Society of Hematology 10.5045/kjh.2007.42.1.33 kjh-42-33 Original Article Differentially Expressed Cellular Gene Profiles between Healthy HIV-infected Koreans and AIDS Patients ChoiJang-Hoon ChoiByeong-Sun KimSung Soon LeeJoo-Shil Division of AIDS, Center for Immunology and Pathology, National Institute of Health, Seoul, Korea Correspondence to：Joo-Shil Lee, Ph.D. Director, Center for Immunology and Pathology, National Institute of Health 194, Tongillo, Eunpyeong-gu, Seoul 122-701, Korea Tel: +82-2-380-1490, Fax: +82-2-382-6542 E-mail: jooshil@nih.go.kr 032007 19032007 42133 42 20112007 19122007 17012007 Copyright © 2007 Korean Society of Hematology 2007 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Background:

The global effect of HIV infection on the host cell gene expression profiles in healthy HIV-infected patients, as long-term non-progressors, remains largely unknown. To identify the cellular genes related with HIV infection and delayed disease progression in vivo, the host gene expression profiles between healthy HIV-infected Koreans and AIDS patients were investigated.

 Methods:

Differential expression gene analysis was performed via oligonucleotide microarray with using Magic-oligo 10K chip. Ten HIV-uninfected persons and 10 HIV-infected patients (healthy HIV-infected patients vs. AIDS patients. respectively) were studied.

 Results:

Only 10.8% (1,097 genes) of the total genes, that is, 331 up-regulated genes and 766 down-regulated genes were differentially expressed with more than a two-fold change in the HIV-infected persons as compared to those of the HIV-uninfected persons. Especially, 97 genes (8.8%) among 1,097 genes were commonly up- or down-regulated in both the healthy HIV-infected patients and the AIDS patients. 187 genes were differently expressed on the gene expression analysis between the healthy HIV-infected patients and the AIDS patients. Twenty-eight genes out of them showed very significant differences with a P value ＜0.01. Especially, tripartite motif (TRIM) 14 protein and interferon gamma receptor 2 were dramatically up-regulated in healthy HIV-infected patients, while death-associated protein, DNA directed RNA polymerase II polypeptide A and STAT were overexpressed in AIDS patients.

 Conclusion:

Although this microarray study has some limitations, the above results will be helpful for performing more detailed, future functional studies on the differentially expressed genes related to HIV infection and delayed disease progression in vivo.

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Distribution of the changes of gene expression profiles in healthy HIV-infected and AIDS patients compared to those of HIV-uninfected persons. The upper and lower show whole gene expression profiles and the distribution of differentially expressed genes (DEGs) with＞two-fold change between healthy HIV-infected and AIDS patients, respectively. A and H represent AIDS patients and Healthy HIV-in-fected persons. (A and H) means DEGs that were commonly expressed in two groups and (A or H) means the total number of differentially expressed genes with＞two fold change in two groups. Each value of fold change was presented in log 2.

The functional distribution of differentially expressed genes in HIV-infected patients. DEGs were divided into 7 categories based on their function. Numbers mean the percentages of genes in each category compared to total number of genes regulated. (A) The distribution of 331 up-regulated genes based on their cellular function. Genes that involved in signaling/communication were mostly up-regulated. (B) The distribution of overexpressed signaling/communication related genes in HIV-infected patients according to sub-categories. Signaling/communication genes were further divided into 10 classes. Receptors, ligands, and kinases genes were mostly up-regulated. (C) The distribution of 766 down-regulated genes based on their cellular function. (D) Distribution of down-regulated signaling/communication related genes in HIV-infected patients according to sub-categories. Signaling/communication genes were further divided into 10 classes. Receptors related genes were mostly down-regulated.

The representative genes that were commonly up-regulated in Healthy HIV-infected and AIDS groups compared to those of HIV-uninfected group

Functional group Gene symbol Gene description ACC. No Fold change
Gene/protein expression ZDHHC2 Zinc finger, DHHC domain containing 2 NM_016353.1 1.07
  KIAA0741 Translation initiation factor IF2 AB018284.1 1.25
Immune response IFIT4 Interferon-induced protein with tetratricopeptide repeats 4 NM_001549.1 1.56
  SSA2 RO/SSA autoantigen NM_004600.1 1.22
Signaling/communication EGR4 Early growth response 4 NM_001965.1 2.08
  STK4 Serine/threonine kinase 4 NM_006282.1 1.53
  PRKG2 Protein kinase, cGMP-dependent, type ii NM_006259.1 1.26
  TTK TTK protein kinase NM_003318.1 1.10
  BKS Brk kinase substrate AJ245719.1 1.04
  PCDH13 Protocadherin 13 AF169693.1 1.41
Structure/mobility SNX7 Sorting nexin 7 AF121857.1 1.63
  TMEPAI Transmembrane, prostate androgen induced RNA NM_020182.1 1.05
  KRT9 Keratin 9 NM_000226.1 1.99
  HIP1 Huntingtin interacting protein 1 NM_005338.1 1.54
　 KNSL5 Kinesin-like 5 NM_004856.1 1.06

The representative genes that were simultaneously down-regulated in Healthy HIV-infected and AIDS groups compared to those of HIV-uninfected group

Functional group Gene symbol Gene description ACC. No Fold change
Gene/protein expression EIF4G1 Eukaryotic translation initiation factor 4 gamma, 1 NM_004953.1 －2.12
RENT1 Regulator of nonsense transcripts 1 NM_002911.1 －1.74
ZFS5 Zinc-finger protein D70835.1 －1.72
PRPF8 U5 snRNP-specific protein NM_006445.1 －1.61
EEF1A1 Eukaryotic translation elongation factor 1 alpha 1 NM_001402.1 －1.56
Immune response FCER1A Fc fragment of IgE, high affinity i, receptor for; alpha polypeptide NM_002001.1 －2.65
C1QR1 Complement component c1q receptor NM_012072.1 －2.51
TACTILE T cell activation, increased late expressio n NM_005816.1 －2.11
CXCL16 Chemokine (c-x-c motif) ligand 16 NM_022059.1 －1.70
PPBP Pro-platelet basic protein NM_002704.1 －1.53
Oncogene GAS41 Glioma-amplified sequence-41 NM_006530.1 －2.43
MYC V-myc myelocytomatosis viral oncogene homolog (avian) NM_002467.1 －2.32
MYCL2 V-myc myelocytomatosis viral oncogene homolog 2 (avian) NM_005377.1 －1.99
GCYS20 Gastric cancer-related protein gcys-20 AF219140.1 －1.87
TRAF5 TNF receptor-associated factor 5 NM_004619.1 －1.55
Cell division REC14 Meiotic recombination protein AF309553.1 －1.65
Signaling/communication KCND3 Potassium voltage-gated channel, shal-related subfamily, member 3 NM_004980.1 －5.61
PRKDC Protein kinase, DNA-activated, catalytic polypeptide NM_006904.1 －2.16
GABRB3 Gamma-aminobutyric acid (gaba) a receptor, beta 3, isoform1 precursor NM_000814.1 －2.08
FGFR2 Fibroblast growth factor receptor 2, isoform 3 precursor NM_022970.1 －1.89
GPR64 G protein-coupled receptor 64 XM_013056.1 －1.83
EBI2 EBV-induced g protein-coupled receptor 2 2 NM_004951.1 －1.61
Structure/mobility TNNT1 Troponin t1, skeletal, slow XM_048167.1 －2.90
  CLC Charot-leyden crystal protein NM_001828.1 －2.30

Gene lists showing the significant difference with P＜0.01 in gene expression profiles between healthy HIV-infected and AIDS patients by the univariate test

Gene Gene description Fold change∗ ACC. No
LOC51174 Delta-tubulin 0.042 NM 016261.1
RBPJK Recombination signal binding protein 0.067 L07875.1
TRIM14 Tripartite motif protein trim14 isoform alpha; trim14 0.079 NM_033220
IFNGR2 Interferon gamma receptor 2 (interferon gamma transducer 1) 0.093 NM_005534.1
C18ORF1 Chromosome 18 open reading frame 1 0.099 NM_004338.1
  Potassium large conductance calcium-activated channel 0.105 NM_014407.1
CNTN3 Contactin 3 (plasmacytoma associated) 0.128 XM_039627.1
MAP-1 Map-1 protein 0.314 NM_022151.1
  Complement c1r-like proteinase precursor loc51279 0.438 XM_043329.1
  cAMP response element-binding protein cre-bpa 0.442 NM_004904.1
PRX2 Paired related homeobox protein 2.121 NM_016307.1
FZD10 Frizzled homolog 10 (drosophila) 2.212 NM_007197.1
TRIP11 Thyroid hormone receptor interactor 11 2.223 NM_004239.1
STAT2 Signal transducer and activator of transcription 2 2.312 NM_005419.1
SNAPC2 Small nuclear RNA activating complex, polypeptide 2 2.348 NM_003083.1
AFAP Actin filament associated protein 2.581 XM_052622.1
IFNA6 Interferon, alpha 6 3.495 NM_021002.1
ZNFL69 Krueppel-type zinc finger protein 3.644 U28251.1
ARPC4 Actin related protein 2/3 complex, subunit 4 4.565 NM_005718.1
DAPK3 Death-associated protein kinase 3 5.174 XM_031906.1
DMRT1 Doublesex and mab-3 related transcription factor 1 8.164 NM_021951.1
POLR2A DNA directed RNA polymerase ii polypeptide A 11.344 NM_000937.1
  Mip-t3 14.744 AF230877.1
H2BFH H2b histone family, member h 20.468 NM_003523.1
MEF2A Mads box transcription enhancer factor 2 29.941 NM_005587.1
KIAA0925 Kiaa0925 protein 37.106 AB023142.1

∗Fold change means the fold difference of geometric mean values in AIDS patients versus Healthy HIV-infected patients