Systems Biology Analysis of the Antagonizing Effects of HIV-1 Tat Expression in the Brain over Transcriptional Changes Caused by Methamphetamine Sensitization
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Doxycycline Regimen
2.3. Methamphetamine-Induced Sensitization
2.4. Brain Harvest
2.5. Gene Expression Array
2.6. Systems Approach
2.7. RT-PCR
2.8. Statistical Analyses
3. Results
3.1. General Findings
3.2. The Effects of Meth-Induced Sensitization: The Comparison between Tat−/Meth vs. Tat−/Sal Animals
3.3. The Effects of Tat Expression: The Comparison Between Tat+/Sal vs. Tat−/Sal
3.4. The Effects of Tat Expression in the Context of Meth-Induced Sensitization: The Comparison Between Tat−/Meth and Tat+/Meth
3.5. The Effects of Meth-Induced Sensitization in the Context of Tat Expression: The Comparison Between Tat+/Meth versus Tat+/Sal
3.6. Prediction of Transcriptional Signatures
3.7. An Unfastened Analytical Strategy Identifies Overlapping Pathways Significantly Affected by Meth, and by Tat+/Meth, in Anti-Directional Ways
3.8. Validation of Genes of Interest
4. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Description | Number of Genes | % of Genes | Number Downregulated | Number Upregulated |
---|---|---|---|---|
Tat−/Meth vs. Tat−/Sal | 712 | 3.85 | 675 | 37 |
Tat+/Meth vs. Tat+/Sal | 0 | 0 | 0 | 0 |
Tat+/Meth vs. Tat−/Meth | 773 | 4.18 | 44 | 729 |
Tat+/Sal vs. Tat−/Sal | 1 | 0.005 | 1 | 0 |
GeneSymbol | Gene Name | Tat−/Meth vs. Tat−/Sal Fold Change | FDR_BH p Value |
---|---|---|---|
Bard1 | BRCA1 associated RING domain 1 | −50.62054 | 1.49 × 10−12 |
Sall4 | sal-like 4 (Drosophila) | −36.81502 | 1.31 × 10−11 |
Krtap10-10 | keratin associated protein 10-10 | −28.0749 | 9.03 × 10−15 |
Krtap8-2 | keratin associated protein 8-2 | −27.74784 | 5.26 × 10−11 |
Olfr1350 | olfactory receptor 1350 | −26.34379 | 7.71 × 10−8 |
Klk11 | kallikrein related-peptidase 11 | −25.88588 | 6.23 × 10−7 |
Krtap5-5 | keratin associated protein 5-5 | −25.47586 | 3.83 × 10−12 |
Sox13 | SRY-box containing gene 13 | −25.23627 | 6.90 × 10−13 |
Elane | elastase, neutrophil expressed | −23.62923 | 1.70 × 10−13 |
Baiap2l2 | BAI1-associated protein 2-like 2 | −22.7781 | 3.03 × 10−14 |
Obp1a | odorant binding protein Ia | −22.46356 | 7.77 × 10−11 |
C87414 | expressed sequence C87414 | −21.31501 | 4.89 × 10−2 |
Chrna2 | cholinergic receptor, nicotinic, alpha polypeptide 2 (neuronal) | −20.67663 | 7.91 × 10−12 |
Vax2 | ventral anterior homeobox containing gene 2 | −20.52762 | 3.65 × 10−13 |
Myod1 | myogenic differentiation 1 | −19.55757 | 3.01 × 10−6 |
Lman1l | lectin, mannose-binding 1 like | −19.06574 | 8.39 × 10−8 |
Tbx10 | T-box 10 | −19.04252 | 3.88 × 10−7 |
Uimc1 | ubiquitin interaction motif containing 1 | −18.35725 | 1.63 × 10−9 |
Adat1 | adenosine deaminase, tRNA-specific 1 | −17.68073 | 7.22 × 10−11 |
Notum | notum pectinacetylesterase homolog (Drosophila) | −17.47123 | 8.13 × 10−14 |
4Sun5 | Sad1 and UNC84 domain containing 5 | −17.39883 | 5.34 × 10−8 |
H2−Ob | histocompatibility 2, O region beta locus | −16.88096 | 5.41 × 10−14 |
Msx2 | homeobox, msh-like 2 | −16.50882 | 7.78 × 10−7 |
Pgc | progastricsin (pepsinogen C) | −15.78614 | 1.38 × 10−11 |
Slc45a3 | solute carrier family 45, member 3 | −15.57587 | 3.57 × 10−13 |
Aldh3a1 | aldehyde dehydrogenase family 3, subfamily A1 | −15.56452 | 1.23 × 10−13 |
Apobec3 | apolipoprotein B mRNA editing enzyme, catalytic polypeptide 3 | −15.04451 | 2.72 × 10−14 |
Cd79a | CD79A antigen (immunoglobulin-associated alpha) | −14.53746 | 1.52 × 10−6 |
Zglp1 | zinc finger, GATA-like protein 1 | −14.42331 | 1.60 × 10−13 |
Tm4sf5 | transmembrane 4 superfamily member 5 | −14.26034 | 6.67 × 10−11 |
Pom121l2 | POM121 membrane glycoprotein-like 2 (rat) | −14.03769 | 2.06 × 10−11 |
Gng4 | guanine nucleotide binding protein (G protein), gamma 4 | −13.83425 | 6.72 × 10−7 |
Cym | chymosin | −13.65853 | 9.79 × 10−14 |
Tsga10ip | testis specific 10 interacting protein | −13.288 | 1.21 × 10−9 |
Msi1 | Musashi homolog 1(Drosophila) | −13.23837 | 7.31 × 10−11 |
Olfr1243 | olfactory receptor 1243 | −12.73216 | 1.03 × 10−8 |
Atp6v1g3 | ATPase, H+ transporting, lysosomal V1 subunit G3 | −11.99044 | 4.40 × 10−10 |
Casp14 | caspase 14 | −11.97585 | 2.44 × 10−12 |
Tgif2lx1 | TGFB−induced factor homeobox 2-like, X-linked 1 | −11.71554 | 8.92 × 10−8 |
Tmem146 | transmembrane protein 146 | −11.54644 | 1.41 × 10−10 |
Gene Symbol | Gene Name | Tat−/Meth vs. Tat−/Sal Fold Change | Tat−/Meth vs. Tat−/Sal FDR BH p Value |
---|---|---|---|
Gm9456 | predicted gene 9456 | 2.001916 | 0.000107467 |
LOC100039183 | serine/threonine-protein kinase MARK2-like | 2.003197 | 2.90 × 10−8 |
Gm1574 | predicted gene 1574 | 2.035995 | 0.002292041 |
Zfp395 | zinc finger protein 395 | 2.036129 | 0.001748075 |
1700110I01Rik | RIKEN cDNA 1700110I01 gene | 2.036459 | 1.13 × 10−6 |
Rarres1 | retinoic acid receptor responder (tazarotene induced) 1 | 2.048939 | 0.005048167 |
Fbxl13 | F-box and leucine-rich repeat protein 13 | 2.058912 | 0.001058074 |
Anp32a | acidic (leucine-rich) nuclear phosphoprotein 32 family, member A | 2.075739 | 0.038582564 |
Mt3 | metallothionein 3 | 2.079847 | 2.92 × 10−7 |
Itprip | inositol 1,4,5-triphosphate receptor interacting protein | 2.081287 | 7.17 × 10−5 |
Wnt3 | wingless-related MMTV integration site 3 | 2.088605 | 0.000620551 |
Zfyve1 | zinc finger, FYVE domain containing 1 | 2.093638 | 6.59 × 10−9 |
Fam89a | family with sequence similarity 89, member A | 2.128657 | 6.71 × 10−5 |
Gm6729 | predicted gene 6729 | 2.129533 | 1.17 × 10−7 |
Iqub | IQ motif and ubiquitin domain containing | 2.132557 | 0.000114519 |
Hadha | hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl-Coenzyme A thiolase/enoyl-Coenzyme A hydratase (trifunctional protein), alpha subunit | 2.143009 | 7.35 × 10−9 |
Eppk1 | epiplakin 1 | 2.143974 | 0.001827944 |
2810410L24Rik | RIKEN cDNA 2810410L24 gene | 2.155585 | 3.74 × 10−6 |
Olfr738 | olfactory receptor 738 | 2.164412 | 0.022625224 |
Wdr96 | WD repeat domain 96 | 2.165153 | 0.002248195 |
Akap14 | A kinase (PRKA) anchor protein 14 | 2.168142 | 0.002020088 |
Ngly1 | N-glycanase 1 | 2.181488 | 5.73 × 10−7 |
Arl6ip1 | ADP-ribosylation factor-like 6 interacting protein 1 | 2.190554 | 4.98 × 10−10 |
Htr6 | 5-hydroxytryptamine (serotonin) receptor 6 | 2.206588 | 0.045116169 |
Tmod4 | tropomodulin 4 | 2.216105 | 1.53 × 10−5 |
Atp10a | ATPase, class V, type 10A | 2.286466 | 0.002265009 |
3000002C10Rik | glyceraldehyde-3-phosphate dehydrogenase pseudogene | 2.32011 | 4.51 × 10−10 |
Fbxo33 | F-box protein 33 | 2.339012 | 6.53 × 10−9 |
Rasd1 | RAS, dexamethasone-induced 1 | 2.364438 | 0.005352506 |
5430417L22Rik | RIKEN cDNA 5430417L22 gene | 2.370661 | 1.40 × 10−5 |
Rfx7 | regulatory factor X, 7 | 2.396731 | 0.000533103 |
Renbp | renin binding protein | 2.400166 | 0.010819928 |
A4galt | alpha 1,4-galactosyltransferase | 2.620867 | 0.000456334 |
Hist4h4 | histone cluster 4, H4 | 3.15377 | 8.77 × 10−11 |
Tmprss11bnl | transmembrane protease, serine 11b N terminal like | 3.158875 | 5.79 × 10−8 |
1700027A23Rik | RIKEN cDNA 1700027A23 gene | 3.438965 | 8.85 × 10−9 |
Gm10461 | predicted gene 10461 | 4.734624 | 2.28 × 10−10 |
Gene Symbol | Gene Name | Tat+/Sal vs. Tat−/Sal Fold Change | FDR BH p Value |
---|---|---|---|
Cox7B | cytochrome c oxidase, subunit XVII assembly protein homolog | −2.327017 | 0.023942447 |
Cbx7 | chromobox homolog 7 | −1.947657 | 0.023942447 |
Lingo1 | leucine rich repeat and Ig domain containing 1 | −1.916766 | 0.02866605 |
1700071K01Rik | RIKEN cDNA 1700071K01 gene | −1.760823 | 0.02866605 |
Gm9372 | predicted gene 9372 | −1.723841 | 0.02866605 |
D230035N22Rik | RIKEN cDNA D230035N22 gene | −1.696028 | 0.023942447 |
Slco1a5 | solute carrier organic anion transporter family, member 1a5 | −1.68099 | 0.035075396 |
Gm17753 | predicted gene, 17753 | −1.679336 | 0.031019153 |
Gm3146 | predicted gene 3146 | −1.535604 | 0.023942447 |
Mpp3 | membrane protein, palmitoylated 3 (MAGUK p55 subfamily member 3) | −1.520024 | 0.03363897 |
Sgcg | sarcoglycan, gamma (dystrophin-associated glycoprotein) | −1.511241 | 0.034422557 |
Bcam | basal cell adhesion molecule | 1.587535 | 0.036223264 |
Matrix | Factor Name | Sequence | Sites Tat−/Meth vs. Tat−/Sal (MSS) | Sites/Sequences Tat−/Meth vs. Tat−/Sal (CSS) | Sites Tat+/Meth vs. Tat−/Meth (MSS) | Sites/Sequences Tat+/Meth vs. Tat−/Meth (CSS) |
---|---|---|---|---|---|---|
V$CPBP_Q6 | KLF6 | | 117 | 5.57 | 1627 | 3.86 |
V$TATA_01 | TBP-related factors | | NS | NS | 156 | 2.82 |
V$BCL6_Q3_01 | BCL-6 factors | | 3 | 3.00 | NS | NS |
V$ZNF333_01 | ZNF333 | | 25 | 2.50 | 369 | 1.84 |
V$MAZ_Q6_01 | MAZ | | 10 | 2.50 | NS | NS |
V$SRY_Q6 | Sox-related factors | | NS | NS | 330 | 1.95 |
V$AP1_03 | AP-1 (JUN/FOS) | | 24 | 2.40 | 198 | 2.28 |
V$ZFP161_04 | ZFP161 | | 21 | 2.33 | NS | NS |
V$SP1_Q6_01 | Sp1 group | | 16 | 2.29 | NS | NS |
V$BEN_01 | BEN | | 29 | 2.23 | NS | NS |
V$NR3C1_03 | GR-like receptors | | 8 | 2.00 | NS | NS |
V$CREBP1_01 | ATF-2 group | | 2 | 2.00 | 145 | 2.07 |
V$P53_04 | TP53 | | 4 | 2.00 | 128 | 1.97 |
V$MYOGENIN_Q6_01 | MYOD1 | | 14 | 2.00 | 398 | 2.57 |
V$BBX_03 | Bbx | | NS | NS | 11 | 1.83 |
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Basova, L.V.; Kesby, J.P.; Kaul, M.; Semenova, S.; Garibaldi Marcondes, M.C. Systems Biology Analysis of the Antagonizing Effects of HIV-1 Tat Expression in the Brain over Transcriptional Changes Caused by Methamphetamine Sensitization. Viruses 2020, 12, 426. https://doi.org/10.3390/v12040426
Basova LV, Kesby JP, Kaul M, Semenova S, Garibaldi Marcondes MC. Systems Biology Analysis of the Antagonizing Effects of HIV-1 Tat Expression in the Brain over Transcriptional Changes Caused by Methamphetamine Sensitization. Viruses. 2020; 12(4):426. https://doi.org/10.3390/v12040426
Chicago/Turabian StyleBasova, Liana V., James P. Kesby, Marcus Kaul, Svetlana Semenova, and Maria Cecilia Garibaldi Marcondes. 2020. "Systems Biology Analysis of the Antagonizing Effects of HIV-1 Tat Expression in the Brain over Transcriptional Changes Caused by Methamphetamine Sensitization" Viruses 12, no. 4: 426. https://doi.org/10.3390/v12040426
APA StyleBasova, L. V., Kesby, J. P., Kaul, M., Semenova, S., & Garibaldi Marcondes, M. C. (2020). Systems Biology Analysis of the Antagonizing Effects of HIV-1 Tat Expression in the Brain over Transcriptional Changes Caused by Methamphetamine Sensitization. Viruses, 12(4), 426. https://doi.org/10.3390/v12040426