title: Transcriptome sequencing of gene expression in the brain of the HIV-1 transgenic rat.
abstract: The noninfectious HIV-1 transgenic (HIV-1Tg) rat was developed as a model of AIDs-related pathology and immune dysfunction by manipulation of a noninfectious HIV-1(gag-pol) virus with a deleted 3-kb SphI-MscI fragment containing the 3' -region of gag and the 5' region of pol into F344 rats. Our previous studies revealed significant behavioral differences between HIV-1Tg and F344 control rats in their performance in the Morris water maze and responses to psychostimulants. However, the molecular mechanisms underlying these behavioral differences remain largely unknown. The primary goal of this study was to identify differentially expressed genes and enriched pathways affected by the gag-pol-deleted HIV-1 genome. Using RNA deep sequencing, we sequenced RNA transcripts in the prefrontal cortex, hippocampus, and striatum of HIV-1Tg and F344 rats. A total of 72 RNA samples were analyzed (i.e., 12 animals per group × 2 strains × 3 brain regions). Following deep-sequencing analysis of 50-bp paired-end reads of RNA-Seq, we used Bowtie/Tophat/Cufflinks suites to align these reads into transcripts based on the Rn4 rat reference genome and to measure the relative abundance of each transcript. Statistical analyses on each brain region in the two strains revealed that immune response- and neurotransmission-related pathways were altered in the HIV-1Tg rats, with brain region differences. Other neuronal survival-related pathways, including those encoding myelin proteins, growth factors, and translation regulators, were altered in the HIV-1Tg rats in a brain region-dependent manner. This study is the first deep-sequencing analysis of RNA transcripts associated the HIV-1Tg rat. Considering the functions of the pathways and brain regions examined in this study, our findings of abnormal gene expression patterns in HIV-1Tg rats suggest mechanisms underlying the deficits in learning and memory and vulnerability to drug addiction and other psychiatric disorders observed in HIV-positive patients.
authors.affiliation: Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, Virginia, United States of America. ml2km@virginia.edu
authors.forename: Ming D
authors.initials: MD
authors.lastname: Li
authors.forename: Junran
authors.initials: J
authors.lastname: Cao
authors.forename: Shaolin
authors.initials: S
authors.lastname: Wang
authors.forename: Ju
authors.initials: J
authors.lastname: Wang
authors.forename: Sraboni
authors.initials: S
authors.lastname: Sarkar
authors.forename: Michael
authors.initials: M
authors.lastname: Vigorito
authors.forename: Jennie Z
authors.initials: JZ
authors.lastname: Ma
authors.forename: Sulie L
authors.initials: SL
authors.lastname: Chang
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D015497:HIV-1 / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D058977:Molecular Sequence Annotation; D051381:Rats; D055647:Rats, Transgenic; D015203:Reproducibility of Results; D015398:Signal Transduction; D014158:Transcription, Genetic; D059467:Transcriptome
references.citation: J Neuroinflammation. 2012 Jan 04;9:3
references.pmid: 22216977
references.citation: PLoS Biol. 2006 Apr;4(4):e115
references.pmid: 16602827
references.citation: PLoS Pathog. 2011 Sep;7(9):e1002213
references.pmid: 21909266
references.citation: Dev Biol. 2009 May 1;329(1):44-54
references.pmid: 19232523
references.citation: Curr Pharm Des. 2005;11(14):1805-43
references.pmid: 15892677
references.citation: Trends Neurosci. 1993 Apr;16(4):131-7
references.pmid: 7682344
references.citation: Am J Hum Genet. 2005 May;76(5):859-64
references.pmid: 15759211
references.citation: Psychiatr Genet. 2002 Mar;12(1):17-22
references.pmid: 11901355
references.citation: Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9380-5
references.pmid: 12089333
references.citation: Bioinformatics. 2012 Aug 15;28(16):2184-5
references.pmid: 22743226
references.citation: Pharmacol Biochem Behav. 2012 Aug;102(2):224-32
references.pmid: 22579910
references.citation: J Neurochem. 2002 Nov;83(4):955-63
references.pmid: 12421368
references.citation: Cancer Res. 2004 Aug 1;64(15):5245-50
references.pmid: 15289330
references.citation: J Neurosci. 2011 Mar 9;31(10):3729-42
references.pmid: 21389228
references.citation: J Allergy Clin Immunol. 2003 Feb;111(2 Suppl):S582-92
references.pmid: 12592304
references.citation: J Neurosci Res. 2002 Jun 15;68(6):647-54
references.pmid: 12111826
references.citation: Mol Immunol. 2004 Aug;41(10):979-84
references.pmid: 15302160
references.citation: Anal Biochem. 1999 May 15;270(1):41-9
references.pmid: 10328763
references.citation: J Neurosci. 1993 May;13(5):2237-48
references.pmid: 8478697
references.citation: J Med Primatol. 2003 Aug;32(4-5):229-39
references.pmid: 14498983
references.citation: Int Rev Neurobiol. 2007;79:203-26
references.pmid: 17531843
references.citation: Alcohol Clin Exp Res. 2013 Jan;37 Suppl 1:E70-8
references.pmid: 22823339
references.citation: Virology. 2006 Feb 20;345(2):373-89
references.pmid: 16289656
references.citation: Nat Biotechnol. 2010 May;28(5):511-5
references.pmid: 20436464
references.citation: Intensive Crit Care Nurs. 2001 Jun;17(3):155-66
references.pmid: 11868686
references.citation: Int J Clin Exp Med. 2012;5(2):105-23
references.pmid: 22567172
references.citation: Mol Psychiatry. 2000 Sep;5(5):495-501
references.pmid: 11032382
references.citation: Mol Psychiatry. 2010 Mar;15(3):272-85, 228
references.pmid: 19621015
references.citation: Cell. 2012 Jun 22;149(7):1549-64
references.pmid: 22726441
references.citation: Eur J Immunol. 2011 Dec;41(12):3412-8
references.pmid: 22076814
references.citation: Eur J Neurosci. 2004 Jun;19(12):3171-82
references.pmid: 15217373
references.citation: Toxicol Sci. 2012 Jan;125(1):209-18
references.pmid: 21976372
references.citation: Invest Ophthalmol Vis Sci. 2012 Jun 26;53(7):3973-89
references.pmid: 22531700
references.citation: Pharmacol Biochem Behav. 2011 Jun;98(4):587-97
references.pmid: 21420997
references.citation: J Biol Chem. 2004 Jun 18;279(25):26748-53
references.pmid: 15084582
references.citation: Neurobiol Aging. 2010 Feb;31(2):224-43
references.pmid: 18479783
references.citation: Amino Acids. 2012 Sep;43(3):1157-69
references.pmid: 22187147
references.citation: J Neurosci Res. 2000 Aug 1;61(3):273-87
references.pmid: 10900074
references.citation: Annu Rev Neurosci. 2002;25:563-93
references.pmid: 12052921
references.citation: Neurobiol Aging. 2011 Dec;32(12):2316.e1-15
references.pmid: 20409609
references.citation: PLoS One. 2009 Sep 18;4(9):e7055
references.pmid: 19763258
references.citation: Neuropsychopharmacology. 2007 May;32(5):1109-21
references.pmid: 17063155
references.citation: Prog Brain Res. 2000;126:255-62
references.pmid: 11105651
references.citation: Biochem Soc Trans. 2012 Aug;40(4):721-7
references.pmid: 22817723
references.citation: Brain Behav Immun. 2011 Jul;25(5):1008-16
references.pmid: 21093580
references.citation: J Pediatr. 2006 Mar;148(3):389-91
references.pmid: 16615974
references.citation: J Biol Chem. 1993 Feb 5;268(4):2857-64
references.pmid: 8428960
references.citation: Kidney Int. 2003 Jun;63(6):2242-53
references.pmid: 12753314
references.citation: Annu Rev Neurosci. 2008;31:535-61
references.pmid: 18558866
references.citation: Hippocampus. 2003;13(7):826-34
references.pmid: 14620878
references.citation: J Infect Dis. 1998 Oct;178(4):1000-7
references.pmid: 9806027
references.citation: Neuropathol Appl Neurobiol. 1992 Oct;18(5):489-501
references.pmid: 1454139
references.citation: Eur J Neurosci. 2007 May;25(9):2619-28
references.pmid: 17561836
references.citation: Curr Opin Microbiol. 2004 Oct;7(5):555-9
references.pmid: 15499686
references.citation: Proc Natl Acad Sci U S A. 2001 Jul 31;98(16):9271-6
references.pmid: 11481487
references.citation: Proc Natl Acad Sci U S A. 2010 Dec 21;107(51):22308-13
references.pmid: 21135234
references.citation: J Neuroimmunol. 2000 Oct 2;110(1-2):134-9
references.pmid: 11024543
references.citation: Ann Neurol. 1992 Jan;31(1):34-8
references.pmid: 1311910
references.citation: Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):16045-50
references.pmid: 18836069
references.citation: Science. 2008 Nov 21;322(5905):1247-50
references.pmid: 19023080
references.citation: Bull Math Biol. 2005 Nov;67(6):1227-51
references.pmid: 16023709
references.citation: Genes Immun. 2011 Sep;12(6):399-414
references.pmid: 21490621
references.citation: Int J Neuropsychopharmacol. 2011 Mar;14(2):157-74
references.pmid: 20196919
references.citation: Drugs. 1995;49 Suppl 1:25-31; discussion 38-40
references.pmid: 7614899
references.citation: Schizophr Res. 2009 Jun;111(1-3):123-30
references.pmid: 19346103
references.citation: Brain Res Mol Brain Res. 2004 Dec 20;132(2):168-80
references.pmid: 15582156
references.citation: J Neuroimmunol. 2005 Oct;167(1-2):72-80
references.pmid: 16087246
references.citation: Lancet. 1998 Aug 1;352(9125):402-3
references.pmid: 9717951
references.citation: J Neurovirol. 2009 Jan;15(1):14-24
references.pmid: 19085205
references.citation: Mol Cell Biol. 2008 Dec;28(23):7050-65
references.pmid: 18809582
references.citation: Front Psychiatry. 2011 Mar 08;2:5
references.pmid: 21556275
references.citation: J Neurovirol. 2003 Apr;9(2):205-21
references.pmid: 12707851
references.citation: Med Hypotheses. 2002 May;58(5):386-7
references.pmid: 12056874
references.citation: J Neurochem. 2009 Jun;109(5):1400-12
references.pmid: 19476551
references.citation: J Biol Chem. 2003 May 9;278(19):16630-41
references.pmid: 12600985
references.citation: J Neuroimmune Pharmacol. 2007 Dec;2(4):319-28
references.pmid: 18040850
references.citation: Virology. 2004 Mar 30;321(1):111-9
references.pmid: 15033570
references.citation: Nihon Rinsho. 1997 Apr;55(4):897-903
references.pmid: 9103891
references.citation: Neurosci Lett. 2001 Jun 1;305(1):5-8
references.pmid: 11356294
references.citation: Cereb Cortex. 2012 Nov;22(11):2486-94
references.pmid: 22120417
references.citation: Hum Genet. 2012 Jun;131(6):843-55
references.pmid: 22048727
references.citation: PLoS One. 2011;6(9):e25406
references.pmid: 21966521
references.citation: Mol Immunol. 2005 Feb;42(2):195-212
references.pmid: 15488608
references.citation: J Neuroimmune Pharmacol. 2006 Jun;1(2):138-51
references.pmid: 18040780
references.citation: J Neuroinflammation. 2011 Aug 16;8:101
references.pmid: 21846384
references.citation: Int J Neuropsychopharmacol. 2011 Feb;14(1):91-106
references.pmid: 20426880
references.citation: Neuropsychopharmacology. 2007 Jan;32(1):110-6
references.pmid: 16794563
references.citation: PLoS One. 2012;7(1):e29868
references.pmid: 22279551
references.citation: Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13500-7
references.pmid: 8942963
references.citation: Br Med Bull. 2001;58:43-59
references.pmid: 11714623
references.citation: Virology. 2006 Mar 15;346(2):460-8
references.pmid: 16375941
references.citation: Am J Pathol. 2004 Sep;165(3):815-24
references.pmid: 15331406
references.citation: J Neuroimmunol. 2012 Jun 15;247(1-2):16-24
references.pmid: 22503372
references.citation: New Microbiol. 2005 Oct;28(4):281-97
references.pmid: 16386013