Lassa virus detection using gene expression analysis
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This document describes a study that used gene expression analysis to identify genes that are differentially expressed during Lassa virus infection. Researchers took blood samples from infected non-human primates before infection and 3 days post-infection. They used microarrays to compare gene expression between the two time points. Many interferon-induced genes were found to be upregulated at 3 days post-infection, indicating an antiviral response. Some genes also showed Lassa-specific expression patterns. The researchers aim to validate these findings experimentally to better understand Lassa virus pathogenesis and diagnosis.
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Lassa virus detection using gene expression analysis
- 1. Detection Using Gene Expression Analysis Nacho Caballero Gracia Bonilla Jaeyoon Chung MEEDIACVKDLVSKYLVDNERLSRQKLAFLVQTEPRMLLMEGLKLLSLCIEVDSCNANGCEHNSEDKSVERILHDHGILTPSLCLWYPDGYK LTGNVLILLECFVRSSPANFEQKYIEDFKKLEQLKEDLKSVDINLIPLIDGRTSFYNEQIPDWVNDKLRDTLFSLLKYAQESNSLFEESEYS RLCESLFMTSGRLSGVESLNVLMDNRSNHYEEVIASCHQGINNKLTAHEVKLQIEEEYQVFRNRLRKGEIEGQFLKVDKSQLLNELNNLYAD KVVAEDNIEHLIYQFKRASPILRFLYANVDEGNEKRGNQTIGECQVQCWRSFLNKVKSLRILNTRRKLLLIFDALILLASKHDLMKQKCLKG WLGSCFLRVKDRLVSLEATKRDLEKWGERGNRLRSRITQSSQCLSKNQILNSIFQKTILKATTALKDVGISVDHYKIDMEVICLNSYDLIMD FDVSGVVPTISYQRTEEETFPYVMGDVELLGTTDLERLSSLSLALVNSMKTSSTVKLRQNEFGPARYQVVRCKEAYCQEFSLGNTELQLIYQ KTGECSKCYAINDNKVGEVCSFYADPKRYFPAIFSAEVLQTTISTMISWIEDCNELEGQLNNIRSLTKMILVLILAHPSKRSQKLLQNLRYF VMAYLSDYHHKDLIDKIREELITDVEFLLYRLIRTLMNLVLSEDVKSMMTNRFKFILNVSYMCHFITKETPDRLTDQIKCFEKFLEPKVRFG HVSTNPADTATEEELDDMVYNAKKFLSKDGCTTIEGPDYKRPGVSKKYLSLLTSSFNNGSLFKEREVKREIKDPLITSGSAALDLASKKSVV VNKYTDGSRILNYDFNKLTALAVSQLTEVFSRKGKYLLNKQDYEYKVQQAMSNLVLGSGQLKSDADGADLDEILLDGGASDYFDQLKETVEK IVDQYREPVKLGSGPNGDGQPSINDLDEIVSNKFYIRLIKGELSNHMVEEFDHDILPGKFYEEFCNAVYENSRLKQKYFYCGHMSQCPIGEL TKAVSTRTYFNHEYFQCFKSILLIMNANTLMGRYTHYKSRNLNFKFDMGKLSDDVRISERESNSEALSKALSLTNCTTAMLKNLCFYSQESP QSYDSVGPDTGRLKFSLSYKEQVGGNRELYIGDLRTKMFTRLIEDYFEAISLQLSGSCLNNEKEFENAILSMKLNVSLAHVSYSMDHSKWGP MMCPFLFLTVLQNLIFLSKDLQADIKGRDYLSTLLMWHMHKMVEIPFNVVTAMMKSFIKAQLGLRKKTKQSITEDFFYSNFQAGVVPSHISS ILDMGQGILHNTSDFYALISERFINYAISCICGGTIDAYTSSDDQISLFDQSLTELLQRDPEEFRTLIEFHYYMSDQLNKFVSPKSVIGRFV AEFKSRFFVWGDEVPLLTKFVAAALHNIKCKEPHQLAETIDTIIDQSVANGVPVHLCNLIQKRTLNPLQYARYPIDPFLLNCETDVRDWVDG NRSYRIMRQIEGLIPNACSKIRSMLRKLYNRLKTGQLHEEFTTNYLSSEHLSSLRNLCELLDVEPPSESDLEYSWLNLAAHHPLRMVLRQKI IYSGAVNLDDEKIPTIVKTIQNKLSSTFTRGAQKLLSEAINKSAFQSSIASGFVGLCRTLGSKCVRGPNKENLYIKSIQSLISDVKGIKLLT NSNGIQYWQVPLELRNGSGGESVVSYFRPLLWDYMCISLSTAIELGAWVLGEPKTVKVFDFFKHNPCDYFPLKPTASKLLEDRVGLNHIIHS LRRLYPSVFEKHILPFMSDLASTKMKWSPRIKFLDLCVALDVNCEALSLVSHIVKWKREEHYIVLSSELRLSHSRTHEPMVEERVVSTSDAV DNFMRQIYFESYVRPFVATTRTLGSFTWFPHKTSVPEGEGLHRMGPFSSFVEKVIHKGVERPMFKHDLMMGYAWIDFDIEPARFNQNQLIAS GLVDPKFDSLEDFFDAVASLPPGSAKLSQTVRFRVKSQDASFKESFAIHLEYTGSMNQQAKYLVHDVTVMYSGAVSPCVLSDCWRLVLSGPT FKGKSAWYVDTEIINEFLIDTNQLGHVTPVEIVVDMERLQFTEYDFVLVGPCTEPTPLVVHRGGLWECGKKLASFTPVIQDQDLEIFVREVG DTSSDLLIGALSDMMIDRLGLRMQWSGVDIVSTLRAAAPSCEGILSAVLEAVDNWVEFKGYALCYSKSRGKVMVQSSGGKLRLKGRTCEEL MSASKEIKSFLWTQSLRRELSGYCSNIKLQVVKDAQALLHGL DFSEVSNVQRLMRKERRDDNDLKRLRDLNQAVNNLVELKSTQ QKSILRVGTLTSDDLLILAADLEKLKSKVIRTERPLSAGVYM GNLSSQQLDQRRALLNMIGMSGGNQGARAGRDGVVRVWDVKN AELLNNQFGTMPSLTLACLTKQGQVDLNDAVQALTDLGLIYT AKYPNTSDLDRLTQSHPILNMIDTKKSSLNISGYNFSLGAAV KAGACMLDGGNMLETIKVSPQTMDGILKSILKVKKALGMFIS DTPGERNPYENILYKICLSGDGWPYIASRTSITGRAWENTVV DLESDGKPQKADSNNSSKSLQSAGFTAGLTYSQLMTLKDAML QLDPNAKTWMDIEGRPEDPVEIALYQPSSGCYIHFFREPTDL KQFKQDAKYSHGIDVTDLFATQPGLTSAVIDALPRNMVITCQ GSDDIRKLLESQGRKDIKLIDIALSKTDSRKYENAVWDQYKD LCHMHTGVVVEKKKRGGKEEITPHCALMDCIMFDAAVSGGLN TSVLRAVLPRDMVFRTSTPRVVL MGNKQAKAPESKDSPRASLIPDATHLGPQFCKSCWFENKGLVECNNHYL CLNCLTLLLSVSNRCPICKMPLPTKLRPSAAPTAPPTGAADSIRPPPYS AAWTNWDCIMTSYQYLIIQNTTWEDNWDCIMTSYQYLIIQNTTWEDAWE MGQIVTFFQEVPHVIEEVMNIVLIALSVLAVLKGLYNFATCGLVGLVTF LLLCGRSCTTSLYKGVYELQTLELNMETLNMTMPLSCTKNNSHHYIMVG NETGLELTLTNTSIINHKFCNLSDAHKKNLYDHALMSIISTFHLSIPNF NQYEAMSCDFNGGKISVQYNLSHSYAGDAANHCGTVANGVLQTFMRMAW GGSYIALDSGRGNWDCIMTSYQYLIIQNTTWEDHCQFSRPSPIGYLGLL SQRTRDIYISRRLLGTFTWTLSDSEGKDTPGGYCLTRWMLIEAELKCFG NTAVAKCNEKHDEEFCDMLRLFDFNKQAIQRLKAEAQMSIQLINKAVNA LINDQLIMKNHLRDIMGIPYCNYSKYWYLNHTTTGRTSLPKCWLVSNGS YLNETHFSDDIEQQADNMITEMLQKEYMERQGKTPLGLVDLFVFSTSFY LISIFLHLVKIPTHRHIVGKSCPKPHRLNHMGICSCGLYKQPGVPVKWK RNA Polymerase Nucleoprotein Matrix Protein Glycoprotein LassaVirus
- 2. Lassa fever is currently diagnosed at late stages
- 4. 3 days post infection Pre Infection 2-color microarrays
- 5. 3 days post infection Pre Infection We pooled samples by timepoint background corrected and normalized
- 6. Reference Sample Log Ratio = Reference Sample Log Ratio = 3 days post infection Pre Infection Log ratios
- 7. Log Fold Change 3 DPI vs Pre = 3 days post infection Pre Infection Log Fold Change
- 8. Log Fold Change 3 DPI vs Pre = 3 days post infection Pre Infection P-value depends on number of individuals variance of individual log ratios magnitude of log fold change
- 9. 2 Pre 3 DPI vs Pre 6 DPI vs Pre 8 DPI vs Pre 10 DPI vs Pre 12 DPI vs Pre
- 10. Pre 3 DPI vs Pre 6 DPI vs Pre 8 DPI vs Pre 10 DPI vs Pre 12 DPI vs Pre Probes with significant p-values at 3 DPI vs Pre 2
- 11. 2 Pre 3 DPI vs Pre 6 DPI vs Pre 8 DPI vs Pre 10 DPI vs Pre 12 DPI vs Pre Probes with significant p-values at 3 DPI vs Pre and sustained log fold changes
- 14. Combined vs Subtypes Combined white blood cells Helper T cells Killer T cells Macrophages B cells
- 15. Common Response Lassa Marburg Ebola LCMV Flu
- 17. A1BG A2M A2MP1 NAT1 NAT2 AACP SERPINA3 AADAC AAMP AANAT AARS AAV ARG1 ARG2 RHOA RHOB RHOC RND3 RHOG ARHGAP1 ARHGAP4 ARHGAP5 ARHG ARHGDIA ARHGDIB ARHGDIG RHOH ARL1 PHOX2A ARL2 ARL3 ARNT ARNTL ARR ARRB1 ARRB2 ARSA ARSB STS ARSC2 ARSD ARSE ARSF ART1 ART2P ART3 ART4 ARVD3 ARVD4 ASAH1 ASCL1 ASCL2 ASD1 ASGR1 ASGR2 ASIP ASL ASLP1 ASMD ASNA1 ASNS ASNSP2 ASPA ASPH ASS1 ASS1P2 ASS1P4 ASS1P5 ASS1P6 ASS1P8 ASS1P10 ASS1P14 ASTN1 SERPINC1 ZFHX3 ATD ATF1 ATF3 ATF4 ATF4P1 ATHS A ATM RERE ATOH1 ATOX1 ATP1A1 ATP1A2 ATP1A3 ATP12A ATP1A4 ATP1B1 ATP ATP1B3 ATP1B3P1 ATP1B1P1 FXYD2 MKKS CHED1 GDF5 MLRG NCOA3 NRIP1 TA CHAF1B C21orf33 AABT BAS DGCR6 DVL1L1 LZTR1 IGLJ CLTCL1 DGCR14 OGS2 S GTPBP6 HDHD1 AKAP17A PNPLA4 CND ZRSR2 USP11 USP9X RBM10 KDM5C SMC IDDMX MRXS12 DXS435E MGR2 HNRNPDP BZX GUST INDX NAA10 F8A1 UBL4A TMEM187 LAGE3 SLC10A3 TKTL1 KDM5D USP9Y EPX ARID1A HIST3H3 DYSF CO SERF1A HIST1H4I TRRAP PICALM KLRC4 SNN ACOX2 ACOX3 AXIN1 AXIN2 BAP1 CDC7 CDC45 EOMES FZD1 FZD4 FZD6 FZD7 FZD8 FZD9 GABPAP GFI1B HIST1H2A HIST1H2AK HIST1H2AJ HIST1H2AL HIST1H2APS4 HIST1H2AC HIST1H2AB HIST HIST2H2AA3 HIST2H2AC HIST1H2BG HIST1H2BL HIST1H2BN HIST1H2BM HIST1 HIST1H2BE HIST1H2BH HIST1H2BI HIST1H2BC HIST1H2BO HIST2H2BE HIST1H3 HIST1H3D HIST1H3C HIST1H3E HIST1H3I HIST1H3G HIST1H3J HIST1H3H HIST1 HIST1H4A HIST1H4D HIST1H4F HIST1H4K HIST1H4J HIST1H4C HIST1H4H HIST HIST1H4E HIST1H4L HIST1H4G HIST2H4A HYAL3 IFIT1P1 LOH1CR1 LOH19CR1 M NME5 OR1A1 OR1D3P OR1D5 OR1E1 OR1E2 OR1E3 OR1G1 OR1P1 OR3A3 PIP5K1A PIP5K1B PIP4K2B PLA2G6 PLA2G10 SCZD6 SCZD7 SLC25A11 SOX14 SPARCL1 SP SRPX TAGLN2 ULK1 UXT RPS9P1 EEA1 BCAR3 ANXA9 STX7 CMAHP BFSP2 SNHG MEHMO BBOX1 LTBP4 ZNF282 STK24 NR0B2 UTF1 RECK SOAT2 SDPR RASAL1 R Most of our candidate genes are interferon induced Identified an early Lassa-specific pattern of expression Carrying out experimental validation