{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T08:25:37Z","timestamp":1779179137641,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1008307","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2020,2,28]],"date-time":"2020-02-28T00:00:00Z","timestamp":1582848000000}}],"reference-count":83,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2020,2,18]],"date-time":"2020-02-18T00:00:00Z","timestamp":1581984000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["158250"],"award-info":[{"award-number":["158250"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["HOP-134065"],"award-info":[{"award-number":["HOP-134065"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY025536"],"award-info":[{"award-number":["EY025536"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarship"],"award-info":[{"award-number":["Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarship"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013873","name":"Government of Ontario","doi-asserted-by":"publisher","award":["Ontario Graduate Scholarship"],"award-info":[{"award-number":["Ontario Graduate Scholarship"]}],"id":[{"id":"10.13039\/100013873","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"DOI":"10.1371\/journal.ppat.1008307","type":"journal-article","created":{"date-parts":[[2020,2,18]],"date-time":"2020-02-18T13:41:47Z","timestamp":1582033307000},"page":"e1008307","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["An activator of G protein-coupled receptor and MEK1\/2-ERK1\/2 signaling inhibits HIV-1 replication by altering viral RNA processing"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9699-5062","authenticated-orcid":true,"given":"Raymond W.","family":"Wong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahalya","family":"Balachandran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6520-7852","authenticated-orcid":true,"given":"Peter K.","family":"Cheung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5556-8531","authenticated-orcid":true,"given":"Ran","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qun","family":"Pan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1108-7271","authenticated-orcid":true,"given":"Peter","family":"Stoilov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P. Richard","family":"Harrigan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin J.","family":"Blencowe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8974-2451","authenticated-orcid":true,"given":"Donald R.","family":"Branch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan","family":"Cochrane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2020,2,18]]},"reference":[{"key":"ppat.1008307.ref001","unstructured":"Fact sheet\u2014Latest statistics on the status of the AIDS epidemic. In: UNAIDS [Internet]. 2018. Available: http:\/\/www.unaids.org\/en\/resources\/fact-sheet"},{"key":"ppat.1008307.ref002","first-page":"05","article-title":"Trial, Error, and Breakthrough: A Review of HIV Vaccine Development","author":"S M Barry","year":"2014","journal-title":"J AIDS Clin Res"},{"key":"ppat.1008307.ref003","first-page":"a007161","article-title":"HIV-1 Antiretroviral Drug Therapy","volume":"2","author":"EJ Arts","year":"2012","journal-title":"Cold Spring Harb Perspect Me"},{"key":"ppat.1008307.ref004","first-page":"1","article-title":"HIV Entry Inhibitors and Their Potential in HIV Therapy","volume":"1","author":"K Qian","year":"2008","journal-title":"Med Res Rev"},{"key":"ppat.1008307.ref005","doi-asserted-by":"crossref","DOI":"10.1098\/rspb.2017.0525","article-title":"Early antiretroviral therapy and potent second-line drugs could decrease HIV incidence of drug resistance","volume":"284","author":"M Shen","year":"2017","journal-title":"Proc R Soc B Biol Sci"},{"key":"ppat.1008307.ref006","unstructured":"HIV Drug Resistance Report 2017 [Internet]. 2017. Available: http:\/\/apps.who.int\/iris\/handle\/10665\/255896"},{"key":"ppat.1008307.ref007","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1007\/s13181-013-0325-8","article-title":"Review of the Toxicity of HIV Medications","volume":"10","author":"AM Margolis","year":"2014","journal-title":"AJ Med Toxicol"},{"key":"ppat.1008307.ref008","unstructured":"Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV [Internet]. AIDSinfo. 2017. Available: https:\/\/aidsinfo.nih.gov\/guidelines\/html\/1\/adult-and-adolescent-arv\/31\/adverse-effects-of-arv"},{"key":"ppat.1008307.ref009","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0015510","article-title":"Transmitted drug resistance in persons with acute\/early HIV-1 in San Francisco, 2002\u20132009","volume":"5","author":"V Jain","year":"2010","journal-title":"PLoS One"},{"key":"ppat.1008307.ref010","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.bbadis.2009.12.003","article-title":"Host proteins involved in HIV infection: New therapeutic targets","volume":"1802","author":"N Arhel","year":"2010","journal-title":"Biochim Biophys Acta"},{"key":"ppat.1008307.ref011","first-page":"164","article-title":"Clarifying the role of G protein signaling in HIV infection: new approaches to an old question","volume":"12","author":"JA Juno","year":"2010","journal-title":"AIDS Rev"},{"key":"ppat.1008307.ref012","doi-asserted-by":"crossref","first-page":"2550","DOI":"10.1128\/JVI.77.4.2550-2558.2003","article-title":"G Protein-Dependent CCR5 Signaling Is Not Required for Efficient Infection of Primary T Lymphocytes and Macrophages by R5 Human Immunodeficiency Virus Type 1 Isolates","volume":"77","author":"A Amara","year":"2003","journal-title":"J Virol"},{"key":"ppat.1008307.ref013","doi-asserted-by":"crossref","first-page":"7938","DOI":"10.1128\/JVI.79.12.7938-7941.2005","article-title":"G-protein signaling triggered by R5 human immunodeficiency virus type 1 increases virus replication efficiency in primary T lymphocytes","volume":"79","author":"YL Lin","year":"2005","journal-title":"J Virol"},{"key":"ppat.1008307.ref014","doi-asserted-by":"crossref","first-page":"2539","DOI":"10.1128\/JVI.77.4.2539-2549.2003","article-title":"Phosphatidylinositol 3-Kinase Regulates Human Immunodeficiency Virus Type 1 Replication following Viral Entry in Primary CD4+ T Lymphocytes and Macrophages","volume":"77","author":"F Fran\u00e7ois","year":"2003","journal-title":"J Virol"},{"key":"ppat.1008307.ref015","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/j.cell.2008.06.036","article-title":"HIV Envelope-CXCR4 Signaling Activates Cofilin to Overcome Cortical Actin Restriction in Resting CD4 T Cells","volume":"134","author":"A Yoder","year":"2008","journal-title":"Cell"},{"key":"ppat.1008307.ref016","doi-asserted-by":"crossref","first-page":"63","DOI":"10.3390\/v10020063","article-title":"All-Round Manipulation of the Actin Cytoskeleton by HIV","volume":"10","author":"AO Stella","year":"2018","journal-title":"Viruses"},{"key":"ppat.1008307.ref017","doi-asserted-by":"crossref","first-page":"9191","DOI":"10.1128\/JVI.00424-08","article-title":"Induction of the Gq Signaling Cascade by the Human Immunodeficiency Virus Envelope Is Required for Virus Entry","volume":"82","author":"B Harmon","year":"2008","journal-title":"J Virol"},{"key":"ppat.1008307.ref018","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s12977-017-0328-7","article-title":"HIV signaling through CD4 and CCR5 activates Rho family GTPases that are required for optimal infection of primary CD4+ T cells","volume":"14","author":"MB Lucera","year":"2017","journal-title":"Retrovirology"},{"key":"ppat.1008307.ref019","doi-asserted-by":"crossref","first-page":"2558","DOI":"10.1128\/JVI.74.6.2558-2566.2000","article-title":"Inhibition of CD3\/CD28-Mediated Activation of the MEK\/ERK Signaling Pathway Represses Replication of X4 but Not R5 Human Immunodeficiency Virus Type 1 in Peripheral Blood CD4+ T Lymphocytes","volume":"74","author":"Waldemar Popik","year":"2000","journal-title":"J Virol"},{"key":"ppat.1008307.ref020","doi-asserted-by":"crossref","first-page":"485","DOI":"10.3390\/ph4030485","article-title":"Neuropeptide receptors: Novel targets for HIV\/AIDS therapeutics","volume":"4","author":"DR Branch","year":"2011","journal-title":"Pharmaceuticals"},{"key":"ppat.1008307.ref021","doi-asserted-by":"crossref","first-page":"3460","DOI":"10.1128\/JVI.73.4.3460-3466.1999","article-title":"Regulation of human immunodeficiency virus type 1 infectivity by the ERK mitogen-activated protein kinase signaling pathway","volume":"73","author":"X Yang","year":"1999","journal-title":"J Virol"},{"key":"ppat.1008307.ref022","doi-asserted-by":"crossref","first-page":"29879","DOI":"10.1074\/jbc.273.45.29879","article-title":"Mitogen-activated Protein Kinase Phosphorylates and Regulates the HIV-1 Vif Protein Mitogen-activated Protein Kinase Phosphorylates and Regulates the HIV-1 Vif Protein","volume":"273","author":"X Yang","year":"1998","journal-title":"J Biol Chem"},{"key":"ppat.1008307.ref023","doi-asserted-by":"crossref","first-page":"4038","DOI":"10.1096\/fj.06-7325com","article-title":"CCR5 signaling through phospholipase D involves p44\/42 MAP-kinases and promotes HIV-1 LTR-directed gene expression","volume":"21","author":"S Paruch","year":"2007","journal-title":"FASEB J"},{"key":"ppat.1008307.ref024","first-page":"470","article-title":"SDF-1-induced activation of ERK enhances HIV-1 expression","volume":"11","author":"M Montes","year":"2000","journal-title":"Eur Cytokine Netw"},{"key":"ppat.1008307.ref025","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1097\/01.aids.0000171403.07995.92","article-title":"Soluble HIV-1 gp120 enhances HIV-1 replication in non-dividing CD4+ T cells, mediated via cell signaling and Tat cofactor overexpression","volume":"19","author":"D Miss\u00e9","year":"2005","journal-title":"AIDS"},{"key":"ppat.1008307.ref026","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1099\/vir.0.064618-0","article-title":"The PI3K pathway acting on alternative HIV-1 pre-mRNA splicing","volume":"95","author":"F Hillebrand","year":"2014","journal-title":"J Gen Virol"},{"key":"ppat.1008307.ref027","doi-asserted-by":"crossref","first-page":"e1003241","DOI":"10.1371\/journal.ppat.1003241","article-title":"Digoxin Suppresses HIV-1 Replication by Altering Viral RNA Processing","volume":"9","author":"RW Wong","year":"2013","journal-title":"PLoS Pathog. PLOS Pathogens"},{"key":"ppat.1008307.ref028","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1038\/s41598-018-19298-x","article-title":"Cardiac glycoside\/aglycones inhibit HIV-1 gene expression by a mechanism requiring MEK1\/2-ERK1\/2 signaling","volume":"8","author":"RW Wong","year":"2018","journal-title":"Sci Rep"},{"key":"ppat.1008307.ref029","first-page":"32","article-title":"Cardiotonic steroids on the road to anti-cancer therapy","volume":"1776","author":"T Mijatovic","year":"2007","journal-title":"Biochim Biophys Acta"},{"key":"ppat.1008307.ref030","doi-asserted-by":"crossref","first-page":"2607","DOI":"10.1093\/emboj\/17.9.2607","article-title":"Modulation of HIV-1 infectivity by MAPK, a virion-associated kinase","volume":"17","author":"J-M Jacque","year":"1998","journal-title":"EMBO J"},{"key":"ppat.1008307.ref031","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1099\/vir.0.019604-0","article-title":"Lentivirus-associated MAPK\/ERK2 phosphorylates EMD and regulates infectivity","volume":"91","author":"TN Bukong","year":"2010","journal-title":"J Gen Virol"},{"key":"ppat.1008307.ref032","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/1742-4690-3-82","article-title":"Modification of the Tet-On regulatory system prevents the conditional-live HIV-1 variant from losing doxycycline-control","volume":"3","author":"X Zhou","year":"2006","journal-title":"Retrovirology"},{"key":"ppat.1008307.ref033","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/1742-4690-8-47","article-title":"Differential effect of CLK SR Kinases on HIV-1 gene expression: potential novel targets for therapy","volume":"8","author":"R Wong","year":"2011","journal-title":"Retrovirology"},{"key":"ppat.1008307.ref034","doi-asserted-by":"crossref","first-page":"21083","DOI":"10.1074\/jbc.M110.195537","article-title":"High-throughput Screening Uncovers a Compound That Activates Latent HIV-1 and Acts Cooperatively with a Histone Deacetylase (HDAC) Inhibitor*","volume":"286","author":"S Micheva-Viteva","year":"2011","journal-title":"J Biol Chem"},{"key":"ppat.1008307.ref035","doi-asserted-by":"crossref","first-page":"417","DOI":"10.2217\/17460913.1.4.417","article-title":"Transcriptional and post-transcriptional regulation of HIV-1 gene expression: role of cellular factors for Tat and Rev","volume":"1","author":"S Nekhai","year":"2006","journal-title":"Future Microbiol"},{"key":"ppat.1008307.ref036","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1006\/abbi.1999.1207","article-title":"The ins and outs of HIV Rev","volume":"365","author":"TJ Hope","year":"1999","journal-title":"Arch Biochem Biophys"},{"key":"ppat.1008307.ref037","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1146\/annurev.micro.52.1.491","article-title":"The HIV-1 Rev Protein","volume":"52","author":"VW Pollard","year":"1998","journal-title":"Annu Rev Microbiol"},{"key":"ppat.1008307.ref038","first-page":"103","article-title":"Stable complex formation between HIV Rev and the nucleosome assembly protein, NAP1, affects Rev function","volume":"388","author":"A Cochrane","year":"2009","journal-title":"Virology. Elsevier Inc."},{"key":"ppat.1008307.ref039","doi-asserted-by":"crossref","first-page":"9471","DOI":"10.1093\/nar\/gkt727","article-title":"Characterization of novel inhibitors of HIV-1 replication that function via alteration of viral RNA processing and rev function","volume":"41","author":"RW Wong","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"ppat.1008307.ref040","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s12977-017-0330-0","article-title":"Identification of small molecule modulators of HIV-1 Tat and Rev protein accumulation","volume":"14","author":"A Balachandran","year":"2017","journal-title":"Retrovirology"},{"key":"ppat.1008307.ref041","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s12977-015-0159-3","article-title":"Long lasting control of viral rebound with a new drug ABX464 targeting Rev\u2013mediated viral RNA biogenesis","volume":"12","author":"N Campos","year":"2015","journal-title":"Retrovirology"},{"key":"ppat.1008307.ref042","doi-asserted-by":"crossref","first-page":"4051","DOI":"10.1093\/nar\/gkw1223","article-title":"Modulation of the splicing regulatory function of SRSF10 by a novel compound that impairs HIV-1 replication","volume":"45","author":"L Shkreta","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"ppat.1008307.ref043","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1371\/journal.ppat.0030159","article-title":"Small-molecule inhibition of HIV pre-mRNA splicing as a novel antiretroviral therapy to overcome drug resistance","volume":"3","author":"N Bakkour","year":"2007","journal-title":"PLoS Pathog"},{"key":"ppat.1008307.ref044","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1021\/acs.jmedchem.5b01357","article-title":"A Parallel Synthesis Approach to the Identification of Novel Diheteroarylamide-Based Compounds Blocking HIV Replication: Potential Inhibitors of HIV-1 Pre-mRNA Alternative Splicing","volume":"59","author":"PK Cheung","year":"2016","journal-title":"J Med Chem"},{"key":"ppat.1008307.ref045","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1038\/ng.259","article-title":"Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing","volume":"40","author":"Q Pan","year":"2008","journal-title":"Nat Genet"},{"key":"ppat.1008307.ref046","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/nature07509","article-title":"Alternative isoform regulation in human tissue transcriptomes","volume":"456","author":"ET Wang","year":"2008","journal-title":"Nature"},{"key":"ppat.1008307.ref047","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1038\/nature13319","article-title":"Mass-spectrometry-based draft of the human proteome","volume":"509","author":"M Wilhelm","year":"2014","journal-title":"Nature"},{"key":"ppat.1008307.ref048","doi-asserted-by":"crossref","first-page":"11329","DOI":"10.1073\/pnas.0604616103","article-title":"Utilization of host SR protein kinases and RNA-splicing machinery during viral replication","volume":"103","author":"T Fukuhara","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ppat.1008307.ref049","first-page":"3921","article-title":"Negative and Positive mRNA Splicing Elements Act Competitively To Regulate Human Immunodeficiency Virus Type 1","volume":"82","author":"CM Exline","year":"2008","journal-title":"Vif Gene Expression. J Virol"},{"key":"ppat.1008307.ref050","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1073\/pnas.94.3.973","article-title":"HIV Rev-dependent binding of SF2\/ASF to the Rev response element: possible role in Rev-mediated inhibition of HIV RNA splicing","volume":"94","author":"DM Powell","year":"1997","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ppat.1008307.ref051","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1017\/S1355838201001212","article-title":"The sequence complementarity between HIV-1 5 \u2018 splice site SD4 and U1 snRNA determines the steady-state level of an unstable env pre-mRNA","volume":"7","author":"S Kammler","year":"2001","journal-title":"RNA"},{"key":"ppat.1008307.ref052","doi-asserted-by":"crossref","first-page":"6517","DOI":"10.1128\/JVI.78.12.6517-6526.2004","article-title":"A bidirectional SF2\/ASF- and SRp40-dependent splicing enhancer regulates human immunodeficiency virus type 1 rev, env, vpu, and nef gene expression","volume":"78","author":"M Caputi","year":"2004","journal-title":"J Virol"},{"key":"ppat.1008307.ref053","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1128\/JVI.01801-08","article-title":"Role of cellular RNA processing factors in human immunodeficiency virus type 1 mRNA metabolism, replication, and infectivity","volume":"83","author":"JA Jablonski","year":"2009","journal-title":"J Virol"},{"key":"ppat.1008307.ref054","doi-asserted-by":"crossref","first-page":"29963","DOI":"10.1074\/jbc.M404452200","article-title":"Differential effects of the SR proteins 9G8, SC35, ASF\/SF2, and SRp40 on the utilization of the A1 to A5 splicing sites of HIV-1 RNA","volume":"279","author":"D Ropers","year":"2004","journal-title":"J Biol Chem"},{"key":"ppat.1008307.ref055","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/1742-4690-2-33","article-title":"Dual effect of the SR proteins ASF\/SF2, SC35 and 9G8 on HIV-1 RNA splicing and virion production","volume":"2","author":"S Jacquenet","year":"2005","journal-title":"Retrovirology"},{"key":"ppat.1008307.ref056","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/nmeth.1314","article-title":"SUnSET, a nonradioactive method to monitor protein synthesis","volume":"6","author":"EK Schmidt","year":"2009","journal-title":"Nat Methods"},{"key":"ppat.1008307.ref057","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1074\/mcp.M116.065524","article-title":"Extended Multiplexing of Tandem Mass Tags (TMT) Labeling Reveals Age and High Fat Diet Specific Proteome Changes in Mouse Epididymal Adipose Tissue","volume":"16","author":"DL Plubell","year":"2017","journal-title":"Mol Cell Proteomics"},{"key":"ppat.1008307.ref058","first-page":"26563","article-title":"Activation of the Protein Kinase ERK5\/BMK1 by Receptor","volume":"274","author":"S Kamakura","year":"1999","journal-title":"Biochemistry"},{"key":"ppat.1008307.ref059","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1111\/j.1476-5381.2012.01859.x","article-title":"A guide to picking the most selective kinase inhibitor tool compounds for pharmacological validation of drug targets","volume":"166","author":"JCM Uitdehaag","year":"2012","journal-title":"Br J Pharmacol"},{"key":"ppat.1008307.ref060","doi-asserted-by":"crossref","first-page":"E3785","DOI":"10.1073\/pnas.1406559111","article-title":"Src promotes GTPase activity of Ras via tyrosine 32 phosphorylation","volume":"111","author":"S Bunda","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ppat.1008307.ref061","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1038\/nrg3922","article-title":"Evolutionary consequences of drug resistance: shared principles across diverse targets and organisms","volume":"16","author":"D Hughes","year":"2015","journal-title":"Nat Rev Genet"},{"key":"ppat.1008307.ref062","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0065-3233(01)56002-7","article-title":"Angiotensin-converting enzyme inhibitors","volume":"56","author":"J Menard","year":"2001","journal-title":"Adv Protein Chem"},{"key":"ppat.1008307.ref063","doi-asserted-by":"crossref","first-page":"99","DOI":"10.5694\/j.1326-5377.2003.tb05445.x","article-title":"New drugs, old drugs: Digoxin in heart failure and cardiac arrhythmias","volume":"179","author":"TJ Campbell","year":"2003","journal-title":"Med J Aust"},{"key":"ppat.1008307.ref064","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1002\/jnr.10784","article-title":"Cysteine Proteases Are the Major Beta-Secretase in the Regulated Secretory Pathway That Provides Most of the Beta-Amyloid in Alzheimer\u2019s Disease: Role of BACE 1 in the Constitutive Secretory Pathway","volume":"74","author":"VYH Hook","year":"2003","journal-title":"J Neurosci Res"},{"key":"ppat.1008307.ref065","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1038\/nrm2777","article-title":"Mechanisms of alternative splicing regulation: insights from molecular and genomics approaches","volume":"10","author":"M Chen","year":"2009","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ppat.1008307.ref066","doi-asserted-by":"crossref","first-page":"3663","DOI":"10.1093\/nar\/gkr1238","article-title":"Differential effects of hnRNP D\/AUF1 isoforms on HIV-1 gene expression","volume":"40","author":"N Lund","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"ppat.1008307.ref067","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.1021\/ci400180f","article-title":"Murine mPGES-1 3D structure elucidation and inhibitors binding mode predictions by homology modeling and site-directed mutagenesis","author":"G Corso","year":"2013","journal-title":"Journal of Chemical Information and Modeling"},{"key":"ppat.1008307.ref068","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0125315","article-title":"Differential effects of Tra2\u03b2 isoforms on HIV-1 RNA processing and expression","volume":"10","author":"C Platt","year":"2015","journal-title":"PLoS One"},{"key":"ppat.1008307.ref069","unstructured":"Wong RW. Targeting Viral RNA Processing to Control HIV-1 Infection [Internet]. University of Toronto. 2018. Available: https:\/\/search.library.utoronto.ca\/details?11698325"},{"key":"ppat.1008307.ref070","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.coviro.2016.03.004","article-title":"Current status and prospects of HIV treatment","volume":"18","author":"T Cihlar","year":"2016","journal-title":"Curr Opin Virol"},{"key":"ppat.1008307.ref071","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S1074-5521(97)90257-X","article-title":"Leptomycin B is an inhibitor of nuclear export: inhibition of nucleo-cytoplasmic translocation of the human immunodeficiency virus type 1 (HIV-1) Rev protein and Rev-dependent mRNA","volume":"4","author":"B Wolff","year":"1997","journal-title":"Chem Biol"},{"key":"ppat.1008307.ref072","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1261\/rna.032912.112","article-title":"The cardiotonic steroid digitoxin regulates alternative splicing through depletion of the splicing factors SRSF3 and TRA2B","volume":"18","author":"ES Anderson","year":"2012","journal-title":"RNA"},{"key":"ppat.1008307.ref073","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1128\/MCB.01301-09","article-title":"Rapid-response splicing reporter screens identify differential regulators of constitutive and alternative splicing","volume":"30","author":"I Younis","year":"2010","journal-title":"Mol Cell Biol"},{"key":"ppat.1008307.ref074","first-page":"1","article-title":"A survey of best practices for RNA-seq data analysis","volume":"17","author":"A Conesa","year":"2016","journal-title":"Genome Biol"},{"key":"ppat.1008307.ref075","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1124\/mi.3.3.157","article-title":"Na+-K+\u2014ATPase-mediated signal transduction: from protein interaction to cellular function","volume":"3","author":"Z Xie","year":"2003","journal-title":"Mol Interv"},{"key":"ppat.1008307.ref076","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1177\/1947601911407328","article-title":"The ERK Cascade: Distinct Functions within Various Subcellular Organelles","volume":"2","author":"I Wortzel","year":"2011","journal-title":"Genes Cancer"},{"key":"ppat.1008307.ref077","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s12026-010-8170-1","article-title":"Signaling through the P38 and ERK pathways: a common link between HIV replication and the immune response","volume":"48","author":"RL Furler","year":"2010","journal-title":"Immunol Res"},{"key":"ppat.1008307.ref078","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1152\/physrev.00003.2005","article-title":"Mammalian G Proteins and Their Cell Type Specific Functions","volume":"85","author":"N Wettschureck","year":"2005","journal-title":"Physilological Rev"},{"key":"ppat.1008307.ref079","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1097\/QAI.0000000000002144","article-title":"Targeting ABL1 or ARG Tyrosine Kinases to Restrict HIV-1 Infection in Primary CD4+ T-Cells or in Humanized NSG Mice","volume":"82","author":"SDS McCarthy","year":"2019","journal-title":"J Acquir Immune Defic Syndr"},{"key":"ppat.1008307.ref080","doi-asserted-by":"crossref","first-page":"4060","DOI":"10.1111\/bph.14157","article-title":"The current state of GPCR-based drug discovery to treat metabolic disease","volume":"175","author":"KW Sloop","year":"2018","journal-title":"Br J Pharmacol"},{"key":"ppat.1008307.ref081","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1093\/cvr\/cvv216","article-title":"Endothelial Gaq\/11 is required for VEGF-induced vascular permeability and angiogenesis","volume":"108","author":"KK Sivaraj","year":"2015","journal-title":"Cardiovasc Res"},{"key":"ppat.1008307.ref082","first-page":"499","article-title":"mRNA and protein expression of selective alpha subunits of G proteins are abnormal in prefrontal cortex of suicide victims","volume":"27","author":"Y Dwivedi","year":"2002","journal-title":"Neuropsychopharmacology"},{"key":"ppat.1008307.ref083","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1016\/j.cell.2014.11.035","article-title":"A highly conserved program of neuronal microexons is misregulated in autistic brains","volume":"159","author":"M Irimia","year":"2014","journal-title":"Cell"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1008307","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2020,2,28]],"date-time":"2020-02-28T00:00:00Z","timestamp":1582848000000}},{"DOI":"10.1371\/journal.ppat.1012155","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T00:00:00Z","timestamp":1712620800000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1008307","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,2,28]],"date-time":"2020-02-28T13:37:15Z","timestamp":1582897035000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1008307"}},"subtitle":[],"editor":[{"given":"Edward M.","family":"Campbell","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2020,2,18]]},"references-count":83,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2020,2,18]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1008307","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.ppat.1008307","asserted-by":"object"}],"correction":[{"id-type":"doi","id":"10.1371\/journal.ppat.1012155","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,18]]}}}