{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T18:30:00Z","timestamp":1773081000789,"version":"3.50.1"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Retrovirology"],"published-print":{"date-parts":[[2007,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Human immunodeficiency virus type 1 (HIV-1) can be inhibited by means of RNA silencing or interference (RNAi) using synthetic short interfering RNAs (siRNAs) or gene constructs encoding short hairpin RNAs (shRNAs) or long hairpin RNAs (lhRNAs). The use of siRNA and shRNA as antiviral therapeutic is limited because of the emergence of viral escape mutants. This problem is theoretically prevented by intracellular expression of lhRNAs generating multiple siRNAs that target the virus simultaneously, thus reducing the chance of viral escape. However, gene constructs encoding lhRNA molecules face problems with delivery to the right cells in an infected individual. In order to solve this problem, we constructed an HIV-1 variant with a 300 bp long hairpin structure in the 3' part of the genome corresponding to the Nef gene (HIV-lhNef).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Intriguingly, HIV-lhNef potently inhibited wild-type HIV-1 production in trans. However, HIV-lhNef demonstrated a severe production and replication defect, which we were able to solve by selecting spontaneous virus variants with truncated hairpin structures. Although these escape variants lost the ability to trans-inhibit HIV-1, they effectively outgrew the wild-type virus in competition experiments in SupT1 cells.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Expression of the lhNef hairpin within the HIV-1 genome results in potent trans-inhibition of wild-type HIV-1. Although the mechanism of trans-inhibition is currently unknown, it remains of interest to study the molecular details because the observed effect is extremely potent. This may have implications for the development of virus strains to be used as live-attenuated virus vaccines.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1742-4690-4-15","type":"journal-article","created":{"date-parts":[[2007,3,2]],"date-time":"2007-03-02T00:54:05Z","timestamp":1172796845000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Trans-inhibition of HIV-1 by a long hairpin RNA expressed within the viral genome"],"prefix":"10.1186","volume":"4","author":[{"given":"Pavlina","family":"Konstantinova","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivier","family":"ter Brake","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joost","family":"Haasnoot","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"de Haan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ben","family":"Berkhout","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2007,3,1]]},"reference":[{"key":"744_CR1","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1007\/BF02256311","volume":"10","author":"PCJ Haasnoot","year":"2003","unstructured":"Haasnoot PCJ, Cupac D, Berkhout B: Inhibition of virus replication by RNA interference. J Biomed Sc. 2003, 10: 607-616.","journal-title":"J Biomed Sc"},{"key":"744_CR2","doi-asserted-by":"publisher","first-page":"2896","DOI":"10.1016\/j.febslet.2006.02.070","volume":"580","author":"B Berkhout","year":"2006","unstructured":"Berkhout B, Haasnoot J: The interplay between virus infection and the cellular RNA interference machinery. FEBS Lett. 2006, 580: 2896-2902. 10.1016\/j.febslet.2006.02.070.","journal-title":"FEBS Lett"},{"key":"744_CR3","doi-asserted-by":"publisher","first-page":"5196","DOI":"10.4049\/jimmunol.169.9.5196","volume":"169","author":"J Capodici","year":"2002","unstructured":"Capodici J, Kariko K, Weissman D: Inhibition of HIV-1 infection by small interfering RNA-mediated RNA interference. J Immunol. 2002, 169: 5196-5201.","journal-title":"J Immunol"},{"key":"744_CR4","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1038\/nature00896","volume":"418","author":"JM Jacque","year":"2002","unstructured":"Jacque JM, Triques K, Stevenson M: Modulation of HIV-1 replication by RNA interference. Nature. 2002, 418: 435-438. 10.1038\/nature00896.","journal-title":"Nature"},{"key":"744_CR5","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1038\/nm725","volume":"8","author":"CD Novina","year":"2002","unstructured":"Novina CD, Murray MF, Dykxhoorn DM, Beresford PJ, Riess J, Lee SK, Collman RG, Lieberman J, Shankar P, Sharp PA: siRNA-directed inhibition of HIV-1 infection. Nat Med. 2002, 8: 681-686.","journal-title":"Nat Med"},{"key":"744_CR6","doi-asserted-by":"publisher","first-page":"4830","DOI":"10.1093\/nar\/gkf627","volume":"30","author":"WS Park","year":"2002","unstructured":"Park WS, Miyano-Kurosaki N, Hayafune M, Nakajima E, Matsuzaki T, Shimada F, Takaku H: Prevention of HIV-1 infection in human peripheral blood mononuclear cells by specific RNA interference. Nucleic Acids Res. 2002, 30: 4830-4835. 10.1093\/nar\/gkf627.","journal-title":"Nucleic Acids Res"},{"key":"744_CR7","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1089\/154545703322616989","volume":"13","author":"J Anderson","year":"2003","unstructured":"Anderson J, Banerjea A, Akkina R: Bispecific short hairpin siRNA constructs targeted to CD4, CXCR4, and CCR5 confer HIV-1 resistance. Oligonucleotides. 2003, 13: 303-312. 10.1089\/154545703322616989.","journal-title":"Oligonucleotides"},{"key":"744_CR8","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1093\/nar\/gkh278","volume":"32","author":"D Boden","year":"2004","unstructured":"Boden D, Pusch O, Silbermann R, Lee F, Tucker L, Ramratnam B: Enhanced gene silencing of HIV-1 specific siRNA using microRNA designed hairpins. Nucleic Acids Res. 2004, 32: 1154-1158. 10.1093\/nar\/gkh278.","journal-title":"Nucleic Acids Res"},{"key":"744_CR9","doi-asserted-by":"publisher","first-page":"2601","DOI":"10.1128\/JVI.78.5.2601-2605.2004","volume":"78","author":"AT Das","year":"2004","unstructured":"Das AT, Brummelkamp TR, Westerhout EM, Vink M, Madiredjo M, Bernards R, Berkhout B: Human immunodeficiency virus type 1 escapes from RNA interference-mediated inhibition. J Virol. 2004, 78: 2601-2605. 10.1128\/JVI.78.5.2601-2605.2004.","journal-title":"J Virol"},{"key":"744_CR10","doi-asserted-by":"publisher","first-page":"11531","DOI":"10.1128\/JVI.77.21.11531-11535.2003","volume":"77","author":"D Boden","year":"2003","unstructured":"Boden D, Pusch O, Lee F, Tucker L, Ramratnam B: Human immunodeficiency virus type 1 escape from RNA interference. J Virol. 2003, 77: 11531-11535. 10.1128\/JVI.77.21.11531-11535.2003.","journal-title":"J Virol"},{"key":"744_CR11","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1093\/nar\/gki220","volume":"33","author":"EM Westerhout","year":"2005","unstructured":"Westerhout EM, Ooms M, Vink M, Das AT, Berkhout B: HIV-1 can escape from RNA interference by evolving an alternative structure in its RNA genome. Nucleic Acids Res. 2005, 33: 796-804. 10.1093\/nar\/gki220.","journal-title":"Nucleic Acids Res"},{"key":"744_CR12","first-page":"141","volume":"6","author":"B Berkhout","year":"2004","unstructured":"Berkhout B: RNA interference as an antiviral approach: targeting HIV-1. Curr Opin Mol Ther. 2004, 6: 141-145.","journal-title":"Curr Opin Mol Ther"},{"key":"744_CR13","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1016\/j.ymthe.2006.07.007","volume":"14","author":"O Ter Brake","year":"2006","unstructured":"Ter Brake O, Konstantinova P, Ceylan M, Berkhout B: Silencing of HIV-1 with RNA Interference: a multiple shRNA approach. Mol Ther. 2006, 14: 883-892. 10.1016\/j.ymthe.2006.07.007.","journal-title":"Mol Ther"},{"key":"744_CR14","first-page":"56","volume":"1(2)","author":"O Ter Brake","year":"2005","unstructured":"Ter Brake O, Berkhout B: A novel approach for inhibition of HIV-1 by RNA interference: counteracting viral escape with a second generation of siRNAs. Journal of RNAi and Gene Silencing. 2005, 1(2): 56-65.","journal-title":"Journal of RNAi and Gene Silencing"},{"key":"744_CR15","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1186\/1742-4690-2-81","volume":"2","author":"ML Yeung","year":"2005","unstructured":"Yeung ML, Bennasser Y, Myers TG, Jiang G, Benkirane M, Jeang KT: Changes in microRNA expression profiles in HIV-1-transfected human cells. Retrovirology. 2005, 2: 81-10.1186\/1742-4690-2-81.","journal-title":"Retrovirology"},{"key":"744_CR16","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.1016\/j.bbrc.2005.09.183","volume":"337","author":"M Hariharan","year":"2005","unstructured":"Hariharan M, Scaria V, Pillai B, Brahmachari SK: Targets for human encoded microRNAs in HIV genes. Biochem Biophys Res Commun. 2005, 337: 1214-1218. 10.1016\/j.bbrc.2005.09.183.","journal-title":"Biochem Biophys Res Commun"},{"key":"744_CR17","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1111\/j.1348-0421.2002.tb02768.x","volume":"46","author":"T Yamamoto","year":"2002","unstructured":"Yamamoto T, Omoto S, Mizuguchi M, Mizukami H, Okuyama H, Okada N, Saksena NK, Brisibe EA, Otake K, Fuji YR: Double-stranded nef RNA interferes with human immunodeficiency virus type 1 replication. Microbiol Immunol. 2002, 46: 809-817.","journal-title":"Microbiol Immunol"},{"key":"744_CR18","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1038\/sj.gt.3302786","volume":"13","author":"P Konstantinova","year":"2006","unstructured":"Konstantinova P, de Vries W, Haasnoot J, Ter Brake O, de Haan P, Berkhout B: Inhibition of human immunodeficiency virus type 1 by RNA interference using long-hairpin RNA. Gene Ther. 2006, 13: 1403-1413. 10.1038\/sj.gt.3302786.","journal-title":"Gene Ther"},{"key":"744_CR19","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1039\/b510159j","volume":"1","author":"H Akashi","year":"2005","unstructured":"Akashi H, Miyagishi M, Yokota T, Watanabe H, Hino T, Nishina K, Kohara M, Taira K: Escape from the interferon response associated with RNA interference using vectors that encode long modified hairpin-RNA. Molecular BioSystems. 2005, 1: 382-390. 10.1039\/b510159j.","journal-title":"Molecular BioSystems"},{"key":"744_CR20","doi-asserted-by":"publisher","first-page":"25687","DOI":"10.1074\/jbc.M412784200","volume":"280","author":"S Matsumoto","year":"2005","unstructured":"Matsumoto S, Miyagishi M, Akashi H, Nagai R, Taira K: Analysis of double-stranded RNA-induced apoptosis pathways using interferon-response noninducible small interfering RNA expression vector library. J Biol Chem. 2005, 280: 25687-25696. 10.1074\/jbc.M412784200.","journal-title":"J Biol Chem"},{"key":"744_CR21","doi-asserted-by":"publisher","first-page":"7658","DOI":"10.1128\/JVI.00078-06","volume":"80","author":"H Nishitsuji","year":"2006","unstructured":"Nishitsuji H, Kohara M, Kannagi M, Masuda T: Effective suppression of human immunodeficiency virus type 1 through a combination of short- or long-hairpin RNAs targeting essential sequences for retroviral integration. J Virol. 2006, 80: 7658-7666. 10.1128\/JVI.00078-06.","journal-title":"J Virol"},{"key":"744_CR22","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1101\/gad.862301","volume":"15","author":"SM Elbashir","year":"2001","unstructured":"Elbashir SM, Lendeckel W, Tuschl T: RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes Dev. 2001, 15: 188-200. 10.1101\/gad.862301.","journal-title":"Genes Dev"},{"key":"744_CR23","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1006\/mthe.2002.0652","volume":"6","author":"NJ Caplen","year":"2002","unstructured":"Caplen NJ, Zheng Z, Falgout B, Morgan RA: Inhibition of viral gene expression and replication in mosquito cells by dsRNA-triggered RNA interference. Mol Ther. 2002, 6: 243-251. 10.1006\/mthe.2002.0652.","journal-title":"Mol Ther"},{"key":"744_CR24","doi-asserted-by":"publisher","first-page":"e179","DOI":"10.1093\/nar\/gnh180","volume":"32","author":"Y Qi","year":"2004","unstructured":"Qi Y, Zhong X, Itaya A, Ding B: Dissecting RNA silencing in protoplasts uncovers novel effects of viral suppressors on the silencing pathway at the cellular level. Nucleic Acids Res. 2004, 32: e179-10.1093\/nar\/gnh180.","journal-title":"Nucleic Acids Res"},{"key":"744_CR25","doi-asserted-by":"publisher","first-page":"13959","DOI":"10.1073\/pnas.95.23.13959","volume":"95","author":"PM Waterhouse","year":"1998","unstructured":"Waterhouse PM, Graham MW, Wang MB: Virus resistance and gene silencing in plants can be induced by simultaneous expression of sense and antisense RNA. Proc Natl Acad Sci USA. 1998, 95: 13959-13964. 10.1073\/pnas.95.23.13959.","journal-title":"Proc Natl Acad Sci USA"},{"key":"744_CR26","doi-asserted-by":"publisher","first-page":"12925","DOI":"10.1128\/JVI.76.24.12925-12933.2002","volume":"76","author":"ZN Adelman","year":"2002","unstructured":"Adelman ZN, Sanchez-Vargas I, Travanty EA, Carlson JO, Beaty BJ, Blair CD, Olson KE: RNA silencing of dengue virus type 2 replication in transformed C6\/36 mosquito cells transcribing an inverted-repeat RNA derived from the virus genome. J Virol. 2002, 76: 12925-12933. 10.1128\/JVI.76.24.12925-12933.2002.","journal-title":"J Virol"},{"key":"744_CR27","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1016\/j.ymthe.2006.03.018","volume":"14","author":"EM Westerhout","year":"2006","unstructured":"Westerhout EM, Vink M, Haasnoot PC, Das AT, Berkhout B: A conditionally replicating HIV-based vector that stably expresses an antiviral shRNA against HIV-1 replication. Mol Ther. 2006, 14: 268-275. 10.1016\/j.ymthe.2006.03.018.","journal-title":"Mol Ther"},{"key":"744_CR28","doi-asserted-by":"publisher","first-page":"2206","DOI":"10.1093\/nar\/gkl226","volume":"34","author":"P Konstantinova","year":"2006","unstructured":"Konstantinova P, de Haan P, Das AT, Berkhout B: Hairpin-induced tRNA-mediated (HITME) recombination in HIV-1. Nucleic Acids Res. 2006, 34: 2206-2218. 10.1093\/nar\/gkl226.","journal-title":"Nucleic Acids Res"},{"key":"744_CR29","doi-asserted-by":"publisher","first-page":"4130","DOI":"10.1093\/nar\/28.21.4130","volume":"28","author":"N Beerens","year":"2000","unstructured":"Beerens N, Groot F, Berkhout B: Stabilization of the U5-leader stem in the HIV-1 RNA genome affects initiation and elongation of reverse transcription. Nucleic Acids Res. 2000, 28: 4130-4137. 10.1093\/nar\/28.21.4130.","journal-title":"Nucleic Acids Res"},{"key":"744_CR30","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/0042-6822(92)90772-H","volume":"188","author":"A de Ronde","year":"1992","unstructured":"de Ronde A, Klaver B, Keulen W, Smit L, Goudsmit J: Natural HIV-1 NEF accelerates virus replication in primary human lymphocytes. Virol. 1992, 188: 391-395. 10.1016\/0042-6822(92)90772-H.","journal-title":"Virol"},{"key":"744_CR31","doi-asserted-by":"publisher","first-page":"988","DOI":"10.1126\/science.270.5238.988","volume":"270","author":"NJ Deacon","year":"1995","unstructured":"Deacon NJ, Tsykin A, Solomon A, Smith K, Ludford-Menting M, Hooker DJ, McPhee DA, Greenway AL, Ellett A, Chatfield C, Lawson VA, Crowe S, Maerz A, Sonza S, Learmont J, Sullivan JS, Cunningham A, Dwyer D, Dowton D, Mills J: Genomic structure of an attenuated quasi species of HIV-1 from blood transfusion donor and recipients. Science. 1995, 270: 988-991. 10.1126\/science.270.5238.988.","journal-title":"Science"},{"key":"744_CR32","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1038\/nature01749","volume":"424","author":"S Swingler","year":"2003","unstructured":"Swingler S, Brichacek B, Jacque JM, Ulich C, Zhou J, Stevenson M: HIV-1 Nef intersects the macrophage CD40L signalling pathway to promote resting-cell infection. Nature. 2003, 424: 213-219. 10.1038\/nature01749.","journal-title":"Nature"},{"key":"744_CR33","doi-asserted-by":"publisher","first-page":"22996","DOI":"10.1074\/jbc.M312453200","volume":"279","author":"I Schiavoni","year":"2004","unstructured":"Schiavoni I, Trapp S, Santarcangelo AC, Piacentini V, Pugliese K, Baur A, Federico M: HIV-1 Nef enhances both membrane expression and virion incorporation of Env products. A model for the Nef-dependent increase of HIV-1 infectivity. J Biol Chem. 2004, 279: 22996-23006. 10.1074\/jbc.M312453200.","journal-title":"J Biol Chem"},{"key":"744_CR34","doi-asserted-by":"publisher","first-page":"3305","DOI":"10.1182\/blood-2006-04-014829","volume":"108","author":"T Yamamoto","year":"2006","unstructured":"Yamamoto T, Miyoshi H, Yamamoto N, Yamamoto N, Inoue J, Tsunetsugu-Yokota Y: Lentivirus vectors expressing short hairpin RNAs against the U3-overlapping region of HIV nef inhibit HIV replication and infectivity in primary macrophages. Blood. 2006, 108: 3305-3312. 10.1182\/blood-2006-04-014829.","journal-title":"Blood"},{"key":"744_CR35","doi-asserted-by":"publisher","first-page":"10581","DOI":"10.1128\/JVI.74.22.10581-10588.2000","volume":"74","author":"DI Rhodes","year":"2000","unstructured":"Rhodes DI, Ashton L, Solomon A, Carr A, Cooper D, Kaldor J, Deacon N: Characterization of three nef-defective human immunodeficiency virus type 1 strains associated with long-term nonprogression. Australian Long-Term Nonprogressor Study Group. J Virol. 2000, 74: 10581-10588. 10.1128\/JVI.74.22.10581-10588.2000.","journal-title":"J Virol"},{"key":"744_CR36","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1038\/5515","volume":"5","author":"RP Johnson","year":"1999","unstructured":"Johnson RP: Live attenuated AIDS vaccines: hazards and hopes. Nature Medicine. 1999, 5: 154-155. 10.1038\/5515.","journal-title":"Nature Medicine"},{"key":"744_CR37","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/j.virol.2004.09.026","volume":"330","author":"R Stebbings","year":"2004","unstructured":"Stebbings R, Berry N, Stott J, Hull R, Walker B, Lines J, Elsley W, Brown S, Wade-Evans A, Davis G, Cowie J, Sethi M, Almond N: Vaccination with live attenuated simian immunodeficiency virus for 21 days protects against superinfection. Virol. 2004, 330: 249-260. 10.1016\/j.virol.2004.09.026.","journal-title":"Virol"},{"key":"744_CR38","doi-asserted-by":"publisher","first-page":"4914","DOI":"10.1128\/JVI.78.9.4914-4916.2004","volume":"78","author":"JL Bromberg-White","year":"2004","unstructured":"Bromberg-White JL, Webb CP, Patacsil VS, Miranti CK, Williams BO, Holmen SL: Delivery of short hairpin RNA sequences by using a replication-competent avian retroviral vector. J Virol. 2004, 78: 4914-4916. 10.1128\/JVI.78.9.4914-4916.2004.","journal-title":"J Virol"},{"key":"744_CR39","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1016\/j.virol.2006.03.014","volume":"351","author":"K Sliva","year":"2006","unstructured":"Sliva K, Schnierle BS: Stable integration of a functional shRNA expression cassette into the murine leukemia virus genome. Virol. 2006, 351: 218-225.","journal-title":"Virol"},{"issue":"3","key":"744_CR40","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1038\/sj.mt.6300077","volume":"15","author":"MS Weinberg","year":"2007","unstructured":"Weinberg MS, Ely A, Barichievy S, Crowther C, Mufamadi S, Carmona S, Arbuthnot P: Specific Inhibition of HBV Replication In Vitro and In Vivo With Expressed Long Hairpin RNA. Mol Ther. 2007, 15 (3): 534-41. 10.1038\/sj.mt.6300077.","journal-title":"Mol Ther"},{"key":"744_CR41","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1016\/0042-6822(91)90537-L","volume":"185","author":"K Peden","year":"1991","unstructured":"Peden K, Emerman M, Montagnier L: Changes in growth properties on passage in tissue culture of viruses derived from infectious molecular clones of HIV-1LAI, HIV-1MAL, and HIV-1ELI. Virol. 1991, 185: 661-672. 10.1016\/0042-6822(91)90537-L.","journal-title":"Virol"},{"key":"744_CR42","doi-asserted-by":"publisher","first-page":"3406","DOI":"10.1093\/nar\/gkg595","volume":"31","author":"M Zuker","year":"2003","unstructured":"Zuker M: Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res. 2003, 31: 3406-3415. 10.1093\/nar\/gkg595.","journal-title":"Nucleic Acids Res"},{"key":"744_CR43","doi-asserted-by":"publisher","first-page":"3740","DOI":"10.1128\/JVI.74.8.3740-3751.2000","volume":"74","author":"RE Jeeninga","year":"2000","unstructured":"Jeeninga RE, Hoogenkamp M, Armand-Ugon M, de Baar M, Verhoef K, Berkhout B: Functional differences between the long terminal repeat transcriptional promoters of HIV-1 subtypes A through G. J Virol. 2000, 74: 3740-3751. 10.1128\/JVI.74.8.3740-3751.2000. [http:\/\/PM:10729149]","journal-title":"J Virol"}],"container-title":["Retrovirology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1742-4690-4-15.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T23:45:44Z","timestamp":1630453544000},"score":1,"resource":{"primary":{"URL":"https:\/\/retrovirology.biomedcentral.com\/articles\/10.1186\/1742-4690-4-15"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,3,1]]},"references-count":43,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2007,12]]}},"alternative-id":["744"],"URL":"https:\/\/doi.org\/10.1186\/1742-4690-4-15","relation":{},"ISSN":["1742-4690"],"issn-type":[{"value":"1742-4690","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,3,1]]},"assertion":[{"value":"6 December 2006","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 March 2007","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 March 2007","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"15"}}