{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T17:51:44Z","timestamp":1725904304065},"reference-count":58,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2014,12,1]],"date-time":"2014-12-01T00:00:00Z","timestamp":1417392000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            In the absence of universally available antiretroviral (ARV) drugs or a vaccine against HIV-1, microbicides may offer the most immediate hope for controlling the AIDS pandemic. The most advanced and clinically effective microbicides are based on ARV agents that interfere with the earliest stages of HIV-1 replication. Our objective was to identify and characterize novel ARV-like inhibitors, as well as demonstrate their efficacy at blocking HIV-1 transmission. Abasic phosphorothioate 2\u2032 deoxyribose backbone (PDB) oligomers were evaluated in a variety of mechanistic assays and for their ability to inhibit HIV-1 infection and virus transmission through primary human cervical mucosa. Cellular and biochemical assays were used to elucidate the antiviral mechanisms of action of PDB oligomers against both lab-adapted and primary CCR5- and CXCR4-utilizing HIV-1 strains, including a multidrug-resistant isolate. A polarized cervical organ culture was used to test the ability of PDB compounds to block HIV-1 transmission to primary immune cell populations across ectocervical tissue. The antiviral activity and mechanisms of action of PDB-based compounds were dependent on oligomer size, with smaller molecules preventing reverse transcription and larger oligomers blocking viral entry. Importantly, irrespective of molecular size, PDBs potently inhibited virus infection and transmission within genital tissue samples. Furthermore, the PDB inhibitors exhibited excellent toxicity and stability profiles and were found to be safe for vaginal application\n            <jats:italic>in vivo<\/jats:italic>\n            . These results, coupled with the previously reported intrinsic anti-inflammatory properties of PDBs, support further investigations in the development of PDB-based topical microbicides for preventing the global spread of HIV-1.\n          <\/jats:p>","DOI":"10.1128\/aac.02991-14","type":"journal-article","created":{"date-parts":[[2014,9,16]],"date-time":"2014-09-16T08:27:40Z","timestamp":1410856060000},"page":"7056-7071","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Abasic Phosphorothioate Oligomers Inhibit HIV-1 Reverse Transcription and Block Virus Transmission across Polarized Ectocervical Organ Cultures"],"prefix":"10.1128","volume":"58","author":[{"given":"Joseph A.","family":"Fraietta","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology and Center for Immunology and Vaccine Science, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yvonne M.","family":"Mueller","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and Center for Immunology and Vaccine Science, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karissa L.","family":"Lozenski","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and Center for Immunology and Vaccine Science, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deena","family":"Ratner","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alina C.","family":"Boesteanu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and Center for Immunology and Vaccine Science, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aidan S.","family":"Hancock","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and Center for Immunology and Vaccine Science, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carol","family":"Lackman-Smith","sequence":"additional","affiliation":[{"name":"Southern Research Institute, Frederick, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isaac J.","family":"Zentner","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irwin M.","family":"Chaiken","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suhman","family":"Chung","sequence":"additional","affiliation":[{"name":"HIV Drug Resistance Program, National Cancer Institute, National Institutes of Health, Frederick, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stuart F. J.","family":"LeGrice","sequence":"additional","affiliation":[{"name":"HIV Drug Resistance Program, National Cancer Institute, National Institutes of Health, Frederick, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beth A.","family":"Snyder","sequence":"additional","affiliation":[{"name":"Southern Research Institute, Frederick, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie K.","family":"Mankowski","sequence":"additional","affiliation":[{"name":"Southern Research Institute, Frederick, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie M.","family":"Jones","sequence":"additional","affiliation":[{"name":"Southern Research Institute, Frederick, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer L.","family":"Hope","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and Center for Immunology and Vaccine Science, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phalguni","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon H.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Obstetrics &amp; Gynecology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA"},{"name":"Main Line Fertility Center, Bryn Mawr, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Wigdahl","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and Center for Immunology and Vaccine Science, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter D.","family":"Katsikis","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and Center for Immunology and Vaccine Science, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","volume-title":"Global report: UNAIDS report on the global AIDS epidemic 2013","author":"UNAIDS","year":"2013","unstructured":"UNAIDS. 2013. Global report: UNAIDS report on the global AIDS epidemic 2013. United Nations Programme on HIV\/AIDS (UNAIDS), Geneva, Switzerland. http:\/\/www.unaids.org\/en\/media\/unaids\/contentassets\/documents\/epidemiology\/2013\/gr2013\/UNAIDS_Global_Report_2013_en.pdf."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.14.2.327-335.2001"},{"key":"e_1_3_2_4_2","volume-title":"AIDS epidemic update: December 2009","author":"United Nations Programme on HIV\/AIDS (UNAIDS)","year":"2009","unstructured":"United Nations Programme on HIV\/AIDS (UNAIDS). 2009. AIDS epidemic update: December 2009. United Nations Programme on HIV\/AIDS (UNAIDS), Geneva, Switzerland. http:\/\/data.unaids.org\/pub\/report\/2009\/jc1700_epi_update_2009_en.pdf."},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11908-005-0027-8"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0277-9536(93)90352-5"},{"issue":"99","key":"e_1_3_2_7_2","first-page":"37","article-title":"The female condom: expanding contraceptive options","author":"Mishra S","year":"1997","unstructured":"MishraS. 1997. The female condom: expanding contraceptive options. Manushi (99):37\u201338.","journal-title":"Manushi"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001474"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.2307\/1966433"},{"key":"e_1_3_2_10_2","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1089\/jwh.1998.7.1081","article-title":"Observations from the CDC. The urgent need for new HIV\/STD prevention options for women","volume":"7","author":"Irwin K","year":"1998","unstructured":"IrwinKScarlettMMoseleyR. 1998. Observations from the CDC. The urgent need for new HIV\/STD prevention options for women. J. Womens Health 7:1081\u20131086.","journal-title":"J. Womens Health"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/453289a"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1011205"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1193748"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60877-5"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)11079-8"},{"key":"e_1_3_2_16_2","volume-title":"Safety and effectiveness of vaginal microbicides BufferGel and 0.5% PRO 2000\/5 gel for the prevention of HIV infection in women: results of the HPTN 035 trial","author":"Karim SAC","year":"2009","unstructured":"KarimSACRichardsonBRamjeeGHoffmanIChirenjeMTahaTKapinaMMaslankowskiLSoto-TorresL. 2009. Safety and effectiveness of vaginal microbicides BufferGel and 0.5% PRO 2000\/5 gel for the prevention of HIV infection in women: results of the HPTN 035 trial. 16th Conference on Retroviruses and Opportunistic Infections, 8 to 11 February 2009, Montreal, Canada."},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI32291"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61086-0"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003784"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001312"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e3283522272"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00367-10"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.01.013"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.11.8164"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.10.6584"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.3.487"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1177\/1087057105282959"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1089\/aid.1991.7.295"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(90)90059-Z"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1089\/088922202320886325"},{"key":"e_1_3_2_31_2","first-page":"359","article-title":"Disposition of tricyclic nucleoside-5\u2032-monophosphate in blood and plasma of patients during phase I and II clinical trials","volume":"70","author":"Powis G","year":"1986","unstructured":"PowisGBassechesPJKroschelDMRichardsonRLO'ConnellMJKvolsLK. 1986. Disposition of tricyclic nucleoside-5\u2032-monophosphate in blood and plasma of patients during phase I and II clinical trials. Cancer Treat Rep. 70:359\u2013362.","journal-title":"Cancer Treat Rep."},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01328-07"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01443-09"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201000222"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-59745-170-3_5"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00434-10"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00274-08"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.8.3740-3751.2000"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-0934(88)90134-6"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/74743"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e318258b420"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1777"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.354373"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0020142"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1848"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clae.2009.05.004"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-080709-124959"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpobgyn.2012.02.002"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.22.14355-14370.2005"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07831"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00701-013-1723-z"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05801-11"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002634"},{"key":"e_1_3_2_54_2","first-page":"S119","article-title":"Vaginal transmission of SIV: assessing infectivity and hormonal influences in macaques inoculated with cell-free and cell-associated viral stocks","volume":"14","author":"Sodora DL","year":"1998","unstructured":"SodoraDLGettieAMillerCJMarxPA. 1998. Vaginal transmission of SIV: assessing infectivity and hormonal influences in macaques inoculated with cell-free and cell-associated viral stocks. AIDS Res. Hum. Retroviruses 14(Suppl 1):S119\u2013S123.","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06106"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1974"},{"key":"e_1_3_2_57_2","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1089\/ard.1993.3.19","article-title":"Phosphorothioate oligodeoxynucleotides bind to the third variable loop domain (v3) of human immunodeficiency virus type 1 gp120","volume":"3","author":"Stein CA","year":"1993","unstructured":"SteinCAClearyAMYakubovLLedermanS. 1993. Phosphorothioate oligodeoxynucleotides bind to the third variable loop domain (v3) of human immunodeficiency virus type 1 gp120. Antisense Res. Dev. 3:19\u201331.","journal-title":"Antisense Res. Dev."},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(73)90418-X"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.socscimed.2004.05.011"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.02991-14","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.02991-14","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T22:42:39Z","timestamp":1645483359000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.02991-14"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,12]]},"references-count":58,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2014,12]]}},"alternative-id":["10.1128\/AAC.02991-14"],"URL":"https:\/\/doi.org\/10.1128\/aac.02991-14","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,12]]},"assertion":[{"value":"2014-04-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-09-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-11-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}