{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:33:59Z","timestamp":1787016839928,"version":"build-2736575974"},"reference-count":57,"publisher":"American Society for Microbiology","issue":"20","license":[{"start":{"date-parts":[[2018,10,15]],"date-time":"2018-10-15T00:00:00Z","timestamp":1539561600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Gouvernement du Canada | Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["IBC150405"],"award-info":[{"award-number":["IBC150405"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2018,10,15]]},"abstract":"<jats:p>\n                    The results of this study demonstrate that the gene-editing complex Cas9\/sgRNA can be programmed to target and cleave HIV-1 PBS DNA, and thus, inhibit HIV-1 infection. Given that almost all HIV-1 strains have the same PBS, which is copied from the cellular tRNA\n                    <jats:sub arrange=\"stack\">3<\/jats:sub>\n                    <jats:sup arrange=\"stack\">Lys<\/jats:sup>\n                    during reverse transcription, PBS-targeting sgRNA can be used to inactivate HIV-1 DNA of different strains. We also discovered that HIV-1 uses different mechanisms to resist Cas9\/sgRNAs, depending on whether they target the plus or the minus strand of PBS DNA. These findings allow us to predict that a Cas9 variant that uses the CCA sequence as the protospacer adjacent motif (PAM) should more strongly and persistently suppress HIV-1 replication. Together, these data have identified the PBS as the target DNA of Cas9\/sgRNA and have predicted how to improve Cas9\/sgRNA to achieve more efficient and sustainable suppression of HIV-1 infection, therefore improving the capacity of Cas9\/sgRNA in curing HIV-1 infection.\n                  <\/jats:p>","DOI":"10.1128\/jvi.01135-18","type":"journal-article","created":{"date-parts":[[2018,8,1]],"date-time":"2018-08-01T05:51:46Z","timestamp":1533102706000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":29,"title":["HIV-1 Employs Multiple Mechanisms To Resist Cas9\/Single Guide RNA Targeting the Viral Primer Binding Site"],"prefix":"10.1128","volume":"92","author":[{"given":"Zhen","family":"Wang","sequence":"first","affiliation":[{"name":"Lady Davis Institute, Jewish General Hospital, Montreal, Canada"},{"name":"Department of Medicine, McGill University, Montreal, 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