Abstract:
:Poliovirus has been studied as a live recombinant vaccine vector because of its attractive characteristics. The genetic instability, however, has hampered recombinant polioviruses (PVs) from being developed as an appropriate vaccine. A variety of different foreign inserts were cloned directly into our poliovirus Sabin 1-based RPS-Vax vector system, resulting in the production of recombinant PVs. The genetic stability of each recombinant PV was examined during 12 rounds of consecutive passage. It was found that the genetic stability of the recombinants was not well correlated with their insert size. Instead, elevated stability was frequently observed in recombinants with inserts of high G/C contents. Furthermore, a comparative study using different constructs of the human immunodeficiency virus env gene revealed that the internal deletion of the unstable insert was seemingly caused by the presence of the adjacent A/T-rich region. The instability of these inserts was completely remedied by (i) increasing the G/C contents and (ii) replacing the local A/T-rich region with the G/C-rich codon without a change of the amino acid. This means that stability is closely associated with the G/C content and the G/C distribution pattern. To see whether these findings can be applied to the design of genetically stable recombinant PV, we have reconstructed the heteromultimeric insert based on our design architecture, including the above-mentioned G/C rules and the template/ligation-free PCR protocol. The heteromultimeric insert was very unstable, as expected, but the manipulated insert with the same amino acid sequence showed complete genetic stability, not only in vitro, but also in vivo. Even though this guideline was established with our RPS-Vax vector system, to some extent, it can also be applied to other live viral vaccine vectors.
journal_name
J Viroljournal_title
Journal of virologyauthors
Lee SG,Kim DY,Hyun BH,Bae YSdoi
10.1128/jvi.76.4.1649-1662.2002subject
Has Abstractpub_date
2002-02-01 00:00:00pages
1649-62issue
4eissn
0022-538Xissn
1098-5514journal_volume
76pub_type
杂志文章abstract::During the latent phase, Kaposi's sarcoma-associated herpes virus (KSHV) maintains itself inside the host by escaping the host immune surveillance mechanism through restricted protein expression. Latency-associated nuclear antigen (LANA), the most abundantly expressed protein, is essential for viral persistence, as it...
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journal_title:Journal of virology
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pub_type: 杂志文章
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更新日期:2009-10-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/JVI.69.2.916-922.1995
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pub_type: 杂志文章
doi:10.1128/jvi.74.24.11977-11982.2000
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pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.4.1517-1522.1990
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journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.17.8910-8919.2002
更新日期:2002-09-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.14.7465-7477.2004
更新日期:2004-07-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.8.5997-6002.1997
更新日期:1997-08-01 00:00:00
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pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.59.2.494-499.1986
更新日期:1986-08-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.8.2614-2620.1987
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pub_type: 杂志文章
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更新日期:1990-02-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章,评审
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更新日期:2016-06-10 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:1984-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:1998-10-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2017-02-28 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2000-12-01 00:00:00
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pub_type: 共识发展会议,杂志文章
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