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Collinearity of pro...
Collinearity of protease mutations in HIV-1 samples with high-level protease inhibitor class resistance
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Babrzadeh, F. (författare)
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Varghese, V. (författare)
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Pacold, M. (författare)
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Liu, T. F. (författare)
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- Nyrén, Pål (författare)
- KTH,Biokemi
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Schiffer, C. (författare)
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Fessel, W. J. (författare)
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Shafer, R. W. (författare)
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(creator_code:org_t)
- 2012-10-19
- 2013
- Engelska.
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 68:2, s. 414-418
- Relaterad länk:
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https://academic.oup...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Objectives: To determine whether pan-protease inhibitor (PI)-resistant virus populations are composed predominantly of viruses with resistance to all PIs or of diverse virus populations with resistance to different subsets of PIs. Methods: We performed deep sequencing of plasma virus samples from nine patients with high-level genotypic and/or phenotypic resistance to all licensed PIs. The nine virus samples had a median of 12 PI resistance mutations by direct PCR Sanger sequencing. Results: For each of the nine virus samples, deep sequencing showed that each of the individual viruses within a sample contained nearly all of the mutations detected by Sanger sequencing. Indeed, a median of 94.9% of deep sequence reads had each of the PI resistance mutations present as a single chromatographic peak in the Sanger sequence. A median of 5.0% of reads had all but one of the Sanger mutations that were not part of an electrophoretic mixture. Conclusions: The collinearity of PI resistance mutations in the nine virus samples demonstrated that pan-PI-resistant viruses are able to replicate in vivo despite their highly mutated protease enzymes. We hypothesize that the marked collinearity of PI resistance mutations in pan-PI-resistant virus populations results from the unique requirements for multi-PI resistance and the extensive cross-resistance conferred by many of the accessory PI resistance mutations.
Nyckelord
- Deep sequencing
- Drug resistance
- Minority variants
- Sanger sequencing
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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