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  • 标题:Full-length title: Dramatic HIV DNA degradation associated with spontaneous HIV suppression and disease-free outcome in a young seropositive woman following her infection
  • 本地全文:下载
  • 作者:Philippe Colson ; Catherine Dhiver ; Catherine Tamalet
  • 期刊名称:Scientific Reports
  • 电子版ISSN:2045-2322
  • 出版年度:2020
  • 卷号:10
  • 期号:1
  • 页码:1-9
  • DOI:10.1038/s41598-020-58969-6
  • 出版社:Springer Nature
  • 摘要:Strategies to cure HIV-infected patients by virus-targeting drugs have failed to date. We identified a HIV-1-seropositive woman who spontaneously suppressed HIV replication and had normal CD4-cell counts, no HIV-disease, no replication-competent virus and no cell HIV DNA detected with a routine assay. We suspected that dramatic HIV DNA degradation occurred post-infection. We performed multiple nested-PCRs followed by Sanger sequencing and applied a multiplex-PCR approach. Furthermore, we implemented a new technique based on two hybridization steps on beads prior to next-generation sequencing that removed human DNA then retrieved integrated HIV sequences with HIV-specific probes. We assembled ≈45% of the HIV genome and further analyzed the G-to-A mutations putatively generated by cellular APOBEC3 enzymes that can change tryptophan codons into stop codons. We found more G-to-A mutations in the HIV DNA from the woman than in that of her transmitting partner. Moreover, 74% of the tryptophan codons were changed to stop codons (25%) or were deleted as a possible consequence of gene inactivation. Finally, we found that this woman’s cells remained HIV-susceptible in vitro . Our findings show that she does not exhibit innate HIV-resistance but may have been cured of it by extrinsic factors, a plausible candidate for which is the gut microbiota.
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