Abstract |
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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Authors | Philippe Colson, Catherine Dhiver, Catherine Tamalet, Jeremy Delerce, Olga O Glazunova, Maxime Gaudin, Anthony Levasseur, Didier Raoult |
Journal | Scientific reports
(Sci Rep)
Vol. 10
Issue 1
Pg. 2548
(02 13 2020)
ISSN: 2045-2322 [Electronic] England |
PMID | 32054885
(Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't, Retracted Publication)
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Chemical References |
- Codon, Terminator
- DNA, Viral
- Tryptophan
- APOBEC Deaminases
- APOBEC3 proteins, human
- Cytidine Deaminase
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Topics |
- APOBEC Deaminases
- Codon, Terminator
(genetics)
- Cytidine Deaminase
(genetics)
- DNA, Viral
(genetics, isolation & purification)
- Female
- Gastrointestinal Microbiome
(genetics)
- Genome, Viral
(genetics)
- HIV Infections
(epidemiology, genetics, virology)
- HIV Seropositivity
(genetics)
- HIV-1
(genetics, pathogenicity)
- Humans
- Mutation
(genetics)
- Tryptophan
(genetics)
- Virus Replication
(genetics)
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