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Full-length title: Dramatic HIV DNA degradation associated with spontaneous HIV suppression and disease-free outcome in a young seropositive woman following her infection

Scientific Reports. 2020;10(1):1-9 DOI 10.1038/s41598-020-58969-6

 

Journal Homepage

Journal Title: Scientific Reports

ISSN: 2045-2322 (Online)

Publisher: Nature Publishing Group

LCC Subject Category: Medicine | Science

Country of publisher: United Kingdom

Language of fulltext: English

Full-text formats available: PDF, HTML

 

AUTHORS


Philippe Colson (IHU Méditerranée Infection, 19-21 boulevard Jean Moulin)

Catherine Dhiver (IHU Méditerranée Infection, 19-21 boulevard Jean Moulin)

Catherine Tamalet (IHU Méditerranée Infection, 19-21 boulevard Jean Moulin)

Jeremy Delerce (IHU Méditerranée Infection, 19-21 boulevard Jean Moulin)

Olga O. Glazunova (IHU Méditerranée Infection, 19-21 boulevard Jean Moulin)

Maxime Gaudin (Aix-Marseille Univ., IRD, AP-HM, MEPHI, 19-21 boulevard Jean Moulin)

Anthony Levasseur (IHU Méditerranée Infection, 19-21 boulevard Jean Moulin)

Didier Raoult (IHU Méditerranée Infection, 19-21 boulevard Jean Moulin)

EDITORIAL INFORMATION

Blind peer review

Editorial Board

Instructions for authors

Time From Submission to Publication: 20 weeks

 

Abstract | Full Text

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.