No evidence of ongoing evolution in replication competent latent HIV-1 in a patient followed up for two years

Mok, H. P., Norton, N. J., Hirst, J. C., Fun, A., Bandara, M. , Wills, M. R. and Lever, A. M.L. (2018) No evidence of ongoing evolution in replication competent latent HIV-1 in a patient followed up for two years. Scientific Reports, 8, 2639. (doi: 10.1038/s41598-018-20682-w) (PMID:29422601) (PMCID:PMC5805784)

Abstract

The persistence of infected T cells harbouring intact HIV proviruses is the barrier to the eradication of HIV. This reservoir is stable over long periods of time despite antiretroviral therapy. There has been controversy on whether low level viral replication is occurring at sanctuary sites periodically reseeding infected cells into the latent reservoir to account its durability. To study viral evolution in a physiologically relevant population of latent viruses, we repeatedly performed virus outgrowth assays on a stably treated HIV positive patient over two years and sequenced the reactivated latent viruses. We sought evidence of increasing sequence pairwise distances with time as evidence of ongoing viral replication. 64 reactivatable latent viral sequences were obtained over 103 weeks. We did not observe an increase in genetic distance of the sequences with the time elapsed between sampling. No evolution could be discerned in these reactivatable latent viruses. Thus, in this patient, the contribution of low-level replication to the maintenance of the latent reservoir detectable in the blood compartment is limited.

• Item Type: Articles
• Additional Information: HPM and NJN are both supported by the Medical Research Council, UK (MR/N02043X/1 and MR/M003515/1 respectively). This project was supported by The Academy of Medical Sciences (UK), The Evelyn Trust, the Clinical Academic Reserve, and The British HIV Association. This work was submitted on behalf of the UK Biomedical Research Centres CHERUB cooperative and was supported by the National Institutes for Health Research (NIHR, Cambridge Biomedical Research Centre).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Jayaweera Bandara, Dr Mikaila
• Authors: Mok, H. P., Norton, N. J., Hirst, J. C., Fun, A., Bandara, M., Wills, M. R., and Lever, A. M.L.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Scientific Reports
• Publisher: Nature Research
• ISSN: 2045-2322
• ISSN (Online): 2045-2322
• Copyright Holders: Copyright © 2018 The Authors
• First Published: First published in Scientific Reports 8: 2639
• Publisher Policy: Reproduced under a Creative Commons License