No evidence of ongoing evolution in replication competent latent HIV-1 in a patient followed up for two years.
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Authors
Norton, Nicholas
Bandara, Mikaila
Lever, Andrew
Publication Date
2018-02-08Journal Title
Sci Rep
ISSN
2045-2322
Publisher
Springer Science and Business Media LLC
Volume
8
Issue
1
Pages
2639
Language
eng
Type
Article
This Version
VoR
Physical Medium
Electronic
Metadata
Show full item recordCitation
Mok, H. P., Norton, N., Hirst, J. C., Fun, A., Bandara, M., Wills, M., & Lever, A. (2018). No evidence of ongoing evolution in replication competent latent HIV-1 in a patient followed up for two years.. Sci Rep, 8 (1), 2639. https://doi.org/10.1038/s41598-018-20682-w
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.
Keywords
CD4-Positive T-Lymphocytes, Humans, HIV-1, HIV Infections, Viral Load, Evolution, Molecular, Virus Latency, Virus Replication, Middle Aged, Male
Sponsorship
Medical Research Council (MR/M003515/1)
Academy of Medical Sciences (unknown)
NIHR Clinical Research Network Eastern (via Cambridge University Hospitals NHS Foundation Trust (CUH)) (CRN Core Allocation 2014/15 Di)
British HIV Association (BHIVA) (unknown)
Medical Research Council (MR/N02043X/1)
Identifiers
External DOI: https://doi.org/10.1038/s41598-018-20682-w
This record's URL: https://www.repository.cam.ac.uk/handle/1810/275393
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