Lustig, Gila;
Ganga, Yashica;
Rodel, Hylton E;
Tegally, Houriiyah;
Khairallah, Afrah;
Jackson, Laurelle;
Cele, Sandile;
... Sigal, Alex; + view all
(2024)
SARS-CoV-2 infection in immunosuppression evolves sub-lineages which independently accumulate neutralization escape mutations.
Virus Evolution
, 10
(1)
, Article vead075. 10.1093/ve/vead075.
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Abstract
One mechanism of variant formation may be evolution during long-term infection in immunosuppressed people. To understand the viral phenotypes evolved during such infection, we tested SARS-CoV-2 viruses evolved from an ancestral B.1 lineage infection lasting over 190 days post-diagnosis in an advanced HIV disease immunosuppressed individual. Sequence and phylogenetic analysis showed two evolving sub-lineages, with the second sub-lineage replacing the first sub-lineage in a seeming evolutionary sweep. Each sub-lineage independently evolved escape from neutralizing antibodies. The most evolved virus for the first sub-lineage (isolated day 34) and the second sub-lineage (isolated day 190) showed similar escape from ancestral SARS-CoV-2 and Delta-variant infection elicited neutralizing immunity despite having no spike mutations in common relative to the B.1 lineage. The day 190 isolate also evolved higher cell-cell fusion and faster viral replication and caused more cell death relative to virus isolated soon after diagnosis, though cell death was similar to day 34 first sub-lineage virus. These data show that SARS-CoV-2 strains in prolonged infection in a single individual can follow independent evolutionary trajectories which lead to neutralization escape and other changes in viral properties.
| Type: | Article |
|---|---|
| Title: | SARS-CoV-2 infection in immunosuppression evolves sub-lineages which independently accumulate neutralization escape mutations |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/ve/vead075 |
| Publisher version: | http://dx.doi.org/10.1093/ve/vead075 |
| Language: | English |
| Additional information: | © The Author(s) 2024. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Virology, SARS-CoV-2 evolution, advanced HIV disease, immunosuppression, prolonged infection, variants of concern, REPLICATION |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10187847 |
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