Can Non-lytic CD8+ T Cells Drive HIV-1 Escape?
Al Basatena NKS, Chatzimichalis K, Graw F, Frost SDW, Regoes RR, Asquith B (2013)
Publication Type: Journal article
Publication year: 2013
Journal
Book Volume: 9
Article Number: e1003656
Journal Issue: 11
DOI: 10.1371/journal.ppat.1003656
Abstract
The CD8+ T cell effector mechanisms that mediate control of HIV-1 and SIV infections remain poorly understood. Recent work suggests that the mechanism may be primarily non-lytic. This is in apparent conflict with the observation that SIV and HIV-1 variants that escape CD8+ T cell surveillance are frequently selected. Whilst it is clear that a variant that has escaped a lytic response can have a fitness advantage compared to the wild-type, it is less obvious that this holds in the face of non-lytic control where both wild-type and variant infected cells would be affected by soluble factors. In particular, the high motility of T cells in lymphoid tissue would be expected to rapidly destroy local effects making selection of escape variants by non-lytic responses unlikely. The observation of frequent HIV-1 and SIV escape poses a number of questions. Most importantly, is the consistent observation of viral escape proof that HIV-1- and SIV-specific CD8+ T cells lyse infected cells or can this also be the result of non-lytic control? Additionally, the rate at which a variant strain escapes a lytic CD8+ T cell response is related to the strength of the response. Is the same relationship true for a non-lytic response? Finally, the potential anti-viral control mediated by non-lytic mechanisms compared to lytic mechanisms is unknown. These questions cannot be addressed with current experimental techniques nor with the standard mathematical models. Instead we have developed a 3D cellular automaton model of HIV-1 which captures spatial and temporal dynamics. The model reproduces in vivo HIV-1 dynamics at the cellular and population level. Using this model we demonstrate that non-lytic effector mechanisms can select for escape variants but that outgrowth of the variant is slower and less frequent than from a lytic response so that non-lytic responses can potentially offer more durable control.
Authors with CRIS profile
Involved external institutions
Imperial College London / The Imperial College of Science, Technology and Medicine
United Kingdom (GB)
Birkbeck, University of London
United Kingdom (GB)
Los Alamos National Laboratory
United States (USA) (US)
University of Cambridge
United Kingdom (GB)
Eidgenössische Technische Hochschule Zürich (ETHZ) / Swiss Federal Institute of Technology in Zurich
Switzerland (CH)
United Kingdom (GB)
Birkbeck, University of London
United Kingdom (GB)
Los Alamos National Laboratory
United States (USA) (US)
University of Cambridge
United Kingdom (GB)
Eidgenössische Technische Hochschule Zürich (ETHZ) / Swiss Federal Institute of Technology in Zurich
Switzerland (CH)
How to cite
APA:
Al Basatena, N.-K.S., Chatzimichalis, K., Graw, F., Frost, S.D.W., Regoes, R.R., & Asquith, B. (2013). Can Non-lytic CD8+ T Cells Drive HIV-1 Escape? PLoS Pathogens, 9(11). https://doi.org/10.1371/journal.ppat.1003656
MLA:
Al Basatena, Nafisa-Katrin Seich, et al. "Can Non-lytic CD8+ T Cells Drive HIV-1 Escape?" PLoS Pathogens 9.11 (2013).
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