Acute-Phase CD8 T cell responses that select for escape variants are needed to control live attenuated simian immunodeficiency virus

Harris, M., Burns, C., Becker, E., Braasch, A., Gostick, Emma, Johnson, R., Broman, K., Price, David ORCID: https://orcid.org/0000-0001-9416-2737, Friedrich, T. and O'Connor, S. 2013. Acute-Phase CD8 T cell responses that select for escape variants are needed to control live attenuated simian immunodeficiency virus. Journal of Virology 87 (16) , pp. 9353-9364. 10.1128/JVI.00909-13

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Abstract

The overall CD8 T cell response to human/simian immunodeficiency virus (HIV/SIV) targets a collection of discrete epitope specificities. Some of these epitope-specific CD8 T cells emerge in the weeks and months following infection and rapidly select forsequence variants, whereas other CD8 T cell responses develop during the chronic infection phase and rarely select for sequence variants. In this study, we tested the hypothesis that acute-phase CD8 T cell responses that do not rapidly select for escapevariants are unable to control viral replication in vivo as well as those that do rapidly select for escape variants. We created a derivative of live attenuated SIV (SIVmac239Δnef) in which we ablated five epitopes that elicit early CD8 T cell responses and rapidly accumulate sequence variants in SIVmac239-infected Mauritian cynomolgus macaques (MCMs) that are homozygous for the M3 major histocompatibility complex (MHC) haplotype. This live attenuated SIV variant was called m3KOΔnef. Viremia was significantly higher in M3 homozygous MCMs infected withm3KOΔnef than in either MHC-mismatched MCMs infected with m3KOΔ nef or MCMs infected with SIVmac239Δnef. Three CD8 T cell responses, including two that do not rapidly select for escape variants, predominated during earlym3KOΔnef infection in the M3 homozygous MCMs, but these animals were unable to control viral replication. These re-sults provide evidence that acute-phase CD8 T cell responses that have the potential to rapidly select for escape variants in the early phase ofinfection are needed to establish viral control in vivo.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General) R Medicine > RZ Other systems of medicine
Uncontrolled Keywords:	Animals; CD8-Positive T-Lymphocytes; Genetic Variation; Immune Evasion; Macaca; Selection, Genetic; Simian Acquired Immunodeficiency Syndrome; Simian immunodeficiency virus; Viremia
Publisher:	American Society for Microbiology
ISSN:	0022-538X
Date of First Compliant Deposit:	6 September 2017
Last Modified:	05 May 2023 00:09
URI:	https://orca.cardiff.ac.uk/id/eprint/87908

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