Selective expansion of viral variants following experimental transmission of a reconstituted feline immunodeficiency virus quasispecies

Willett, B.J. , Kraase, M., Logan, N., McMonagle, E., Varela, M. and Hosie, M.J. (2013) Selective expansion of viral variants following experimental transmission of a reconstituted feline immunodeficiency virus quasispecies. PLoS ONE, 8(1), e54871. (doi:10.1371/journal.pone.0054871) (PMID:23372784) (PMCID:PMC3553009)

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Abstract

Following long-term infection with virus derived from the pathogenic GL8 molecular clone of feline immunodeficiency virus (FIV), a range of viral variants emerged with distinct modes of interaction with the viral receptors CD134 and CXCR4, and sensitivities to neutralizing antibodies. In order to assess whether this viral diversity would be maintained following subsequent transmission, a synthetic quasispecies was reconstituted comprising molecular clones bearing envs from six viral variants and its replicative capacity compared in vivo with a clonal preparation of the parent virus. Infection with either clonal (Group 1) or diverse (Group 2) challenge viruses, resulted in a reduction in CD4+ lymphocytes and an increase in CD8+ lymphocytes. Proviral loads were similar in both study groups, peaking by 10 weeks post-infection, a higher plateau (set-point) being achieved and maintained in study Group 1. Marked differences in the ability of individual viral variants to replicate were noted in Group 2; those most similar to GL8 achieved higher viral loads while variants such as the chimaeras bearing the B14 and B28 Envs grew less well. The defective replication of these variants was not due to suppression by the humoral immune response as virus neutralising antibodies were not elicited within the study period. Similarly, although potent cellular immune responses were detected against determinants in Env, no qualitative differences were revealed between animals infected with either the clonal or the diverse inocula. However, in vitro studies indicated that the reduced replicative capacity of variants B14 and B28 in vivo was associated with altered interactions between the viruses and the viral receptor and co-receptor. The data suggest that viral variants with GL8-like characteristics have an early, replicative advantage and should provide the focus for future vaccine development.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Hosie, Professor Margaret and Willett, Professor Brian and McMonagle, Mrs Elizabeth and Logan, Miss Nicola and Varela, Dr Mariana
Authors: Willett, B.J., Kraase, M., Logan, N., McMonagle, E., Varela, M., and Hosie, M.J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN:1932-6203
Published Online:23 January 2013
Copyright Holders:Copyright © 2013 The Authors
First Published:First published in PLoS ONE 8(1):e54871
Publisher Policy:Reproduced under a Creative Commons License

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