title: Genetic imprint of vaccination on simian/human immunodeficiency virus type 1 transmitted viral genomes in rhesus macaques.
abstract: Understanding the genetic, antigenic and structural changes that occur during HIV-1 infection in response to pre-existing immunity will facilitate current efforts to develop an HIV-1 vaccine. Much is known about HIV-1 variation at the population level but little with regard to specific changes occurring in the envelope glycoprotein within a host in response to immune pressure elicited by antibodies. The aim of this study was to track and map specific early genetic changes occurring in the viral envelope gene following vaccination using a highly controlled viral challenge setting in the SHIV macaque model. We generated 449 full-length env sequences from vaccinees, and 63 from the virus inoculum. Analysis revealed a different pattern in the distribution and frequency of mutations in the regions of the envelope gene targeted by the vaccine as well as different patterns of diversification between animals in the naïve control group and vaccinees. Given the high stringency of the model it is remarkable that we were able to identify genetic changes associated with the vaccination. This work provides insight into the characterization of breakthrough viral populations in less than fully efficacious vaccines and illustrates the value of HIV-1 Env SHIV challenge model in macaques to unravel the mechanisms driving HIV-1 envelope genetic diversity in the presence of vaccine induced-responses.
authors: Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom. Mariana.varela@glasgow.ac.uk
authors: Mariana
authors: M
authors: Varela
authors: Ernst
authors: E
authors: Verschoor
authors: Rachel P J
authors: RP
authors: Lai
authors: Joseph
authors: J
authors: Hughes
authors: Petra
authors: P
authors: Mooj
authors: Trevelyan J
authors: TJ
authors: McKinley
authors: Timothy J
authors: TJ
authors: Fitzmaurice
authors: Lisa
authors: L
authors: Landskron
authors: Brian J
authors: BJ
authors: Willett
authors: Simon D W
authors: SD
authors: Frost
authors: Willy M
authors: WM
authors: Bogers
authors: Jonathan L
authors: JL
authors: Heeney
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D019143:Evolution, Molecular; D016679:Genome, Viral / Q000235:genetics*; D018392:Genomic Imprinting / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology*; D008253:Macaca mulatta; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000276:immunology*; D014611:Vaccination; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D054299:env Gene Products, Human Immunodeficiency Virus
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