Genetic imprint of vaccination on simian/human immunodeficiency virus type 1 transmitted viral genomes in rhesus macaques. 2013

Mariana Varela, and Ernst Verschoor, and Rachel P J Lai, and Joseph Hughes, and Petra Mooj, and Trevelyan J McKinley, and Timothy J Fitzmaurice, and Lisa Landskron, and Brian J Willett, and Simon D W Frost, and Willy M Bogers, and Jonathan L Heeney
Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom. Mariana.varela@glasgow.ac.uk

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.

UI MeSH Term Description Entries
D008253 Macaca mulatta A species of the genus MACACA inhabiting India, China, and other parts of Asia. The species is used extensively in biomedical research and adapts very well to living with humans. Chinese Rhesus Macaques,Macaca mulatta lasiota,Monkey, Rhesus,Rhesus Monkey,Rhesus Macaque,Chinese Rhesus Macaque,Macaca mulatta lasiotas,Macaque, Rhesus,Rhesus Macaque, Chinese,Rhesus Macaques,Rhesus Macaques, Chinese,Rhesus Monkeys
D000704 Analysis of Variance A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable. ANOVA,Analysis, Variance,Variance Analysis,Analyses, Variance,Variance Analyses
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014611 Vaccination Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. Immunization, Active,Active Immunization,Active Immunizations,Immunizations, Active,Vaccinations
D015302 Simian Immunodeficiency Virus Species of the genus LENTIVIRUS, subgenus primate immunodeficiency viruses (IMMUNODEFICIENCY VIRUSES, PRIMATE), that induces acquired immunodeficiency syndrome in monkeys and apes (SAIDS). The genetic organization of SIV is virtually identical to HIV. SIV (Simian immunodeficiency virus),Immunodeficiency Viruses, Simian,Simian Immunodeficiency Viruses,Immunodeficiency Virus, Simian
D015497 HIV-1 The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte. Human immunodeficiency virus 1,HIV-I,Human Immunodeficiency Virus Type 1,Immunodeficiency Virus Type 1, Human
D016679 Genome, Viral The complete genetic complement contained in a DNA or RNA molecule in a virus. Viral Genome,Genomes, Viral,Viral Genomes
D054299 env Gene Products, Human Immunodeficiency Virus Proteins encoded by the ENV GENE of the HUMAN IMMUNODEFICIENCY VIRUS. env Gene Products, HIV,env Proteins, Human Immunodeficiency Virus,envelope Proteins, Human Immunodeficiency Virus
D018392 Genomic Imprinting The variable phenotypic expression of a GENE depending on whether it is of paternal or maternal origin, which is a function of the DNA METHYLATION pattern. Imprinted regions are observed to be more methylated and less transcriptionally active. (Segen, Dictionary of Modern Medicine, 1992) Genetic Imprinting,Parental Imprinting,Imprinting, Genetic,Imprinting, Genomic,Imprinting, Parental
D019143 Evolution, Molecular The process of cumulative change at the level of DNA; RNA; and PROTEINS, over successive generations. Molecular Evolution,Genetic Evolution,Evolution, Genetic

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