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dc.creatorGarcia-Knight, MA
dc.creatorSlyker, J
dc.creatorPayne, BL
dc.creatorPond, SLK
dc.creatorDe Silva, TI
dc.creatorChohan, B
dc.creatorKhasimwa, B
dc.creatorMbori-Ngacha, D
dc.creatorJohn-Stewart, G
dc.creatorRowland-Jones, SL
dc.creatorEsbjörnsson, J
dc.date.accessioned2021-01-26T20:37:15Z
dc.date.available2021-01-26T20:37:15Z
dc.date.issued2016-07-12
dc.identifier.issn2045-2322
dc.identifier.issn2045-2322
dc.identifier.doihttp://dx.doi.org/10.34944/dspace/5021
dc.identifier.other27403940 (pubmed)
dc.identifier.urihttp://hdl.handle.net/20.500.12613/5039
dc.description.abstractAntiretroviral therapy-naive HIV-1 infected infants experience poor viral containment and rapid disease progression compared to adults. Viral factors (e.g. transmitted cytotoxic T- lymphocyte (CTL) escape mutations) or infant factors (e.g. reduced CTL functional capacity) may explain this observation. We assessed CTL functionality by analysing selection in CTL-targeted HIV-1 epitopes following perinatal infection. HIV-1 gag, pol and nef sequences were generated from a historical repository of longitudinal specimens from 19 vertically infected infants. Evolutionary rate and selection were estimated for each gene and in CTL-restricted and non-restricted epitopes. Evolutionary rate was higher in nef and gag vs. pol, and lower in infants with non-severe immunosuppression vs. severe immunosuppression across gag and nef. Selection pressure was stronger in infants with non-severe immunosuppression vs. severe immunosuppression across gag. The analysis also showed that infants with non-severe immunosuppression had stronger selection in CTL-restricted vs. non-restricted epitopes in gag and nef. Evidence of stronger CTL selection was absent in infants with severe immunosuppression. These data indicate that infant CTLs can exert selection pressure on gag and nef epitopes in early infection and that stronger selection across CTL epitopes is associated with favourable clinical outcomes. These results have implications for the development of paediatric HIV-1 vaccines.
dc.format.extent29536-
dc.language.isoen
dc.relation.haspartScientific Reports
dc.relation.isreferencedbySpringer Science and Business Media LLC
dc.rightsCC BY
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectChild, Preschool
dc.subjectDisease Progression
dc.subjectEvolution, Molecular
dc.subjectFemale
dc.subjectGenes, gag
dc.subjectGenes, pol
dc.subjectHIV Infections
dc.subjectHIV-1
dc.subjectHumans
dc.subjectInfant
dc.subjectT-Lymphocytes, Cytotoxic
dc.subjectnef Gene Products, Human Immunodeficiency Virus
dc.titleViral Evolution and Cytotoxic T Cell Restricted Selection in Acute Infant HIV-1 Infection
dc.typeArticle
dc.type.genreJournal Article
dc.relation.doi10.1038/srep29536
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
dc.creator.orcidPond, Sergei L. Kosakovsky|0000-0003-4817-4029
dc.date.updated2021-01-26T20:37:11Z
refterms.dateFOA2021-01-26T20:37:15Z


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