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Viral Evolution and Cytotoxic T Cell Restricted Selection in Acute Infant HIV-1 Infection

Garcia-Knight, MA
; 
Slyker, J
; 
Payne, BL
; 
Pond, SLK
; 
De Silva, TI
; 
Chohan, B
; 
Khasimwa, B
; 
Mbori-Ngacha, D
; 
John-Stewart, G
; 
Rowland-Jones, SL
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Journal Article
Date
2016-07-12
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Department
Subject
Child, Preschool
 Disease Progression
 Evolution, Molecular
 Female
 Genes, gag
 Genes, pol
 HIV Infections
 HIV-1
 Humans
 Infant
 T-Lymphocytes, Cytotoxic
 nef Gene Products, Human Immunodeficiency Virus
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http://hdl.handle.net/20.500.12613/5039
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Viral Evolution and Cytotoxic T Cell Restricted Selection in Acute Infant HIV-1 Infection.pdf
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DOI
10.1038/srep29536
Abstract
Antiretroviral 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.
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Springer Science and Business Media LLC
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Scientific Reports
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