TY - JOUR
T1 - Correlation between HIV sequence evolution, specific immune response and clinical outcome in vertically infected infants
AU - Halapi, Eva
AU - Leitner, Thomas
AU - Jansson, Marianne
AU - Scarlatti, Gabriella
AU - Orlandi, Paola
AU - Plebani, Anna
AU - Romiti, Luisa
AU - Albert, Jan
AU - Wigzell, Hans
AU - Rossi, Paolo
PY - 1997
Y1 - 1997
N2 - Objective: To evaluate sequence evolution in relation to different rates of disease progression in infants infected with HIV-1. Design: Variability in the gp120 V3 region was analysed in HIV-1-infected children with different clinical courses, slow progression (n = 2) versus progressive disease (n = 3). Methods: Cloning and sequencing of virus-derived DNA from uncultured peripheral blood mononuclear cells was performed at two to three timepoints from birth and up to the fifth year of life. Sequence variability was estimated by calculating the genetic distance and the proportion and ratio of synonymous and non-synonymous nucleotide substitutions over time. Results: Genetic distances were significantly shorter in children with fast progression to disease, a predominance of synonymous nucleotide substitutions also being detected at later timepoints. Conversely, a preferential accumulation of non-synonymous nucleotide substitutions was apparent in children with slow disease progression. Furthermore, a positive correlation between a decreased ratio of synonymous/non-synonymous nucleotide substitutions and the ability of children's sera to react with synthetic peptides representing the autologous virus sequence was determined. Conclusion: Data suggest that an antigenically more diverse virus population emerges in infected children with slower progression to disease as a result of a stronger immune pressure.
AB - Objective: To evaluate sequence evolution in relation to different rates of disease progression in infants infected with HIV-1. Design: Variability in the gp120 V3 region was analysed in HIV-1-infected children with different clinical courses, slow progression (n = 2) versus progressive disease (n = 3). Methods: Cloning and sequencing of virus-derived DNA from uncultured peripheral blood mononuclear cells was performed at two to three timepoints from birth and up to the fifth year of life. Sequence variability was estimated by calculating the genetic distance and the proportion and ratio of synonymous and non-synonymous nucleotide substitutions over time. Results: Genetic distances were significantly shorter in children with fast progression to disease, a predominance of synonymous nucleotide substitutions also being detected at later timepoints. Conversely, a preferential accumulation of non-synonymous nucleotide substitutions was apparent in children with slow disease progression. Furthermore, a positive correlation between a decreased ratio of synonymous/non-synonymous nucleotide substitutions and the ability of children's sera to react with synthetic peptides representing the autologous virus sequence was determined. Conclusion: Data suggest that an antigenically more diverse virus population emerges in infected children with slower progression to disease as a result of a stronger immune pressure.
KW - Disease progression
KW - Genetic variability
KW - gp120 V3 region
KW - Paediatric HIV-1 infection
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U2 - 10.1097/00002030-199714000-00007
DO - 10.1097/00002030-199714000-00007
M3 - Article
C2 - 9386805
AN - SCOPUS:9844229369
VL - 11
SP - 1709
EP - 1717
JO - AIDS
JF - AIDS
SN - 0269-9370
IS - 14
ER -