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Published on: July 6, 2013
Evolution of human immunodeficiency virus type 1 in perinatally infected infants with rapid and slow progression to
F Salvatori1, S Masiero, C Giaquinto
1Department of Oncology and Surgical Sciences, AIDS Reference Center, University of Padova, Italy.
Insights
The origin of human immunodeficiency virus type 1 (HIV-1) infection in infants is linked to a single variant. Host immune pressure, particularly on the V3 region, influences viral evolution and disease progression over time.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Perinatally infected infants often experience varying disease progression rates.
- Understanding the initial viral variants and their evolution is crucial for predicting outcomes.
Purpose of the Study:
- To investigate the relationship between the origin and evolution of human immunodeficiency virus type 1 (HIV-1) variants and disease progression in perinatally infected infants.
- To analyze the V3 region of HIV-1 variants to understand early viral dynamics and host immune selective pressures.
Main Methods:
- Phylogenetic analysis of V3 sequences from mother-infant pairs.
- Sequential sampling of viral variants from infected infants over the first year of life.
- Quantification of plasma HIV-1 RNA levels and analysis of synonymous/nonsynonymous substitutions.
Main Results:
- A single HIV-1 variant initiated infection in all infants, regardless of disease progression speed.
- Viral load initially increased then declined in slow progressors within the first six months.
- Increased nonsynonymous substitutions in the second half of the year in slow progressors suggest stronger host selective pressure.
Conclusions:
- The initial HIV-1 variant determines infection trajectory.
- Host immune response to V3 may regulate viral levels later in life but is unlikely to drive early viral decline.
- Differential selective pressures on viral evolution correlate with disease progression rates.
Abstract:
We addressed the relationship between the origin and evolution of human immunodeficiency virus type 1 (HIV-1) variants and disease outcome in perinatally infected infants by studying the V3 regions of viral variants in samples obtained from five transmitting mothers at delivery and obtained sequentially over the first year of life from their infected infants, two of whom (rapid progressors) rapidly progressed to having AIDS. Phylogenetic analyses disclosed that the V3 sequences from each mother-infant pair clustered together and were clearly distinct from those of the other pairs. Within each pair, the child's sequences formed a monophyletic group, indicating that a single variant initiated the infection in both rapid and slow progressors. Plasma HIV-1 RNA levels increased in all five infants during their first months of life and then declined within the first semester of life only in the three slow progressors. V3 variability increased over time in all infants, but no differences in the pattern of V3 evolution in terms of potential viral phenotype were observed. The numbers of synonymous and nonsynonymous substitutions varied during the first semester of life regardless of viral load, CD4+-cell count, and disease progression. Conversely, during the second semester of life the rate of nonsynonymous substitutions was higher than that of synonymous substitutions in the slow progressors but not in the rapid progressors, thus suggesting a stronger host selective pressure in the former. In view of the proposal that V3 genetic evolution is driven mainly by host immune constraints, these findings suggest that while the immune response to V3 might contribute to regulating viral levels after the first semester of life, it is unlikely to play a determinant role in the initial viral decline soon after birth.
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