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

Area of Science:

• Immunology
• Virology
• Evolutionary Biology

Background:

• Infants with HIV-1 infection show poorer viral control and faster disease progression than adults.
• Factors like transmitted drug resistance, viral mutations, and infant immune capacity may contribute to these differences.

Purpose of the Study:

• To investigate cytotoxic T-lymphocyte (CTL) functionality in vertically infected infants by analyzing selection pressures on HIV-1 epitopes.
• To determine if infant CTL responses influence early viral evolution and clinical outcomes.

Main Methods:

• Longitudinal HIV-1 gag, pol, and nef sequences were analyzed from 19 vertically infected infants.
• Evolutionary rates and selection pressures were estimated for viral genes and CTL-restricted/non-restricted epitopes.
• Selection was compared between infants with severe and non-severe immunosuppression.

Main Results:

• Higher evolutionary rates were observed in nef and gag compared to pol.
• Infants with non-severe immunosuppression exhibited lower evolutionary rates and stronger selection pressure across gag and nef.
• Stronger selection in CTL-restricted epitopes within gag and nef was evident in infants with non-severe immunosuppression, but absent in those with severe immunosuppression.

Conclusions:

• Infant CTLs exert selection pressure on HIV-1 gag and nef epitopes during early infection.
• Stronger CTL selection is associated with more favorable clinical outcomes in infants.
• Findings have implications for developing pediatric HIV-1 vaccines targeting CTL responses.