Restriction Factor Expression in Vertically Infected Children Living With HIV-1

Area of Science:

• Immunology
• Virology
• Pediatrics

Background:

• 1.7 million children globally live with HIV-1, with 160,000 new infant infections annually.
• Infants have immature adaptive immunity, making innate immunity critical against HIV-1.
• Host restriction factors inhibit HIV-1 replication in vitro, but their in vivo role in children is understudied.

Purpose of the Study:

• To investigate the expression of host restriction factors in children living with HIV-1.
• To determine if restriction factor expression correlates with HIV-1 disease progression in children.

Main Methods:

• Gene expression of restriction factors (APOBEC3A/C/G/H, SAMHD1, ISG15, CDKN1A, MX2, TRIM5, SLFN11) was analyzed using qPCR in CD4+ T cells from 121 vertically infected children.
• Cell surface expression of BST-2/tetherin and T-cell activation markers were assessed by flow cytometry.

Main Results:

• BST-2/tetherin expression on CD4+ T cells positively correlated with viral load and T-cell activation, and negatively with CD4+ T-cell counts.
• SAMHD1 expression showed a negative correlation with T-cell activation markers.
• These correlations were adjusted for gender and age.

Conclusions:

• Certain restriction factors, like BST-2/tetherin and SAMHD1, play a significant role in HIV-1 pathogenesis in children.
• Understanding these factors could inform therapeutic strategies for pediatric HIV-1 infection.