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Restriction Factor Expression in Vertically Infected Children Living With HIV-1
Martin Bortlik1,2,3, Dennis C Copertino4, Phillip M Brailey1,5,6
1From the Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, DC.
Insights
Host restriction factors are crucial for innate immunity in children with HIV-1. Their expression correlates with viral load and immune activation, suggesting a role in disease progression.
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.
Introduction:
Around 1.7 million children are estimated to live with HIV-1 worldwide, and about 160,000 infants are newly infected every year. Since adaptive immunity takes time to mature and develop in infants, and maternal antibodies provide limited antiviral activity, innate and intrinsic immunity against HIV-1 in the young is of critical importance. Intrinsic restriction factors are cellular proteins that effectively inhibit HIV-1 replication in vitro, but there is limited understanding of their role in vivo, and little to no data has been reported on the expression of host restriction factors in children. We hypothesized that restriction factor expression might be particularly important in children living with HIV-1 and correlate with disease progression.
Methods:
We analyzed gene expression of APOBEC3A, APOBEC3C, APOBEC3G, APOBEC3H, SAMHD1, ISG15, CDKN1A, MX2, TRIM5, and SLFN11 by qPCR in 121 samples of CD4+ T cells from vertically infected children living with HIV-1. Cell surface expression of BST-2/tetherin and markers of CD4+ T-cell activation were analyzed by flow cytometry.
Results:
After adjusting for gender and age, BST-2/tetherin expression on CD4+ T cells showed significant positive correlation with viral load (P = 0.0006; ρ = 0.33), CD4+ T-cell activation (P < 0.0001; ρ = 0.53), CD8+ T-cell activation (P < 0.0001; ρ = 0.53), and a negative correlation with CD4+ T-cell counts (P = 0.0008; ρ = -0.33). The expression of SAMHD1 correlated negatively with markers of T-cell activation (P = 0.046; ρ = -0.22).
Discussion:
These results suggest an important role of some restriction factors in the pathogenesis of HIV-1 in children.
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