Abstract

HIV-exposed uninfected (HEU) infants are disproportionately at a higher risk of morbidity and mortality, as compared to HIV-unexposed uninfected (HUU) infants. Here, we used transcriptional profiling of peripheral blood mononuclear cells to determine immunological signatures of in utero HIV exposure. We identified 262 differentially expressed genes (DEGs) in HEU compared to HUU infants. Weighted gene co-expression network analysis (WGCNA) identified six modules that had significant associations with clinical traits. Functional enrichment analysis on both DEGs and the six significantly associated modules revealed an enrichment of G-protein coupled receptors and the immune system, specifically affecting neutrophil function and antibacterial responses. Additionally, malaria pathogenicity genes (thrombospondin 1-(THBS 1), interleukin 6 (IL6), and arginine decarboxylase 2 (ADC2)) were down-regulated. Of interest, the down-regulated immunity genes were positively correlated to the expression of epigenetic factors of the histone family and high-mobility group protein B2 (HMGB2), suggesting their role in the dysregulation of the HEU transcriptional landscape. Overall, we show that genes primarily associated with neutrophil mediated immunity were repressed in the HEU infants. Our results suggest that this could be a contributing factor to the increased susceptibility to bacterial infections associated with higher morbidity and mortality commonly reported in HEU infants.

Details

Title
Peripheral blood mononuclear cell transcriptomes reveal an over-representation of down-regulated genes associated with immunity in HIV-exposed uninfected infants
Author
Musimbi, Zaneta D 1 ; Rono, Martin K 2   VIAFID ORCID Logo  ; Otieno, James R 3   VIAFID ORCID Logo  ; Nelson Kibinge 3 ; Ochola-Oyier, Lynette Isabella 2 ; de Villiers, Etienne Pierre 4   VIAFID ORCID Logo  ; Nduati, Eunice W 2 

 Center of Biotechnology and Bioinformatics, Chiromo Campus, University of Nairobi, Nairobi, Kenya 
 KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya; Pwani University Biotechnology Research Centre, Pwani University, Kilifi, Kenya 
 KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya 
 KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya; Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK 
Pages
1-12
Publication year
2019
Publication date
Dec 2019
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2321202042
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.