Abstract
Abstract
Background
The interaction between HIV-1 and host immune cells, particularly macrophages, is crucial in understanding viral persistence and pathogenesis. This study aims to explore the impact of HIV-1 infection on macrophage microRNA (miRNA) expression profiles using a systems biology approach to uncover the potential role of miRNAs in modulating macrophage functionality and identify key miRNA targets that may serve as therapeutic avenues.
Methods
PMA-differentiated THP-1 cells were used to model macrophage infection with HIV-1. A custom miRNA microarray was performed to identify dysregulated miRNAs following infection. miRTarBase was utilized for miRNA target identification, revealing gene targets associated with the dysregulated miRNAs. A protein-protein interaction (PPI) map of miRNA targets and their first interactors was constructed, with key nodes identified based on a calculated disease score, which considered degree, betweenness centrality, average shortest path length, and clustering coefficient. Gene Ontology molecular function analysis was also conducted on the identified targets.
Results
The miRNA microarray identified 23 dysregulated miRNAs in HIV-1-infected macrophages, with 8 upregulated and 15 downregulated. Among these, the top 10 dysregulated miRNAs targeted over 2000 unique genes. PPI analysis revealed key nodes in the upregulated miRNA network, including
APP
,
MYC
,
ESR2
,
RAF1
, and
HIST1H4A
, while
ZRANB1
,
HSPA8
,
TGOLN2
,
HSPA5
, and
BRD4
were prominent in the downregulated miRNA network. Notably,
KRAS
,
CUL3
,
TP53
,
ESR1
, and
PARP1
were influenced by both upregulated and downregulated miRNAs. Gene Ontology analysis indicated that the targeted genes were involved in processes such as protein and RNA binding, ATPase activity, and ribosomal function.
Conclusions
HIV-1 infection induces significant dysregulation of miRNAs in macrophages, impacting a wide array of gene targets and molecular functions. These findings suggest that miRNA-mediated regulation may play a crucial role in HIV-1 pathogenesis within macrophages and present potential targets for miRNA-based therapeutic strategies.