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Differential expression of microRNAs in productively HIV-1 infected and bystander macrophages in culture.

ABSTRACT: Macrophages are heterogeneous immune cells with distinct origins, phenotypes, functions and tissue localization. Their susceptibility to HIV-1 is subject to variations from permissiveness to resistance, owing in part to regulatory microRNAs. Here, we used RNAseq to examine the expression of >400 microRNAs in productively infected and bystander cells of HIV-1-exposed macrophage cultures. Two micro-RNAs up regulated in bystander macrophages, miR-221 and miR-222, were identified as negative regulators of CD4 expression and CD4-mediated HIV-1 entry. Both microRNAs were enhanced by TNF-α, an inhibitor of CD4 expression. MiR-221/miR-222 inhibitors recovered HIV-1 entry in TNF-α-treated macrophages by enhancing CD4 expression, and increased HIV-1 replication and spread in macrophages by countering TNF-α-enhanced miR-221/miR-222 expression in bystander cells. In line with these findings, HIV-1-resistant intestinal myeloid cells express higher levels of miR-221 than peripheral blood monocytes. Thus, miR-221/miR-222 act as effectors of the antiviral host response activated during macrophage infection that restrict HIV-1 entry.

ORGANISM(S): Homo sapiens

PROVIDER: GSE103394 | GEO | 2017/09/11

SECONDARY ACCESSION(S): PRJNA401712

REPOSITORIES: GEO

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