Vol 9: Novel HIV-1 MiRNAs Stimulate TNF Release in Human Macrophages via TLR8 Signaling Pathway.Report as inadecuate



 Vol 9: Novel HIV-1 MiRNAs Stimulate TNF Release in Human Macrophages via TLR8 Signaling Pathway.


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This article is from PLoS ONE, volume 9.AbstractPurpose: To determine whether HIV-1 produces microRNAs and elucidate whether these miRNAs can induce inflammatory response in macrophages independent of the conventional miRNA function in RNA interference leading to chronic immune activation. Methods: Using sensitive quantitative Real Time RT-PCR and sequencing, we detected novel HIV-derived miRNAs in the sera of HIV+ persons, and associated with exosomes. Release of TNFα by macrophages challenged with HIV miRNAs was measured by ELISA. Results: HIV infection of primary alveolar macrophages produced elevated levels of viral microRNAs vmiR88, vmiR99 and vmiR-TAR in cell extracts and in exosome preparations from conditioned medium. Furthermore, these miRNAs were also detected in exosome fraction of sera from HIV-infected persons. Importantly, vmiR88 and vmiR99 but not vmiR-TAR stimulated human macrophage TNFα release, which is dependent on macrophage TLR8 expression. These data support a potential role for HIV-derived vmiRNAs released from infected macrophages as contributing to chronic immune activation in HIV-infected persons, and may represent a novel therapeutic target to limit AIDS pathogenesis. Conclusion: Novel HIV vmiR88 and vmiR99 are present in the systemic circulation of HIV+ persons and could exhibit biological function independent of gene silencing as ligands for TLR8 signaling that promote macrophage TNFα release, and may contribute to chronic immune activation. Targeting novel HIV-derived miRNAs may represent a therapeutic strategy to limit chronic immune activation and AIDS progression.



Author: Bernard, Mark A.; Zhao, Hui; Yue, Simon C.; Anandaiah, Asha; Koziel, Henry; Tachado, Souvenir D.

Source: https://archive.org/







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