dc.contributor.author | Bernard, Mark A. | en_US |
dc.contributor.author | Zhao, Hui | en_US |
dc.contributor.author | Yue, Simon C. | en_US |
dc.contributor.author | Anandaiah, Asha | en_US |
dc.contributor.author | Koziel, Henry | en_US |
dc.contributor.author | Tachado, Souvenir D. | en_US |
dc.date.accessioned | 2014-10-01T14:28:41Z | |
dc.date.issued | 2014 | en_US |
dc.identifier.citation | Bernard, Mark A., Hui Zhao, Simon C. Yue, Asha Anandaiah, Henry Koziel, and Souvenir D. Tachado. 2014. “Novel HIV-1 MiRNAs Stimulate TNFα Release in Human Macrophages via TLR8 Signaling Pathway.” PLoS ONE 9 (9): e106006. doi:10.1371/journal.pone.0106006. http://dx.doi.org/10.1371/journal.pone.0106006. | en |
dc.identifier.issn | 1932-6203 | en |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:12987304 | |
dc.description.abstract | Purpose 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. | en |
dc.language.iso | en_US | en |
dc.publisher | Public Library of Science | en |
dc.relation.isversionof | doi:10.1371/journal.pone.0106006 | en |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4156304/pdf/ | en |
dash.license | LAA | en_US |
dc.subject | Biology and life sciences | en |
dc.subject | Biochemistry | en |
dc.subject | DNA | en |
dc.subject | DNA amplification | en |
dc.subject | RNA | en |
dc.subject | Messenger RNA | en |
dc.subject | MicroRNAs | en |
dc.subject | Small interfering RNAs | en |
dc.subject | Cell Biology | en |
dc.subject | Cellular Types | en |
dc.subject | Animal Cells | en |
dc.subject | Blood Cells | en |
dc.subject | White Blood Cells | en |
dc.subject | Macrophages | en |
dc.subject | Immune Cells | en |
dc.subject | Immunology | en |
dc.subject | Clinical Immunology | en |
dc.subject | Immunopathology | en |
dc.subject | Immune Response | en |
dc.subject | Inflammation | en |
dc.subject | Microbiology | en |
dc.subject | Medical Microbiology | en |
dc.subject | Microbial Pathogens | en |
dc.subject | Viral Pathogens | en |
dc.subject | Immunodeficiency Viruses | en |
dc.subject | HIV-1 | en |
dc.subject | Organisms | en |
dc.subject | Viruses | en |
dc.title | Novel HIV-1 MiRNAs Stimulate TNFα Release in Human Macrophages via TLR8 Signaling Pathway | en |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en |
dc.relation.journal | PLoS ONE | en |
dash.depositing.author | Zhao, Hui | en_US |
dc.date.available | 2014-10-01T14:28:41Z | |
dc.identifier.doi | 10.1371/journal.pone.0106006 | * |
dash.contributor.affiliated | Anandaiah, Asha | |
dash.contributor.affiliated | Zhao, Hui | |