Cocaine enhances HIV-1 replication in CD4+ T cells by down-regulating MiR-125b.
The main objective of this study was to examine effects of cocaine on HIV-1 replication in primary CD4+ T cells. Cocaine a commonly used drug among HIV-1 positive individuals serves as a cofactor for HIV-1 infection and progression to acquired immunodeficiency syndrome (AIDS). Accumulating evidence...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3520918?pdf=render |
| _version_ | 1811288841772859392 |
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| author | Chinmay K Mantri Jui Pandhare Dash Jyoti Velamarti Mantri Chandravanu C V Dash |
| author_facet | Chinmay K Mantri Jui Pandhare Dash Jyoti Velamarti Mantri Chandravanu C V Dash |
| author_sort | Chinmay K Mantri |
| collection | DOAJ |
| description | The main objective of this study was to examine effects of cocaine on HIV-1 replication in primary CD4+ T cells. Cocaine a commonly used drug among HIV-1 positive individuals serves as a cofactor for HIV-1 infection and progression to acquired immunodeficiency syndrome (AIDS). Accumulating evidence suggest that cocaine increases HIV-1 replication in cell cultures, peripheral blood mononuclear cells (PBMCs) and animal models. Intriguingly, there are no studies on cocaine-induced alterations in HIV-1 replication in primary CD4+ T cells that serve as the main targets for HIV-1 replication in vivo. In this report, we demonstrate cocaine-induced enhancement of HIV-1 replication in primary CD4+ T cells isolated from human PBMCs. To decipher a potential mechanism, we examined whether cocaine targets the innate antiviral immunity of CD4+ T cells mediated by cellular microRNAs (miRNAs). This is because recently a network of anti-HIV miRNAs in CD4+ T cells is highlighted to suppress viral replication. Our genome wide miRNA expression analysis indicated downregulation of several anti-HIV miRNAs (miR-28, miR-125b, miR-150, miR-223, and miR-382) in cocaine treated CD4+ T cells. However, our real-time quantitative PCR analysis revealed significant downregulation of miR-125b only. Our results illustrated that miR-125b knockdown enhances HIV-1 replication, whereas overexpression of miR-125b decreases HIV-1 replication in these cells. Therefore, we believe miR-125b is a key player for the cocaine induced enhancement of HIV-1 replication in CD4+ T cells. Since, miR-125b targets the 3' UTR regions of HIV-1 transcripts and inhibits viral protein translation, our data suggest modulation of post entry steps of HIV-1 by cocaine. Given that a plethora of studies suggest that cocaine regulates HIV entry, our results implicate a potentially novel mechanism by which cocaine can increase viral replication in CD4+ T cells. |
| first_indexed | 2024-04-13T03:44:24Z |
| format | Article |
| id | doaj.art-32ff3030c07445bf8f9a2bbdf21770aa |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T03:44:24Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-32ff3030c07445bf8f9a2bbdf21770aa2022-12-22T03:04:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01712e5138710.1371/journal.pone.0051387Cocaine enhances HIV-1 replication in CD4+ T cells by down-regulating MiR-125b.Chinmay K MantriJui Pandhare DashJyoti Velamarti MantriChandravanu C V DashThe main objective of this study was to examine effects of cocaine on HIV-1 replication in primary CD4+ T cells. Cocaine a commonly used drug among HIV-1 positive individuals serves as a cofactor for HIV-1 infection and progression to acquired immunodeficiency syndrome (AIDS). Accumulating evidence suggest that cocaine increases HIV-1 replication in cell cultures, peripheral blood mononuclear cells (PBMCs) and animal models. Intriguingly, there are no studies on cocaine-induced alterations in HIV-1 replication in primary CD4+ T cells that serve as the main targets for HIV-1 replication in vivo. In this report, we demonstrate cocaine-induced enhancement of HIV-1 replication in primary CD4+ T cells isolated from human PBMCs. To decipher a potential mechanism, we examined whether cocaine targets the innate antiviral immunity of CD4+ T cells mediated by cellular microRNAs (miRNAs). This is because recently a network of anti-HIV miRNAs in CD4+ T cells is highlighted to suppress viral replication. Our genome wide miRNA expression analysis indicated downregulation of several anti-HIV miRNAs (miR-28, miR-125b, miR-150, miR-223, and miR-382) in cocaine treated CD4+ T cells. However, our real-time quantitative PCR analysis revealed significant downregulation of miR-125b only. Our results illustrated that miR-125b knockdown enhances HIV-1 replication, whereas overexpression of miR-125b decreases HIV-1 replication in these cells. Therefore, we believe miR-125b is a key player for the cocaine induced enhancement of HIV-1 replication in CD4+ T cells. Since, miR-125b targets the 3' UTR regions of HIV-1 transcripts and inhibits viral protein translation, our data suggest modulation of post entry steps of HIV-1 by cocaine. Given that a plethora of studies suggest that cocaine regulates HIV entry, our results implicate a potentially novel mechanism by which cocaine can increase viral replication in CD4+ T cells.http://europepmc.org/articles/PMC3520918?pdf=render |
| spellingShingle | Chinmay K Mantri Jui Pandhare Dash Jyoti Velamarti Mantri Chandravanu C V Dash Cocaine enhances HIV-1 replication in CD4+ T cells by down-regulating MiR-125b. PLoS ONE |
| title | Cocaine enhances HIV-1 replication in CD4+ T cells by down-regulating MiR-125b. |
| title_full | Cocaine enhances HIV-1 replication in CD4+ T cells by down-regulating MiR-125b. |
| title_fullStr | Cocaine enhances HIV-1 replication in CD4+ T cells by down-regulating MiR-125b. |
| title_full_unstemmed | Cocaine enhances HIV-1 replication in CD4+ T cells by down-regulating MiR-125b. |
| title_short | Cocaine enhances HIV-1 replication in CD4+ T cells by down-regulating MiR-125b. |
| title_sort | cocaine enhances hiv 1 replication in cd4 t cells by down regulating mir 125b |
| url | http://europepmc.org/articles/PMC3520918?pdf=render |
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