miR-150-mediated increase in glucose uptake in HIV-infected cells.

Replication of HIV-1 inside host cells is dependent on both viral and host factors. MicroRNAs are small noncoding RNAs that regulate protein synthesis. MicroRNAs may control viral replication either by directly targeting the viral genome or indirectly through cellular proteins that are required during the viral lifecycle. HIV infection may, in turn, regulate host microRNA expression to facilitate its propagation inside cells. miR-150 has been reported to be an essential factor involved in T-cell activation and may serve as a biomarker for HIV disease progression. The current study provides valuable insights into the role of miR-150 in HIV infection. We quantified miR-150 expression in HIV-infected Jurkat cells and observed a time-dependent increase in the expression of miR-150. In addition, HIV infection led to an enhanced influx of glucose inside the infected cells, which further increased on overexpression of miR-150. The increased uptake of glucose was due to miR-150-mediated increase in expression of glucose transporter-1 (GLUT1). In an attempt to decipher the mechanism, we identified that HIV Tat protein enhanced the expression of miR-150 which then upregulated GLUT1 in HIV-infected cells. In summary, this study sheds light on the role of miR-150 in HIV infection and paves the way for miR-150 as a novel therapeutic target against HIV-1.

G protein-coupled and ATP-sensitive inwardly rectifying potassium ion channels are essential for HIV entry.

The high genetic diversity of Human Immunodeficiency virus (HIV), has hindered the development of effective vaccines or antiviral drugs against it. Hence, there is a continuous need for identification of new antiviral targets. HIV exploits specific host proteins also known as HIV-dependency factors during its replication inside the cell. Potassium channels play a crucial role in the life cycle of several viruses by modulating ion homeostasis, cell signaling, cell cycle, and cell death. In this study, using pharmacological tools, we have identified that HIV utilizes distinct cellular potassium channels at various steps in its life cycle. Members of inwardly rectifying potassium (Kir) channel family, G protein-coupled (GIRK), and ATP-sensitive (KATP) are involved in HIV entry. Blocking these channels using specific inhibitors reduces HIV entry. Another member, Kir 1.1 plays a role post entry as inhibiting this channel inhibits virus production and release. These inhibitors are not toxic to the cells at the concentration used in the study. We have further identified the possible mechanism through which these potassium channels regulate HIV entry by using a slow-response potential-sensitive probe DIBAC4(3) and have observed that blocking these potassium channels inhibits membrane depolarization which then inhibits HIV entry and virus release as well. These results demonstrate for the first time, the important role of Kir channel members in HIV-1 infection and suggest that these K+ channels could serve as a safe therapeutic target for treatment of HIV/AIDS.

Downregulation of cytochrome c oxidase subunit 7A1 expression is important in enhancing cell proliferation in adenocarcinoma cells.

Mitochondrial Dysfunction has been implicated in multiple human diseases, including cancer. Among all cancer, lung cancer is the most common type of cancer worldwide with low survival rates. Mammals possess multiple subunits of the mitochondrial enzyme Cytochrome C oxidase (COX). The COX subunits are expressed in a tissue specific manner and have been implicated in cancer cell metabolism although their molecular and regulatory mechanisms are not clearly understood. In this study, we aimed at identifying novel gene signatures in lung cancer. We performed extensive analysis of seven different Gene Expression Omnibus (GEO) datasets pertaining to different stages of lung adenocarcinoma and identified that multiple subunits of COX genes are differentially expressed in these patients. Amongst all COX genes, the expression of COX7A1 gene was observed to be highly down regulated in these patients. In order to validate the GEO datasets, we looked at the expression of multiple COX genes using quantitative real time PCR (qPCR) using human lung adenocarcinoma cell line A549. Our results confirmed that COX 7A1 gene expression was indeed highly reduced in these cells. Overexpression of COX7A1 in human lung cancer cells led to inhibition of cell proliferation and increase in cell death via apoptosis. These results indicated that low level of COX7A1 gene expression is essential to regulate cell viability and inhibit cell death in lung adenocarcinoma. Our study has identified COX7A1 as a novel gene that might play a crucial role in the etiology of lung adenocarcinoma and can serve as a biomarker for lung cancer disease progression.