Next Article in Journal
A Multiplex RT-PCR Assay to Detect and Discriminate Porcine Reproductive and Respiratory Syndrome Viruses in Clinical Specimens
Next Article in Special Issue
Hepatitis C Virus-Induced Autophagy and Host Innate Immune Response
Previous Article in Journal
Characterization of Two Historic Smallpox Specimens from a Czech Museum
Previous Article in Special Issue
The Interaction between Nidovirales and Autophagy Components
Article Menu
Issue 8 (August) cover image

Export Article

Open AccessArticle
Viruses 2017, 9(8), 201; doi:10.3390/v9080201

Importance of Autophagy in Mediating Human Immunodeficiency Virus (HIV) and Morphine-Induced Metabolic Dysfunction and Inflammation in Human Astrocytes

1
Department of Immunology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA
2
Department of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA
3
National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, VA 20110, USA
*
Author to whom correspondence should be addressed.
Received: 9 June 2017 / Revised: 24 July 2017 / Accepted: 24 July 2017 / Published: 28 July 2017
(This article belongs to the Special Issue Viruses and Autophagy)
View Full-Text   |   Download PDF [2355 KB, uploaded 1 August 2017]   |  

Abstract

Under physiological conditions, the function of astrocytes in providing brain metabolic support is compromised under pathophysiological conditions caused by human immunodeficiency virus (HIV) and opioids. Herein, we examined the role of autophagy, a lysosomal degradation pathway important for cellular homeostasis and survival, as a potential regulatory mechanism during pathophysiological conditions in primary human astrocytes. Blocking autophagy with small interfering RNA (siRNA) targeting BECN1, but not the Autophagy-related 5 (ATG5) gene, caused a significant decrease in HIV and morphine-induced intracellular calcium release. On the contrary, inducing autophagy pharmacologically with rapamycin further enhanced calcium release and significantly reverted HIV and morphine-decreased glutamate uptake. Furthermore, siBeclin1 caused an increase in HIV-induced nitric oxide (NO) release, while viral-induced NO in astrocytes exposed to rapamycin was decreased. HIV replication was significantly attenuated in astrocytes transfected with siRNA while significantly induced in astrocytes exposed to rapamycin. Silencing with siBeclin1, but not siATG5, caused a significant decrease in HIV and morphine-induced interleukin (IL)-8 and tumor necrosis factor alpha (TNF-α) release, while secretion of IL-8 was significantly induced with rapamycin. Mechanistically, the effects of siBeclin1 in decreasing HIV-induced calcium release, viral replication, and viral-induced cytokine secretion were associated with a decrease in activation of the nuclear factor kappa B (NF-κB) pathway. View Full-Text
Keywords: autophagy; human immunodeficiency virus; neurotransmitters; inflammation; morphine; astrocytes autophagy; human immunodeficiency virus; neurotransmitters; inflammation; morphine; astrocytes
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Rodriguez, M.; Lapierre, J.; Ojha, C.R.; Estrada-Bueno, H.; Dever, S.M.; Gewirtz, D.A.; Kashanchi, F.; El-Hage, N. Importance of Autophagy in Mediating Human Immunodeficiency Virus (HIV) and Morphine-Induced Metabolic Dysfunction and Inflammation in Human Astrocytes. Viruses 2017, 9, 201.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Viruses EISSN 1999-4915 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top