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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2015

Open Access 01-12-2015 | Research

Sterile alpha motif and histidine/aspartic acid domain-containing protein 1 (SAMHD1)-facilitated HIV restriction in astrocytes is regulated by miRNA-181a

Authors: Sudheesh Pilakka-Kanthikeel, Andrea Raymond, Venkata Subba Rao Atluri, Vidya Sagar, Shailendra K Saxena, Patricia Diaz, Semithe Chevelon, Michael Concepcion, Madhavan Nair

Published in: Journal of Neuroinflammation | Issue 1/2015

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Abstract

Background

Although highly active antiretroviral therapy (HAART) has significantly reduced the morbidity and mortality in HIV patients, virus continues to reside in the central nervous system (CNS) reservoir. Hence, a complete eradication of virus remains a challenge. HIV productively infects microglia/macrophages, but astrocytes are generally restricted to HIV infection. The relative importance of the possible replication blocks in astrocytes, however, is yet to be delineated. A recently identified restriction factor, sterile alpha motif and histidine/aspartic acid domain-containing protein 1 (SAMHD1), restricts HIV infection in resting CD4+T cells and in monocyte-derived dendritic cells. However, SAMHD1 expression and HIV-1 restriction activity regulation in the CNS cells are unknown. Though, certain miRNAs have been implicated in HIV restriction in resting CD4+T cells, their role in the CNS HIV restriction and their mode of action are not established. We hypothesized that varying SAMHD1 expression would lead to restricted HIV infection and host miRNAs would regulate SAMHD1 expression in astrocytes.

Results

We found increased SAMHD1 expression and decreased miRNA expression (miR-181a and miR-155) in the astrocytes compared to microglia. We report for the first time that miR-155 and miR-181a regulated the SAMHD1 expression. Overexpression of these cellular miRNAs increased viral replication in the astrocytes, through SAMHD1 modulation. Reactivation of HIV replication was accompanied by decrease in SAMHD1 expression.

Conclusions

Here, we provide a proof of concept that increased SAMHD1 in human astrocytes is in part responsible for the HIV restriction, silencing of which relieves this restriction. At this time, this concept is of theoretical nature. Further experiments are needed to confirm if HIV replication can be reactivated in the CNS reservoir.
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Metadata
Title
Sterile alpha motif and histidine/aspartic acid domain-containing protein 1 (SAMHD1)-facilitated HIV restriction in astrocytes is regulated by miRNA-181a
Authors
Sudheesh Pilakka-Kanthikeel
Andrea Raymond
Venkata Subba Rao Atluri
Vidya Sagar
Shailendra K Saxena
Patricia Diaz
Semithe Chevelon
Michael Concepcion
Madhavan Nair
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2015
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-015-0285-9

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