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Front. Immunol. | doi: 10.3389/fimmu.2019.00901

Upregulated Papio cynocephalus Endogenous Retrovirus (PcEV) expression in acutely SIV-infected macaques correlates with expression of the interferon-stimulated gene STAT1.

 Emmanuel A. Maze1,  Claire Ham2, Jack Kelly1,  Lindsay Ussher1, Neil Almond2, Greg J. Towers3,  Neil Berry2* and  Robert Belshaw1*
  • 1University of Plymouth, United Kingdom
  • 2National Institute for Biological Standards and Control (NIBSC), United Kingdom
  • 3University College London, United Kingdom

Retroviral replication leaves a DNA copy in the host cell chromosome, and over millions of years such infection of germline cells has led to our genome sequence containing ~100,000 endogenous retrovirus (ERV) loci. Over time these loci have accrued mutations such as premature stop codons that prevent continued replication. However, many loci remain transcriptionally and translationally active today and ERVs have been implicated in interacting with the immune system. Using archived plasma and tissue samples from past experiments where macaques were infected with simian immunodeficiency virus (SIV), we explored how the expression of one of the macaque ERVs responded to viral infection and whether this expression correlated with a measure of the innate immune response. Specifically, we measured the RNA levels of (a) an ERV (Papio cynocephalus Endogenous Retrovirus, PcEV), (b) a key gene in the interferon signalling pathway (STAT1) and (c) the exogenous pathogen (i.e. SIV). Bioinformatic analysis of the DNA sequences of the PcEV loci within the macaque reference genome sequences was consistent with potential protein expression but not ERV replication. However, quantitative RT-PCR analysis of DNase-treated RNA extracts from plasma derived from acute SIV-infection indicated PcEV RNA in 7 animals. PcEV expression was elevated by SIV infection in all tissues. Moreover, tissue PcEV and STAT1 RNA expression levels were correlated during acute SIV infection (Spearman correlation r=0.47; p-value=0.0091), especially in the spleen, but STAT1 levels were not correlated to either tissue or plasma SIV RNA levels. We speculate that intracellular PcEV RNA expression and induction of a key component of the interferon cascade are causally linked.

Keywords: endogenous retrovirus, STAT1, macaque, PcEV, SIV, innate immunity

Received: 28 Jan 2019; Accepted: 08 Apr 2019.

Edited by:

Gkikas Magiorkinis, National and Kapodistrian University of Athens, Greece

Reviewed by:

Mani Larijani, Memorial University of Newfoundland, Canada
Claudia Matteucci, University of Rome Tor Vergata, Italy  

Copyright: © 2019 Maze, Ham, Kelly, Ussher, Almond, Towers, Berry and Belshaw. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Neil Berry, National Institute for Biological Standards and Control (NIBSC), Potters Bar, England, United Kingdom, neil.berry@nibsc.org
Dr. Robert Belshaw, University of Plymouth, Plymouth, PL4 8AA, England, United Kingdom, robert.belshaw@plymouth.ac.uk