2,3,7,8-Tetrachlorodibenzo-p-dioxin promotes BHV-1 infection in mammalian cells by interfering with iron homeostasis regulation
Authors: Carlo Irace
Alfredo Colonna
Giuseppe Iovane
Ugo Pagnini
Filomena Fiorito
Luisa De Martino
Antonio Di Pascale
Rita Santamaria
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: Iron metabolism; Iron Regulatory Proteins; TCDD; BHV-1; MDBK cells
Affiliations: Dipartimento di Medicina Veterinaria e Produzioni Animali, Università degli Studi di Napoli Federico II, Naples, Italy.

Abstract:  Mammalian cells require iron to satisfy metabolic needs or to accomplish specialized functions, and DNA viruses, like bovine herpesvirus 1 (BHV-1), require an iron-replete host to efficiently replicate, so that iron bioavailability is an important component of viral virulence. Cellular iron metabolism is coordinately controlled by the Iron Regulatory Proteins (IRP1 and IRP2), whose activity is affected by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a current and persistent environmental contaminant. Considering that TCDD enhances BHV-1 replication, herein we analyzed the effects of TCDD on iron metabolism during BHV-1 infection in MDBK cells, and presented evidences of a divergent modulation of IRP1 and IRP2 RNA-binding capacity. Moreover, an up-regulation of transferrin receptor 1 (TfR1) and a concomitant down-regulation of ferritin were observed. This scenario led to an expansion of the labile iron pool (LIP) and induces a significant enhance of viral titer, as confirmed by increased levels of BHV-1 infected cell protein 0 (bICP0), the major transcriptional regulatory protein of BHV-1. Taken together, our data suggest that TCDD increases the free intracellular iron availability thereby promoting the onset of BHV-1 infection and rendering bovine cells more vulnerable to the virus. 

Retracted: No

PubPeer comments:
 Fig 7A.  Representative images of tumor xenografts derived from HOS cells transfected with the miR-618 mimics or miR-NC . Rotated through 90 deg. ![file] This research group appears to be using the same ruler (distinguished by blemishes including a scrape to the left of 1 ) as four other teams at various institutions in various provinces. E.g. [Pang et al (2019)] , Fig 9A. ![] , 
 Figs 2C, 4C, 5C. ![file] Figs 2C, 4B, 6C from [Li et al (2019)] . ![file] Two panels (brown boxes) have so many points in common as to suggest that they somehow came from the same flow-cytometry data set. Here together (rescaled and with contrast adjustments for ease of comparison). ![file] , 
 Four flow-cytometry plots share most of their points in common, suggesting that they come from the same raw data file (differently gated and filtered). I have adjusted contrast and aspect ratios for ease of comparison. ![file] Here in context: Figs 2C, 4C, 5C again ![file] Figs 2C, 4B, 5F from [Li et al (2019)] . ![file] The right-hand panel is from Figs 2C, 4C, 5D of [Chen et al (2019)] . ![file] , 
 Two flow-cytometry plots share most of their points in common, suggesting that they come from the same raw data file (differently gated and filtered). I have adjusted contrast and aspect ratios for ease of comparison. ![file] Here in context: Fig 2C again; Fig 6c from [Wu et al (2020)] . ![file] ![file] ---------------------------------------------------------- Two flow-cytometry plots share most of their points in common, suggesting that they come from the same raw data file (differently gated and filtered). I have adjusted contrast and aspect ratios for ease of comparison. ![] Here in context. Right-hand panel is from Fig 4C. Left-hand panel is from Figs 2c, 4b, 6c, 7e of [Zhao et al (2020)] . ![] ![] , 
 Retracted [28 September 2021] . ------------------------------------ The Editor and Publisher of *OncoTargets and Therapy* wish to retract the published article. Concerns were raised over alleged image duplication in Figures 2C, 4C and 5C with similar images from unrelated articles, specifically: - Figure 2C, panel U2OS miR-NC appears to have been duplicated with a similar image in Figure 2C from Li et al, 2019 . - Figure 2C, panel U2OS miR-618 mimics appears to have been duplicated with a similar image from Figure 5c from Wu et al, 2020 . - Figure 4C, panel HOS si-MTDH appears to be have been duplicated with a similar image in Figure 4b from Zhao et al, 2020 . - Figure 5C, panel HOS miR-618 mimics+pCMV appears to have been duplicated with a similar image in Figure 2C from Li et al, 2019 and Figure 5D from Chen et al, 2019 . The authors did not respond to our queries and the Editor determined the findings of the study were no longer valid and advised for the article to be retracted. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u201cRetractedu201d. ,