June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Torque Teno Virus Associated with Endophthalmitis
Author Affiliations & Notes
  • Aaron Lee
    Department of Ophthalmology, Washington University in St Louis, St Louis, MO
  • Lakshmi Akileswaran
    Department of Ophthalmology, University of Washington School of Medicine, Seattle, WA
  • Michael Tibbetts
    Mid Atlantic Retina, Wills Eye Institute, Philadelphia, PA
  • Sunir Garg
    Mid Atlantic Retina, Wills Eye Institute, Philadelphia, PA
  • Russell Van Gelder
    Department of Ophthalmology, University of Washington School of Medicine, Seattle, WA
  • Footnotes
    Commercial Relationships Aaron Lee, Cogent 14 Productions LLC (threeplus.org) (P); Lakshmi Akileswaran, None; Michael Tibbetts, None; Sunir Garg, Lux (F), EyeGate (F), Regeneron (F), Genentech (F), Allergan (C); Russell Van Gelder, Novartis (F)
  • Footnotes
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Investigative Ophthalmology & Visual Science June 2013, Vol.54, 1106. doi:https://doi.org/
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      Aaron Lee, Lakshmi Akileswaran, Michael Tibbetts, Sunir Garg, Russell Van Gelder; Torque Teno Virus Associated with Endophthalmitis. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1106. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: To investigate the presence of viral pathogens in culture-positive and -negative infectious endophthalmitis using deep DNA sequencing techniques.

Methods: In a prospective fashion, 7 fluid samples from uninflamed eyes and 21 consecutive samples from infectious endophthalmitis diagnosed by a retinal specialist were collected by vitreous or aqueous tap. Using Biome Representational in Silico Karyotyping (BRiSK), a type IIB DNA restriction enzyme (BsaX1) was used to create a representational set of 27-mer DNA tags for each sample and sequenced using a massively parallel sequencing platform. Tags that uniquely matched viral DNA were included for further analysis. Quantitative PCR was performed to verify the presence of pathogens.

Results: Fifteen of the 21 endophthalmitis samples (71.4%) were positive for the Torque Teno Virus (TTV) including 7 out of 7 (100%) of culture-negative samples. In contrast, 0 out of 7 (0%) of the normal vitreous samples were positive for TTV (p = 0.001 by Fisher Exact). No other viruses were recovered in these samples, and the presence and absence of TTV were verified by PCR. A mean of 369.4 TTV tags were recovered per sample (range of 1 to 3,580 tags). Quantitative PCR showed relative multiplicity of infection compared to human genomic DNA of up to 258, suggesting a productive infection.

Conclusions: BRiSK is an effective method for identifying viral presence in culture-positive and culture-negative endophthalmitis. TTV is a small non-enveloped single stranded DNA virus with a genome size of approximately 3.8 kb found frequently in the serum of normal individuals (90%) with no clear pathogenic role. TTV has been shown to modulate the immune system by increasing proinflammatory cytokine production of interferon γ, IL-6, and IL-12 through Toll-like receptor 9. The finding of TTV in high viral load in infectious endophthalmitis samples leads to a number of possible hypotheses including: inflammation directly related to infection, TTV modulating the immune system to increase susceptibility to bacterial co-infection, a proinflammatory state causing culture negative endophthalmitis, or breakdown of the blood-retinal barrier allowing the virus to replicate in the vitreous.

Keywords: 513 endophthalmitis • 746 uveitis-clinical/animal model • 496 detection  
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