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