Genomic characterization of a persistent rubella virus from a case of Fuch’ uveitis syndrome in a 73 year old man

doi:10.1016/j.jcv.2015.06.084

Journal of Clinical Virology

Volume 69, August 2015, Pages 104-109

https://doi.org/10.1016/j.jcv.2015.06.084 Get rights and content

Highlights

•
This study supports the role of rubella virus as a cause of FUS.
•
It suggests that persistent RuV presence in the eye can be the cause of chronic vision problems.
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This rubella virus was a previously undetected genotype which is no longer circulating.
•
The eye had likely been persistently infected with rubella virus for at least 60 years.
•
The sequence of the virus is from the earliest rubella virus yet characterized.

Abstract

Background

Many cases of Fuchs’ uveitis have been associated with persistent rubella virus infection. A 73-year-old male patient with typical Fuchs’ Uveitis Syndrome (FUS) first experienced heterochromia of the left eye at the age fourteen, when rubella was endemic in the US.

Objectives

The purposes of this report are to describe the patient’s FUS clinical presentations and to characterize the virus detected in the vitreous fluid.

Study design

The patient underwent a therapeutic pars plana vitrectomy in May 2013. A real-time RT-PCR assay for rubella virus was performed on the vitreous fluid by Focus Diagnostics. Additional real-time RT-PCR assays for rubella virus detection and RT-PCR assays for generation of templates for sequencing were performed at the Centers for Disease Control and Prevention (CDC).

Results

The results from Focus Diagnostics were positive for rubella virus RNA. Real-time RT-PCR assays at CDC were also positive for rubella virus. A rubella virus sequence of 739 nucleotides was determined and phylogenetic analysis showed that the virus was the sole member of a new phylogenetic group when compared to reference virus sequences.

Conclusions

While FUS remains a clinical diagnosis, findings in this case support the association between rubella virus and the disease. Phylogenetic analysis provided evidence that this rubella virus was likely a previously undetected genotype which is no longer circulating. Since the patient had rubella prior to 1955, this sequence is from the earliest rubella virus yet characterized.

Section snippets

Background

Fuchs’ uveitis syndrome was originally described by Ernest Fuchs’ in 1906 [1]. It has variously been referred to as Fuchs’ heterochromic cyclitis, Fuchs’ heterochromic iridocyclitis, Fuchs’ heterochromic uveitis, and most recently Fuchs’ uveitis syndrome (FUS) [1], [2]. The typical characteristics of FUS include iris heterochromia, cyclitis, and cataract. Other characteristics of FUS include a mild anterior chamber reaction, the occurrence of small to medium-sized diffusely distributed stellate

Objectives

This report describes the molecular detection and genotypic characterization of rubella virus nucleic acid recovered from the vitreous fluid of a 73-year-old Pennsylvania man with a clinical diagnosis of FUS. The patient first experienced heterochromia of the left eye at age fourteen; thus, the rubella virus nucleic acid detected is likely due to rubella infection prior to 1953.

Rubella virus RNA detection

The vitreous fluid from the patient’s left eye collected at the time of vitrectomy was submitted to Focus Diagnostics (Cypress, CA) for the detection of DNA of T. gondii and RNA of rubella virus. The specimen was shipped on cold packs and RNA extraction was performed within 48 h of the specimen collection. At Focus Diagnostics, DNA/RNA was extracted from the sample using the MagNa Pure System (Roche Diagnostics, Indianapolis, IN). The T. gondii DNA was tested using a qualitative real-time PCR

Patient history and presentation

The patient was a 73-year-old male, born and raised in the United States, with chronic iritis in the left eye for which he had been on and off topical steroids for many years. He had a history of a repaired left eye retinal detachment performed elsewhere 8 years prior with scleral buckle. On admission, he revealed that he had good vision for a year after the repair of the retinal detachment, but then developed persistent debris and floaters. The examination showed a vision of 20/25 and 20/40 in

Discussion

Until recently, FUS remained a clinical diagnosis with an unknown etiology. The association between rubella infection and FUS was not recognized until 2004 [23].

On initial examination, the left eye showed an old scleral buckle with chorioretinal scarring and punched out choroidal lesions suggestive of toxoplasmosis. The patient also had notable vitreous debris and floaters suggestive of FUS. Therefore, the vitreous fluid was tested for the detection of T. gondii DNA and RuV RNA. An association

Conflict of interest

None.

Funding

None.

Ethical approval

Not required.

Randomized controlled trial

N/A.

Acknowledgements

We thank Dr. Pierre Rivailler and Dr. Roman Tatusov for helpful discussions and reading of the manuscript. The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention. Names of specific vendors, manufacturers, or products are included for public health and informational purposes; inclusion does not imply endorsement of the vendors, manufacturers, or products by the Centers for

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Nevertheless, when compared to the assay of the same technology (i.e. E1 assay), the new RT-qPCR assay showed clinical sensitivity of 99.4% when true rubella cases were tested. Since nearly 50% RuV clinical specimens have less than 100 copies per μL of viral RNA, the NSP#2 assay allows to confirm cases from various types of specimens, including granulomatous skin biopsies (Perelygina et al., 2019) and vitreous fluid (Abernathy et al., 2015). We further multiplexed the detection of both RuV and cellular reference gene without losing the sensitivity of RuV RNA detection.
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Nevertheless, laboratory confirmation of rubella virus infection in the newborn by either serologic or virus detection techniques is also critical, especially when only a single defect presents [48]. Other persistent rubella virus infections of clinical significance include Fuch’s Uveitis [49] and granuloma in primary immune deficient individuals [50•]. Humans appear to be the only species in which RuV circulates.
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View full text

Genomic characterization of a persistent rubella virus from a case of Fuch’ uveitis syndrome in a 73 year old man

Highlights

Abstract

Background

Objectives

Study design

Results

Conclusions

Section snippets

Background

Objectives

Rubella virus RNA detection

Patient history and presentation

Discussion

Conflict of interest

Funding

Ethical approval

Randomized controlled trial

Acknowledgements

Am. J. Ophthalmol.

Am. J. Ophthalmol.

Am. J. Ophthalmol.

Am. J. Ophthalmol.

J. Virol. Methods

J. Clin. Virol.

Am. J. Ophthalmol.

Professor Ernst Fuchs’ (1851–1930): a defining career in ophthalmology

Arch. Ophthalmol.

Fuchs’heterochromic cyclitis

Semin. Ophthalmol.

Confocal scan features of keratic precipitates in Fuchs’ heterochromic iridocyclitis

Cornea

Ocular manifestations of systemic disease: toxoplasmosis

Curr. Opin. Ophthalmol.

Pathogenesis of systemic lupus erythematosus

J. Clin. Pathol.

Immune Disease

Sarcoidosis

Semin. Ophthalmol.