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

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.

Keywords: Fuchs’ uveitis syndrome; Genomic characterization of rubella virus; Rubella virus.

Fig. 1

This photo depicts the heterochromia of iris, the lighter eye is the affected eye.

Fig. 2

This photo shows the pigmented chorioretinal scars centrally from old inflammation. The white areas are previous cryotherapy scars placed at the time of the original retinal detachment. In the further periphery indentation from the scleral buckle is noted.

Fig. 3

The genetic relationships of the 739 nt sequences were inferred using the Neighbor-Joining method. The percentage of replicate trees (70% or greater) in which the associated taxa clustered together in the bootstrap test (1000 replicates) are shown next to the branches. The genetic distances were computed using the Maximum Composite Likelihood method and are in units of the number of base substitutions per site. All taxa are labeled with WHO names. The Scranton sequence is marked with a circle.