Human Pegivirus in Patients with Encephalitis of Unclear Etiology, Poland

Abstract

Human pegivirus (HPgV), previously called hepatitis G virus or GB virus C, is a lymphotropic virus with undefined pathology. Because many viruses from the family Flaviviridae, to which HPgV belongs, are neurotropic, we studied whether HPgV could infect the central nervous system. We tested serum and cerebrospinal fluid samples from 96 patients with a diagnosis of encephalitis for a variety of pathogens by molecular methods and serology; we also tested for autoantibodies against neuronal antigens. We found HPgV in serum and cerebrospinal fluid from 3 patients who had encephalitis of unclear origin; that is, all the markers that had been tested were negative. Single-strand confirmation polymorphism and next-generation sequencing analysis revealed differences between the serum and cerebrospinal fluid-derived viral sequences, which is compatible with the presence of a separate HPgV compartment in the central nervous system. It is unclear whether HPgV was directly responsible for encephalitis in these patients.

Keywords: GB virus C; Poland; compartmentalization; encephalitis; hepatitis; human pegivirus; pegivirus; viruses.

Figure 1

Single-strand conformation polymorphism analysis of 5′ UTR and E2 region human pegivirus amplicons from 3 patients with encephalitis of unclear origin, Poland, 2012–2015. CSF, cerebrospinal fluid; S, serum; UTR, untranslated region.

Figure 2

Phylogenetic analysis of A) 5′ UTR and B) E2 region sequences of human pegivirus from 3 patients with encephalitis of unclear origin, Poland, 2012–2015. Phylogenic trees were generated using ClustalX version 2.0 (http://www.clustal.org/clustal2/). Viral variant frequencies follow haplotype number. Red indicates patient 1; blue, patient 2; green, patient 3. Scale bars indicate number of nucleotide substitutions per site. C, cerebrospinal fluid; S, serum; UTR, untranslated region.

Figure 3

Comparison of E2 region human pegivirus sequences amplified from serum and cerebrospinal fluid from 3 patients with encephalitis of unclear origin, Poland, 2012–2015. Numbers in parentheses represent the number of reads representing a given sequence. Shading indicates sequences unique to cerebrospinal fluid. Nucleotide numbering follows the reference strain published by Linnen et al (2) (GenBank accession no. NC_001710.1). C, cerebrospinal fluid; S, serum.

Figure 4

Comparison of amino acid composition of E2 region human pegivirus sequence variants amplified from serum and cerebrospinal fluid from 3 patients with encephalitis of unclear origin, Poland, 2012–2015. Numbers in parentheses represent the number of reads representing a given sequence. Shading indicates sequences unique to cerebrospinal fluid. C, cerebrospinal fluid; S, serum.