Abstract
A divergent rhabdovirus was discovered in the bloodstream of a 15-year-old girl with Nodding syndrome from Mundri West County in South Sudan. Nodding syndrome is a progressive degenerative neuropathy of unknown cause affecting thousands of individuals in Sub-Saharan Africa. The index case was previously healthy until she developed head-nodding seizures four months prior to presentation. Virus discovery by VIDISCA-NGS on the patient’s plasma detected multiple sequence reads belonging to a divergent rhabdovirus. The viral load was 3.85 × 103 copies/mL in the patient’s plasma and undetectable in her cerebrospinal fluid. Further genome walking allowed for the characterization of full coding sequences of all the viral proteins (N, P, M, U1, U2, G, U3, and L). We tentatively named the virus “Mundri virus” (MUNV) and classified it as a novel virus species based on the high divergence from other known viruses (all proteins had less than 43% amino acid identity). Phylogenetic analysis revealed that MUNV forms a monophyletic clade with several human-infecting tibroviruses prevalent in Central Africa. A bioinformatic machine-learning algorithm predicted MUNV to be an arbovirus (bagged prediction strength (BPS) of 0.9) transmitted by midges (BPS 0.4) with an artiodactyl host reservoir (BPS 0.9). An association between MUNV infection and Nodding syndrome was evaluated in a case–control study of 72 patients with Nodding syndrome (including the index case) matched to 65 healthy households and 48 community controls. No subject, besides the index case, was positive for MUNV RNA in their plasma. A serological assay detecting MUNV anti-nucleocapsid found, respectively, in 28%, 22%, and 16% of cases, household controls and community controls to be seropositive with no significant differences between cases and either control group. This suggests that MUNV commonly infects children in South Sudan yet may not be causally associated with Nodding syndrome.
Highlights
In August 2018, a 15-year-old girl was evaluated at the Nodding syndrome (NS) study clinic at Lui Hospital, Mundri East County, South Sudan, for clinical and laboratory evaluation for study purposes
The patient had an axillary temperature of 36.2 ◦ C, a heart rate of 100 bpm, a respiratory rate of 28 bpm, a blood pressure of 90 over 60 mmHg, and a body mass index (BMI) of 18.4
Because virus consistently shares a closest common ancestor with Ekpoma virus 2 (EKV2) and bethe N and the G protein sequences share at most 57% amino acid identity with its closest longs to a monophyletic clade of tibroviruses (family: Rhabdoviridae, genus: Tibrovirus, Figrelatives (Table 2), we propose this virus to be a novel virus species, in line with ICTV
Summary
One hypothesis that has been proposed is that NS may be caused by a novel neurotropic virus [2]. Previous attempts to identify a potential viral cause have focused on a limited number of known viruses and were unsuccessful; these studies did not consider novel viruses [3]. To explore a potential novel viral cause of NS, we performed virus-discovery assays using VIDISCA-NGS on the plasma and cerebrospinal fluid of children with new-onset. VIDISCA-NGS allows unbiased detection of known and unknown RNA and DNA viruses in a plethora of clinical specimen, and it was previously used to discover viruses such as human coronavirus NL63 [4] and Ntwetwe orthobunyavirus [5]. We report the discovery of a novel rhabdovirus from the plasma of a child with new-onset NS from.
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