Fatal Human Neurologic Infection Caused by Pigeon Avian Paramyxovirus-1, Australia

Abstract

Avian paramyxovirus type 1 (APMV-1) is a virus of birds that results in a range of outcomes, from asymptomatic infections to outbreaks of systemic respiratory and neurologic disease, depending on the virus strain and the avian species affected. Humans are rarely affected; those who are predominantly experience mild conjunctivitis. We report a fatal case of neurologic disease in a 2-year-old immunocompromised child in Australia. Metagenomic sequencing and histopathology identified the causative agent as the pigeon variant of APMV-1. This diagnosis should be considered in neurologic conditions of undefined etiologies. Agnostic metagenomic sequencing methods are useful in such settings to direct diagnostic and therapeutic efforts.

Keywords: Australia; Newcastle disease virus; avian paramyxovirus-1; brain; histopathology; metagenomics; pigeon paramyxovirus type 1; viruses; zoonoses.

Figure 1

Histology of brain tissue and imaging from a fatal neurologic infection in an immunocompromised child in Australia that was caused by APMV-1. A) Brain biopsy showing extensive cortical necrosis with a dense infiltrate of macrophages. Hematoxylin and eosin stain; original magnification ×20. B) Immunohistochemistry of brain biopsy showing cytoplasmic APMV-1 nucleoprotein, probably in neurons, with axon-like processes (arrowheads). Original magnification ×20 (inset ×40). C) Immunohistochemistry of APMV-1 nucleoprotein, demonstrating the absence of immunolabeling in normal brain tissue. APMV, avian paramyxovirus.

Figure 2

Magnetic resonance imaging of the brain of an immunocompromised child with avian paramyxovirus type 1 infection, Australia. Image, captured 16 days after hospital admission, shows predominantly left frontal and insular T2 signal hyperintensity evolving into laminar necrosis (white arrow) and hyperintensity of deep gray-matter structures (red arrows).

Figure 3

Genomic markers of virulence in avian paramyxovirus type 1 strain in an immunocompromised child in Australia. An analysis of both P and F genes indicated the strain would likely be classified as virulent based on P-gene editing; possible alternate reading frames were detected in mapped sequence reads (left side of panel). The F gene protein sequence carries a polybasic cleavage site at amino acid positions 112–116 (region on right of panel). CDS, coding sequences; F, fusion protein; G, glycoprotein; HN, hemagglutinin-neuraminidase protein; L, large protein; M, matrix protein; NP, nucleoprotein; P, polymerase-associated phosphoprotein.

Figure 4

Phylogenetic classification of avian paramyxovirus type 1 strain from an immunocompromised child in Australia (bold) using the large polymerase protein sequence. Node support values show Shimodaira-Hasegawa—like approximate likelihood ratio test statistics with branch lengths proportional to the scale. GenBank accession numbers are provided for reference sequences. Scale bar indicates number of substitutions per site.

Figure 5

Phylogeny of avian paramyxovirus type 1 strain from an immunocompromised child in Australia (bold). Tree was prepared from MAFFT-aligned fusion gene sequences of genotype VI sublineage 2.1.1.2.2 strains (classified as pigeon avian paramyxovirus 1) using PhyML with the Hasegawa-Kishino-Yano + gamma DNA substitution model and rooted with a genotype VI sublineage 2.1.1.2.1 outgroup (HM063425/Pigeon/CHN/P4). Red dot indicates virus from this case; GenBank accession numbers are provided for reference sequences. Gray box indicates the branch containing the virus we identified, expanded to show detail. Colored circles at tips indicate country of sampling. The virus from our study appears to be related to viruses circulating in Australia since at least 2011. Node support values show Shimodaira-Hasegawa—like approximate likelihood ratio test statistics; branch lengths are proportional to the scale of the number of substitutions per site. Scale bars indicate number of substitutions per site. All strains used in this analysis are listed in the Appendix.