Lethal Respiratory Disease Associated with Human Rhinovirus C in Wild Chimpanzees, Uganda, 2013

Abstract

We describe a lethal respiratory outbreak among wild chimpanzees in Uganda in 2013 for which molecular and epidemiologic analyses implicate human rhinovirus C as the cause. Postmortem samples from an infant chimpanzee yielded near-complete genome sequences throughout the respiratory tract; other pathogens were absent. Epidemiologic modeling estimated the basic reproductive number (R₀) for the epidemic as 1.83, consistent with the common cold in humans. Genotyping of 41 chimpanzees and examination of 24 published chimpanzee genomes from subspecies across Africa showed universal homozygosity for the cadherin-related family member 3 CDHR3-Y₅₂₉ allele, which increases risk for rhinovirus C infection and asthma in human children. These results indicate that chimpanzees exhibit a species-wide genetic susceptibility to rhinovirus C and that this virus, heretofore considered a uniquely human pathogen, can cross primate species barriers and threatens wild apes. We advocate engineering interventions and prevention strategies for rhinovirus infections for both humans and wild apes.

Keywords: CDHR3; CDHR3-C529; CDHR3-Y529; Picornaviridae; Uganda; anthroponoses; asthma; cadherin; chimpanzee; common cold; enterovirus; epidemic; epidemiology; human rhinovirus; outbreak; respiratory disease; respiratory infections; rhinovirus; rhinovirus C; virology; viruses; zoonoses.

Figure 1

Epidemic curve of respiratory illness in the Kanyawara chimpanzee community, Uganda, 2013. Observational data on clinical severity (mild or severe) of respiratory signs (coughing and sneezing) were obtained and compiled into weekly measurements. The proportions of animals showing signs of respiratory illness are displayed by severity. Dashed line indicates 2013 mean rate of respiratory signs, and dotted line indicates 2 SD above that mean. Asterisks above bars indicate the timing of individual animal deaths.

Figure 2

Recombination between viral genotypes rhinovirus C45 and C11 leading to RV-C45-cpz1-2013, the strain identified in the Kanyawara chimpanzee community, Uganda, 2013. Analyses were performed in RDP4 (17) on aligned rhinovirus C genome sequences of 36 known genotypes. Each alignment entry encoded the full or nearly full polyprotein gene sequence, but some sequences were missing fragments (<400 bp) of their respective 5′-UTRs (Δ seq, yellow box at left). The 3′ poly(A) tail was not included. A recombination event between the 2 viruses shown (GenBank nos. JN837686 and EU840952) is the most likely event among all full alignment comparisons (window size 20 bps) according to 6 of the 9 RDP4 algorithms. The average p values were RDP 2.8 × 10⁻⁸¹, GENECONV 3.0 × 10⁻⁷⁰, MaxChi 1.4 × 10⁻¹⁸, Chimaera 2.1 × 10⁻²¹, SiScan 3.6 × 10^–34, and 3Seq 1.5 × 10⁻²⁷. BootScan, PhylPro, and LARD made no call for these particular parents. Purple box in the 5′-UTR denotes the 99% breakpoint confidence level (combined). Dashed box indicates the position of the most likely swapped fragment. The (Monte Carlo corrected) probability for this event is 2.8 × 10⁻⁸¹. The virus map is scaled to the alignment. Conf, confidence level; RV-C, rhinovirus C; Δ seq, missing sequence; UTR, untranslated region.

Figure 3

Phylogenetic tree of rhinovirus C variants. The tree was constructed from a codon-based alignment (6,234 positions) of the new chimpanzee-derived sequence identified in the Kanyawara chimpanzee community, Uganda, 2013 (indicated by the asterisk and chimpanzee silhouette), and all human-derived RV-C complete polyprotein gene sequences available in GenBank as of December 18, 2016, with rhinoviruses A and B from the RefSeq database included as outgroups. We created alignments using the MAFFT algorithm (18) implemented in the computer program Translator X (19), with the Gblocks algorithm (20) applied to remove poorly aligned regions. We constructed trees using the maximum-likelihood method implemented in PhyML (22), with best-fit models of molecular evolution estimated from the data by using jModelTest (21). Circles on nodes indicate statistical confidence on the basis of 1,000 bootstrap replicates of the data (closed circles 100%; open circles >75%). Scale bar indicates nucleotide substitutions per site. GenBank accession numbers and other details of the RV-C sequences included in the analysis are in Technical Appendix Table).