A novel adenovirus species associated with an acute respiratory outbreak in a baboon colony and evidence of coincident human infection

Abstract

Adenoviruses (AdVs) are DNA viruses that infect many vertebrate hosts, including humans and nonhuman primates. Here we identify a novel AdV species, provisionally named "simian adenovirus C (SAdV-C)," associated with a 1997 outbreak of acute respiratory illness in captive baboons (4 of 9) at a primate research facility in Texas. None of the six AdVs recovered from baboons (BaAdVs) during the outbreak, including the two baboons who died from pneumonia, were typeable. Since clinical samples from the two fatal cases were not available, whole-genome sequencing of nasal isolates from one sick baboon and three asymptomatic baboons during the outbreak was performed. Three AdVs were members of species SAdV-C (BaAdV-2 and BaAdV-4 were genetically identical, and BaAdV-3), while one (BaAdV-1) was a member of the recently described SAdV-B species. BaAdV-3 was the only AdV among the 4 isolated from a sick baboon, and thus was deemed to be the cause of the outbreak. Significant divergence (<58% amino acid identity) was found in one of the fiber proteins of BaAdV-3 relative to BaAdV-2 and -4, suggesting that BaAdV-3 may be a rare SAdV-C recombinant. Neutralizing antibodies to the other 3 AdVs, but not BaAdV-3, were detected in healthy baboons from 1996 to 2003 and staff personnel from 1997. These results implicate a novel adenovirus species (SAdV-C) in an acute respiratory outbreak in a baboon colony and underscore the potential for cross-species transmission of AdVs between humans and nonhuman primates. IMPORTANCE Adenoviruses (AdVs) are DNA viruses that infect many animals, including humans and monkeys. In 1997, an outbreak of acute respiratory illness from AdVs occurred in a baboon colony in Texas. Here we use whole-genome sequencing and antibody testing to investigate new AdVs in baboons (BaAdVs) during the outbreak, one of which, BaAdV-3, came from a sick animal. By sequence analysis, BaAdV-3 may be a recombinant strain that arose from a related BaAdV found in baboons nearby in the colony (who were not sick) and yet another unknown AdV. We also found antibodies to these new BaAdVs in baboons and staff personnel at the facility. Taken together, our findings of a new AdV species as the cause of an acute respiratory outbreak in a baboon colony underscore the ongoing threat from emerging viruses that may carry the potential for cross-species transmission between monkeys and humans.

FIG 1

Epidemiological features of the 1997 baboon adenovirus outbreak. Map of the baboon nursery during the 1997 outbreak with cages situated in two separate rooms, showing the locations of baboons who died from pneumonia (skeleton), baboons who became clinically ill with respiratory symptoms but survived (red), and asymptomatic baboons (brown). The novel AdVs genetically characterized in this study (BaAdV-1 to BaADV-4) were isolated from nasal swabs from both sick (B5) and asymptomatic (B4, B8, and B9) baboons.

FIG 2

Genomic coverage of 4 novel baboon adenoviruses (BaAdVs) by deep sequencing. Part of the viral genome was recovered directly from deep sequencing reads using a de novo assembly approach (black bars). After completion of the genome and confirmation by Sanger sequencing, deep sequencing reads are mapped to the corresponding AdV genome. The coverage (y axis) achieved at each position along the genome (x axis) is plotted on a logarithmic scale. Abbreviation: nt, nucleotide.

FIG 3

Genome organization of BaAdV-1 and BaAdV-2/-4 and pairwise alignment with related adenoviruses. (A and B) Maps of the genome organization corresponding to two baboon AdVs, BaAdV-1 (A), a species SAdV-B AdV, and BaAdV-2/-4 (B), a novel species SAdV-C AdV, are shown. Boxes above the central black line represent genes on the forward strand, while boxes below the black line represent genes on the reverse strand. Early region genes are shaded in gray. The scanning nucleotide pairwise identities of BaAdV-1 (A) and BaAdV-2/-4 (B) relative to selected related human (yellow), simian (brown), or novel baboon (pink) AdVs are shown ranked in order of decreasing overall percent identity. The x axis refers to the nucleotide position along the genome. Abbreviations: ITR, inverted terminal repeat; pTP, precursor terminal protein; ORF, open reading frame; DNApol, DNA polymerase; DBP, DNA binding protein; CR1, complement receptor 1; RID-α, receptor internalization and degradation.

FIG 4

Amino acid phylogenetic analysis of BaAdV-1, BaAdV-2/-4, and BaAdV-3 relative to other adenoviruses. (A) Hexon; (B) penton base; (C) DNA polymerase; (D) fiber. Representative primate AdVs in species A to G, SAdV-A, and SAdV-B, and nonprimate AdVs, were included in the phylogenetic analysis. Bayesian support levels are displayed at each branching point. The 4 novel BaAdVs identified in this study and the proposed “species SAdV-C” designation are highlighted in red. Scale bars indicate the number of amino acid substitutions per site. Abbreviations and GenBank accession numbers are given in the text.

FIG 5

Amino acid pairwise identities of BaAdV-1 and BaAdV-2/-4 relative to other adenoviruses. Comparisons are made against representative human, simian, and murine AdVs. The amino acid pairwise identity table is displayed as a heat map; colors ranging from blue to white to red correspond to pairwise identities of 10 to 100% (color bar). The black cells denote AdVs that lack short fibers.

FIG 6

Evidence for recombination in species SAdV-C adenovirus BaAdV-3. Similarity (top) and bootscanning (bottom) plots of AdVs in species SAdV-A, SAdV-B, SAdV-C, -F, and -G relative to BaAdV-3 are shown. Bootscanning analysis reveals likely recombination breakpoints in the region corresponding to the divergent short fiber 1 gene (asterisk). The x axis refers to the nucleotide position. The genome organization map is annotated in the same fashion as in Fig. 2. Abbreviation: nt, nucleotide.