Genome sequences of human adenovirus 14 isolates from mild respiratory cases and a fatal pneumonia, isolated during 2006-2007 epidemics in North America

Abstract

Background: Human adenovirus 14 (HAdV-14) is a recognized causative agent of epidemic febrile respiratory illness (FRI). Last reported in Eurasia in 1963, this virus has since been conspicuously absent in broad surveys, and was never isolated in North America despite inclusion of specific tests for this serotype in surveillance methods. In 2006 and 2007, this virus suddenly emerged in North America, causing high attack rate epidemics of FRI and, in some cases, severe pneumonias and occasional fatalities. Some outbreaks have been relatively mild, with low rates of progression beyond uncomplicated FRI, while other outbreaks have involved high rates of more serious outcomes.

Methodology and findings: In this paper we present the complete genomic sequence of this emerging pathogen, and compare genomic sequences of isolates from both mild and severe outbreaks. We also compare the genome sequences of the recent isolates with those of the prototype HAdV-14 that circulated in Eurasia 30 years ago and the closely related sequence of HAdV-11a, which has been circulating in southeast Asia.

Conclusions: The data suggest that the currently circulating strain of HAdV-14 is closely related to the historically recognized prototype throughout its genome, though it does display a couple of potentially functional mutations in the fiber knob and E1A genes. There are no polymorphisms that suggest an obvious explanation for the divergence in severity between outbreak events, suggesting that differences in outcome are more likely environmental or host determined rather than viral genetics.

Figure 1

Map of apparent open reading frames and their identities in the genome of the emerging North American HAdV-14p1.

Figure 2

Global pairwise comparison of multiple species B HAdV genomes.

Figure 3

E1A alignments. Alignment of selected E1A 28K amino acid sequences from HAdV-3, 7, 11, 14p, 14p1, and 21. Black arrow demarcates the S147 insertion, shared by HAdV-3, 7, and 21.

Figure 4

Fiber knob binding site alignment. Alignment of the amino acid sequences on the exposed regions of the fiber loops FG, HI, and IJ that are involved in binding to CD46. Black arrow demarcates the ΔK250-E251 deletion. All sequences were aligned using the ClustalX [40] alignment method. The following HAdV genomes (GenBank accession numbers) were used: HAdV-14p (AY803294), HAdV-11p (AY163756), HAdV-3 (NC_011203), HAdV-7 (AC_000018), and HAdV-21 (AY601633).