MOLECULAR AND PHENOTYPIC CHARACTERIZATION OF EMERGING ADENOVIRUS 14 STRAIN ASSOCIATED WITH RECENT OUTBREAKS OF RESPIRATORY DISEASE IN THE UNITED STATES

Session ID:	S53
Author Name:	Adriana E. Kajon1, Xiaoyan Lu 2, Dean D. Erdman2, David Schnurr3, and David Metzgar4 1-Infectious Disease Program, Lovelace Respiratory Research Institute, Albuquerque, NM, USA,. 2-Division of Viral Diseases, Centers for Disease Control and Prevention, At
Country:	US
Conference Session:	Session I

Background: Among the species B2 adenovirus serotypes with a record of association with acute respiratory disease, Ad14 is by far the rarest. First discovered during an outbreak of acute respiratory disease among military recruits in 1955 in The Netherlands, and initially referred to as “agent De Wit”, Ad14 was subsequently isolated during similar outbreaks in Europe in the mid 1950s to early 1960s. The circulation of this serotype was not documented again until its detection in association with pediatric respiratory disease in Taiwan during 2001 and 2002. With no precedent of previous circulation in the United States, Ad14 has been continuously detected during outbreaks respiratory illness among military recruits throughout the United States since March 2006, and associated with civilian cases and outbreaks of severe pneumonia and deaths since as early as 2003, affecting both pediatric and adult patients in several states.

Methods and results: Following our hypothesis that the emerging Ad14 is a new DNA variant with increased fitness, restriction enzyme analysis of viral genomic DNA and select gene sequencing was carried out on a subset of Ad14 strains representing different years and geographic sites. All examined viruses were found to be identical and to belong to a new genome type named Ad14a, distinguishable from the prototype strain de Wit, Ad14p, by its unique BamHI and SmaI profiles. Consistent with the results of neutralization assays, sequencing of the hypervariable regions of the hexon gene HVR1-7 showed 99.4% sequence identity with Ad14p. All examined Ad14a isolates exhibited distinct mutations in the fiber gene and E1A coding region. One step growth curves and lateral spread studies in infected A549 cell monolayers showed a faster dissemination phenotype for the newly emerging Ad14a compared to the prototype strain de Wit.

Conclusions: The newly emerging Ad14 represents a novel genome type with intriguing mutations in the fiber knob and E1A coding region that may account for its apparent higher fitness and virulence.