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Molecular Analysis of Adenovirus Isolates from Vaccinated and Unvaccinated Young Adults

Daniel A. Blasiole,¹ David Metzgar,¹ Luke T. Daum,² Margaret A. K. Ryan,¹ Jianguo Wu,¹ Christopher Wills,³ Charles T. Le,¹ Nikki E. Freed,¹ Christian J. Hansen,¹ Gregory C. Gray,^1, and Kevin L. Russell^1*

Department of Defense Center for Deployment Health Research, Naval Health Research Center, San Diego, California 92186-5122,¹ Brooks City-Base, San Antonio, Texas 78235,² Division of Biological Sciences, University of California, San Diego, La Jolla, California 92093³

Received 25 September 2003/ Returned for modification 10 October 2003/ Accepted 25 November 2003

Infections of adenovirus type 4 (Ad4) and Ad7 were discovered among previously vaccinated individuals through febrile respiratory illness surveillance at military recruit camps. Genetic analysis was performed on these isolates and a sample of adenovirus isolates from unvaccinated patients. Antigenic regions of the adenovirus hexon gene from 21 vaccinated and 31 unvaccinated patients were sequenced and compared to homologous regions of Ad4 and Ad7 vaccine strains and of other representative hexon sequences archived in GenBank. The phylogenetic distribution of sequences from vaccinated individuals closely resembled those from unvaccinated individuals. The most common Ad7 strain was the Ad7d2 hexon genotype, and the most common Ad4 strain was a genotype nearly identical to the recently discovered Z-G 95-873 Ad4 variant. Near exclusive isolation of Ad4 since 1999 indicates that the Ad4 variant is currently responsible for the vast majority of adenovirus morbidity in military recruit camps. Different ratios of nonsynonymous to synonymous nucleotide substitution rates in known antigenic regions compared to nonantigenic regions indicated positive selection for diversity in the antigenic regions and purifying selection in the nonantigenic regions.

Present address: College of Public Health, University of Iowa, Iowa City, IA 52242.

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