Molecular analysis of adenovirus isolates from vaccinated and unvaccinated young adults

Abstract

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.

FIG. 1.

Proportional distribution of adenovirus serotypes from febrile respiratory surveillance in military recruit camps from 1996 to 2002.

FIG. 2.

Ad4 and Ad7 hexon maximum-parsimony protein tree with canine Ad1 root. Isolates sequenced in the present study are labeled according to the following format: last two digits of accession number of identical sequence.location of isolation.year of isolation.vaccination status. FB, Fort Benning; FJ, Fort Jackson; FLW, Fort Leonard Wood; LACK, Lackland; GL, Great Lakes; MCRD, Marine Corps Recruit Depot; V, vaccinated; UV, unvaccinated. Full accession numbers appear once in parentheses. Accession numbers in boldface correspond to those in Fig. 3. Multiple accession numbers among identical protein sequences are due to DNA sequences with silent mutations. Bootstrap values greater than 50 (of 100 total bootstraps) are shown. Rescaled consistency index = 0.97.

FIG. 3.

Amino acid polymorphisms within aligned Ad7 (a) and Ad4 (b) sequence sets. Conserved positions are omitted, and residues identical to first sequences are represented by a period. Numbers refer to the amino acid position according to alignment with the Gomen prototype (AF065065) (a) and the Ad4 vaccine strain (AF065063) (b). Isolates correspond to those in boldface in Fig. 2.