Five New Genome Types of Adenovirus Type 37 Caused Epidemic Keratoconjunctivitis in Sapporo, Japan, for More Than 10 Years

Abstract

Human adenovirus type 37 (HAdV-37) is a major cause of epidemic keratoconjunctivitis and has recently been the largest causative agent of keratoconjunctivitis in Japan. To investigate the genetic characteristics of HAdV-37 strains isolated in Sapporo, we analyzed the genome types and genetic relationships of 51 strains isolated there from 1990 through 2001. By using DNA restriction analysis, eight genome types (HAdV-37/D1, HAdV-37/D3, and HAdV-37/D6 to HAdV-37/D11) were identified, including five new ones. The restriction fragments of these genome types shared more than 95% identity with those of the prototype strain. By DNA sequence analysis, five and three single nucleotide substitutions, respectively, were found in partial sequences of the hexon and fiber genes. The combinations of mutations resulted in four hexon and fiber types (hx1 to hx4 and f1 to f4) and six hexon/fiber pairs (hx1/f1, hx2/f1, hx1/f2, hx1/f3, hx3/f4, and hx4/f4). The six pairs correlated well with certain genome types. In all three epidemics of keratoconjunctivitis to strike Sapporo in the past 12 years, specific genome types and fiber types were usually isolated: in the first epidemic, HAdV-37/D1 (f1) and HAdV-37/D3 (f1); in the second, HAdV-37/D6 (f2) and HAdV-37/D8 (f3); and in the third, HAdV-37/ D10 (f4) and HAdV-37/D11 (f4). We conclude that mutations in the adenovirus genome occurred chronologically and that certain mutations were correlated with the epidemics of adenoviral keratoconjunctivitis.

Novel Human Adenovirus Causing Nosocomial Epidemic Keratoconjunctivitis

“…These viruses originally were isolated from patients with EKC in 1951EKC in , 1955EKC in , and 1976. To date, several variants of these viruses have been reported (2,6,37), but none of the new serotypes causes EKC. The serotype of any strain isolated from a patient is defined on the basis of its immunological distinctiveness, such as that determined by quantitative neutralization with type-specific antisera.…”

“…This method has successfully classified the 51 prototype strains of HAdVs into the six designated species, as approved by the International Committee on Taxonomy of Viruses. Over the last 30 years, we have applied this molecular diagnosis to the identification of hundreds of isolates and swabs without virus isolation from patients from different parts of the world with EKC and lower respiratory tract infections (5,6,21,25,33).…”

Epidemic Keratoconjunctivitis Due to the Novel Hexon-Chimeric-Intermediate 22,37/H8 Human Adenovirus

“…We have recently determined the partial hexon sequences of all 51 prototype strains and developed a rapid and reliable method for diagnosis based on phylogenetic analysis (22,28). This method successfully classified the 51 prototype strains of HAdVs into the six designated species, as approved by the International Committee on Taxonomy of Viruses; we have applied molecular diagnosis to identify hundreds of isolates or swabs obtained over the last 30 years from patients with EKC and lower respiratory tract infections from different parts of the world (5,6,18,22,28). Through such study, we found another novel HAdV from nosocomially infected patients with EKC (17).…”

“…In Japan, we had four large outbreaks of EKC infections during the period from 1990 to 2001 and identified HAdV-37 as the causative agent by our methods (6). We also analyzed the genome types of HAdV-37 isolates and found five new genome types of HAdV-37.…”

Nucleotide sequence variation in the hexon gene of human adenovirus type 8 and 37 strains from epidemic keratoconjunctivitis patients in Japan

“…Recently, the nucleotide sequences in the hexon and fiber gene of all HAdV serotypes were determined and are now often used as targets for the detection of HAdV DNA and serotyping (Pring-Akerblom et al, 1999;Heim et al, 2003;Fujimoto et al, 2004;Sarantis et al, 2004;Shimada et al, 2004;Casas et al, 2005;Miura-Ochiai et al, 2007). Further, nucleotide substitutions in the hexon and fiber genes of strains from EKC patients have been observed, and the appearance of these substitutions appears to coincide with EKC epidemics (Ariga et al, 2005). Moreover, hexon chimeric intermediate HAdV strains have been isolated from EKC patients in Japan since 2003 .…”