Genome Analysis of Adenovirus Type 7 and Adenovirus Type 11

Abstract

Purpose: To study the epidemiology of adenovirus type 7 (Ad 7) conjunctivitis and adenovirus type 11 (Ad 11) conjunctivitis in the Japanese population by determining the genome type and sub-genome type.

Methods: For Ad 7, we used 12 strains from patients with acute viral conjunctivitis and one strain from a patient with pneumonia. For Ad 11, we used 17 strains from patients with acute viral conjunctivitis and 3 strains from patients with cystitis. For Ad 7 genome typing, we used 11 DNA restriction endonucleases (REs) recognizing 6-or 7-base pair sequences, and for Ad 11 genome typing, we used 7 REs. For Ad 7 and Ad 11 sub-genome typing, we used Taq I and Hinf I that recognize 4- or 5-base pair sequences.

Results: The 13 Ad 7 strains all belonged to the same genome type and sub-genome type (Ad 7dH1T1). Adenovirus type 11 strains showed six genome types, with Ad 11p being the most frequent strain. Fifteen Ad 11p strains showed three sub-genome types, but none was the same as the prototype.

Conclusions: Adenovirus type 7 seemed quite stable and an epidemic may occur again. On the other hand, Ad 11 showed several different types. This finding suggests that Ad 11 did not cause an epidemic in Japan during the first half of the 1990s.

Introduction

Of the human adenoviruses (Ad) belonging to the B subgenera, it is known that Ad types 3, 7, and 11 cause conjunctivitis. Adenovirus type 3 and Ad 7, which belong to the B1 group, cause inflammation of the upper respiratory tract and pneumonia in addition to conjunctivitis, while Ad 11, which belongs to Group B2, causes diseases such as cystitis and nephritis. Over the last 10 years in Japan, Ad 3 has been the most frequently isolated.¹ On the other hand, Ad 7 and Ad 11 received attention in the latter half of the 1950s as the causative agents in epidemic keratoconjunctivitis (EKC) and pharyngoconjunctival fever (PCF).2, 3 Only a few adenoviruses have been isolated in Japan in the past 10 or more years. However, Ad 7 attained high frequencies of isolation beginning in early 1995 and is now receiving attention as an Ad that causes recurrent infection.⁴ There was also a report⁵ that Ad 11 was the cause of a large-scale epidemic of conjunctivitis in Southeast Asia in the 1980s.

Epidemiological analyses based on genome type differences have been conducted in recent years. Various genome types circulated in certain countries and continents in different years and caused outbreaks with varying degrees of severity. Wadell et al⁶ classified Ad 7 into Ad 7p and 7a to 7f genome types based on the differences in the cleavage patterns obtained with restriction endonucleases (REs) that recognize 6-base pair sequence. Adenovirus 7p is a genome type of prototype, of which a strain named Gomen was detected in throat swab abrasions of a patient with pharyngitis. They have described repeated outbreaks of Ad 7b in Europe, the United States, and Australia, and of Ad 7d in China, and reported that Ad 7b and Ad 7d were closely related because of the high percentage of identical restriction fragments. It was reported that the three strains isolated in Japan from 1969 to 1979 were Ad 7p.6, 7 The Ad 7 epidemic strains isolated in Japan since 1995 were classified as Ad 7d according to Wadell's classification. However, it has been reported that the cleavage pattern obtained with BstE II is different from the genome types reported thus far.4, 8 This genome type may be the same as the genome type of the strain isolated in Israel.⁹ Furthermore, Ad 7h, which has been reported to be an epidemic strain in South America,¹⁰ was isolated in Aichi prefecture, Japan, in 1996.¹¹ The majority of strains described in these reports were isolated from pharyngeal exudates. In the more than 100 strains isolated, only a few were isolated from conjunctival abrasions.4, 12 There are very few reports on Ad 7 from conjunctival abrasions in international literature even though it is recognized as being the causative agent in PCF.

Adenovirus type 11 has been classified into five genome types (Ad 11p, 11a to 11d) by Guo et al¹³ based on the differences in the cleavage patterns generated by REs which recognize 6-base pair sequence. Adenovirus 11p is a genome type of prototype, in which the strain named Slobitski was detected in the stool of a patient with paralytic polio. There have been several reports in Japan on the isolation of strains from conjunctivitis abrasions and genome types. In these reports, the majority of genome types are Ad 11p. Multitype genome types also have been reported.14, 15, 16

In the present study, we conducted an epidemiological examination of the genome types of strains isolated from the abrasions of Ad 7 conjunctivitis patients infected from 1995 onward, with prevalent recurrent infection, as well as the genome types of strains isolated from the abrasions of Ad 11 conjunctivitis, which until now has not been so prevalent in Japan. We also compared the clinical symptoms associated with these two types of conjunctivitis. Itakura et al¹⁷ and Shiao et al¹⁸ reported that they were able to classify not only the genome type, but also the sub-genome type of the same genome types by determining the differences in cleavage patterns using REs that recognize 4- or 5-base pair sequences, and that they could predict the stability of the genome type. We also studied the sub-genome types of strains that expressed the same genome type to monitor the alterations occurring in prevalent strains.