New genome type of adenovirus serotype 4 caused nosocomial infections associated with epidemic conjunctivitis in Japan

Abstract

Human adenovirus type 4 is one of the major serotypes isolated from patients with adenoviral conjunctivitis. In 2001 we encountered nosocomial infections with epidemic conjunctivitis in the ophthalmology ward of one hospital in Sapporo, which is in the northern part of Japan. Adenoviruses were isolated from the patients with this nosocomial infection and identified as adenovirus type 4 (AdV-4) by a neutralization test with serotype-specific antiserum. When the cleavage patterns of the isolates were compared with the full viral genome with BamHI and SmaI, the cleavage patterns of the isolates were shown to be different from those of AdV-4p and other previously known AdV-4 variants. The nucleotide sequences of the fiber gene of the isolates showed the highest homologies (94.3%) with AdV-4 among the nucleotide sequences available from GenBank and formed a monophyletic cluster along with the prototype strain of AdV-4. The isolates, however, were located in a different lineage from those of AdV-4p and the AdV-4 variant from the sporadic infections. We conclude that the nosocomial infection that appeared in 2001 was caused by a new genome type of AdV-4, which was designated AdV-4c.

FIG. 1.

Restriction patterns of AdV-4p, AdV-4a, and AdV-4c, the new variant associated with nosocomial infection. Lane M, molecular size markers, 2-log DNA ladder (New England Biolabs, Beverly, Mass.). Lane p, adenovirus type 4 prototype. Lane a, representative isolate (TC-4822/s-84) of AdV-4a. Lane c, representative isolate (TC-33376/s-01n) of AdV-4c. Arrowheads indicate bands present in AdV-4c but absent from AdV-4a or those present in AdV-4a but absent from AdV-4c.

FIG. 2.

Phylogenetic analysis of adenovirus prototype and clinical isolates of AdV-4 described in this study. The nucleotide sequence of the partial hexon gene (916 bp) was analyzed by the neighbor-joining method. Numbers at nodes are percentages of 1,000 bootstrap values. The following published sequences were used: AdV-2 (GenBank accession no. J01917), AdV-3 (X76549), AdV-4 (AB099380), AdV-5 (M73260), AdV-7 (AF065065), AdV-12 (X73487), AdV-16 (X74662), AdV-17 (AB099353), AdV-18 (Y17249), AdV-21 (AB053116), AdV-34 (AB052911), AdV-40 (L19443), AdV-41 (X51783), and AdV-48 (AB099377).

FIG. 3.

Phylogenetic analysis of isolates in this study and the AdV-4 prototype based on the fiber gene. The fiber gene of the new genome type (s-01, 01n/AdV-4v5) is located on another branch from that of the AdV-4a group. Numbers at nodes are percentages of 1,000 bootstrap values. The AdV-4p fiber gene sequence has been published (GenBank accession no. X76547).