Genomic sequence and analysis of a vaccinia virus isolate from a patient with a smallpox vaccine-related complication
Date
2006-10-25
Authors
Li, Guiyun
Chen, Nanhai
Feng, Zehua
Buller, R Mark L
Osborne, John
Harms, Tiara
Damon, Inger
Upton, Chris
Esteban, David J
Journal Title
Journal ISSN
Volume Title
Publisher
BioMed Central
Abstract
Background: Vaccinia virus (VACV)-DUKE was isolated from a lesion on a 54 year old female
who presented to a doctor at the Duke University Medical Center. She was diagnosed with
progressive vaccinia and treated with vaccinia immune globulin. The availability of the VACV-DUKE
genome sequence permits a first time genomic comparison of a VACV isolate associated with a
smallpox vaccine complication with the sequence of culture-derived clonal isolates of the Dryvax
vaccine.
Results: This study showed that VACV-DUKE is most similar to VACV-ACAM2000 and
CLONE3, two VACV clones isolated from the Dryvax® vaccine stock confirming VACV-DUKE as
an isolate from Dryvax®. However, VACV-DUKE is unique because it is, to date, the only Dryvax®
clone isolated from a patient experiencing a vaccine-associated complication. The 199,960 bp
VACV-DUKE genome encodes 225 open reading frames, including 178 intact genes and 47 gene
fragments. Between VACV-DUKE and the other Dryvax® isolates, the major genomic differences
are in fragmentation of the ankyrin-like, and kelch-like genes, presence of a full-length Interferon-
α/β receptor gene, and the absence of a duplication of 12 ORFs in the inverted terminal repeat.
Excluding this region, the DNA sequence of VACV-DUKE differs from the other two Dryvax®
isolates by less than 0.4%. DNA sequencing also indicated that there was little heterogeneity in the
sample, supporting the hypothesis that virus from an individual lesion is clonal in origin despite the
fact that the vaccine is a mixed population.
Conclusion: Virus in lesions that result from progressive vaccinia following vaccination with
Dryvax are likely clonal in origin. The genomic sequence of VACV-DUKE is overall very similar to
that of Dryvax® cell culture-derived clonal isolates. Furthermore, with the sequences of multiple
clones from Dryvax® we can begin to appreciate the diversity of the viral population in the smallpox
vaccin
Description
BioMed Central
Keywords
Citation
Li et al. Genomic sequence and analysis of a vaccinia virus isolate from a patient with a smallpox vaccine-related complication. Virology Journal 2006, 3:88