Biology Reference
In-Depth Information
Introduction
Since its first discovery in cottontail rabbits in the early 1930s, papil-
lomavirus, a small non-enveloped DNA virus, has been isolated from
the human, monkey, bovine, rabbit, deer, hamster, and so on. These
papillomaviruses have a highly species-specific host range and thus are
named together with the host animal name, e.g. cottontail rabbit
papillomavirus (CRPV). The viruses attracted a lot of attention because
they cause a variety of proliferating epithelial lesions, such as benign
papilloma, wart, condyloma, and carcinoma. However, detailed biolog-
ical studies of the viruses were greatly hampered, largely due to the
lack of a cell culture system for virus propagation, until the viral
genomes were molecularly cloned in the late 1970s. The cloning
allowed the standardization of viral reagents and provided sufficient
material to initiate systematic studies of these viruses.
2
Among them, bovine papillomavirus type 1 (BPV1), which causes
fibrosarcoma in cattle, had been studied most extensively, largely
owing to the introduction of an infectivity assay system (focus forma-
tion of transformed cells) using rodent cells. The molecular studies
provided us with a general understanding of the papillomavirus
genomic structure and gene functions.
2
The molecular cloning of human papillomavirus in the 1980s
(HPV6 and HPV11 from benign genital warts; HPV16 and HPV18
from cervical carcinoma biopsies) facilitated the biological and epi-
demiological studies and a systematic evaluation of various HPVs.
52,53
To date more than 100 genotypes (classified by DNA homology) have
been cloned and are grouped into mucosal and cutaneous types based
on the tissue tropism. Among the mucosal types, HPV16, 18, 31, 33,
35, 39, 45, 51, 52, 56, 58, 59, 66, 68 and 73 are believed to be asso-
ciated with cervical cancer, the second most frequent gynecological
malignancy in the world, and HPV16 accounts for 50% of the cases.
Morphological and chemical studies were conducted with BPV1
and HPV1 virions isolated from the clinical lesions.
2,4
The virion (with
a diameter of 55 nm) comprises an icosahedral non-enveloped protein
shell designated as capsid and a single copy of the 8 kb double-stranded
circular DNA genome contained within the capsid. The capsid con-
sists of major capsid protein L1 (mol. wt.: 55,000) and minor capsid