Health life and viruses are way along aside any research and most important to observation in medical life and experments
THE Adenovirus group is a large and widespread family of viruses
infecting many species of the animal world. At the present time about
50 distinct antigenic types are known which can be isolated from man,
monkeys, cattle, mice, and dogs, and there is every reason to assume
that this list is far from complete. With a few exceptions, members of
this group do not produce overt disease in small laboratory animals
and their discovery was thus delayed until the advent of tissue culture
techniques
Knowledge of the Adenoviruses first came to light in the years 1953
when four independent groups of workers isolated agents producing
distinctive cytopathic effects in tissue culture. Rowe et al. in 1953
reported the isolation of 13 "adenoid degenerative agents" from naturally
degenerating cultures of hypertrophied tonsils and adenoids. A
few months later Hilleman et al} reported the isolation in HeLa cell
cultures of five identical agents from cases of acute respiratory disease
and primary atypical pneumonia in military recruits. They also showed
that some, at least, of the non-influenzal cases of respiratory disease
were associated with this new virus which they called "RI-67". The
third report of a new agent which was later shown to be an Adenovirus
came in 1954 from Neva and Enders. Their agent was isolated from a
case resembling Roseola Infantum in cultures of human kidney cells
These first three reports all came from the U.S.A. and were followed
later in 1954 by one from Scandinavia, when Kjellen5 announced the
isolation of nine agents from cases of pharyngitis, mesenteric lymphadenitis
and paralytic poliomyelitis. He showed that these agents were
related to RI-67 and the virus isolated by Neva and Enders
This work was soon followed by comprehensive reports showing that
the new viruses were aetiologically associated with upper respiratory
tract infections. Parrott et al. investigating an outbreak of febrile
pharyngitis and conjunctivitis coined the name pharyngoconjunctival
fever. At the same time, the same group classified the known agents
into six antigenic types and called them the Adenoidal-Pharyngeal
Conjunctival or A.P.C. viruses
Other groups of workers in America and Europe published work
associating the A.P.C. viruses with large outbreaks of acute respiratory
disease in military recruits. They also showed that the specific
disease recognised by the Commission on Acute Respiratory Diseases as
ARD was due to these viruses
The last of these early investigations resulted in the recognition of a
new type, from cases of epidemic keratoconjunctivitis, which Jawetz
et proved to be the sole type responsible for the widespread
outbreaks of this diseaseIn 1956 the name A.P.C. given to this group in 1954 was superseded by
the name Adenovirus with each member identified by a serotype
number, given on the results of neutralisation tests. Latterly haemagglutination
inhibition tests have also been used for identification and
at the time of writing there are twenty-eight recognised types infecting
humans, numbered 1 to Isolations of members of the Adenovirus
group have been made from monkeys,cattle,and mice,as well as
man, and the virus of infectious canine hepatitis has been related to this
group
The early observations of an absence of overt disease in small laboratory
animals has since proved to be incorrect, although at the present
time there is little evidence to show that the Adenoviruses affecting one
species infect members of any other species
Pereira and Kelly first reported that Adenovirus caused latent
infections in rabbits. Type 5, but not types 1, 2, 3 or 4, could be isolated
from the spleens of inoculated rabbits for at least two months after
infection although there were no overt signs of disease. More recently
there has been evidence of types 12 and 18 inducing the formation of
tumours when inoculated into the lungs of baby hamsters. However
for most work with Adenoviruses tissue cultures are required for
growth
HeLa cell cultures are most frequently used for the growth of the
members of this group but any epithelial cell culture can be used. The
human types all grow in HeLa, KB, HEp2, human amnion, humanthyroid, human embryo kidney and human embryo liver cell cultures,
but not all types are equally readily cultivated. Types
8, 9, 10, 12, 13, 18 to 28 are more difficult to grow than the others. The
poorest-growing type has proved to be type 8, in all cells except HEK
and HEL cultures.In this case it is not that infectious virus is not
produced in HeLa cells but that only a small proportion of the particles
can infect HeLa cells in comparison with the numbers which successfully
infect embryonic cells. Most of the human types can be adapted to grow
in monkey kidney cell cultures with varying ease, but these cultures are
not suitable for the initial isolation of Adenoviruses
Since their discovery a considerable amount of interest has been
directed towards the growth of these viruses. Much of the work has
been performed with types 1 to 8 using cover-slip preparations of HeLa
cells and occasionally other cells, and plaque-formation tests
Adenovirus adsorbs slowly to HeLa cells with 50% adsorption
occurring after 30-60 minutes for types 4 and 5. New virus first
appears intracellularly after 17-18 hours and only 6% at the most is
liberated into the medium after 6 days. For the release of all the virus
the cells must be disrupted. In this respect type 8 differs from the rest
all the new virus is liberated into the medium by the 5th day. With
types 4 and 5 approximately 10,000 PFU of virus are produced per
cell. One unusual feature with HeLa cells is the continuation of
metabolism which does not cease immediately following the production
of new virus. Furthermore cell glycolysis is stimulated resulting in an
increase in the amounts of lactic, pyruvic, acetic and a-ketoglutaric acids
produced
