Page 239 - Avian Virology: Current Research and Future Trends

232 | Yao and Nair

transmissibility of avian sarcomas. In 1909, he succeeded in More detailed reviews of the history of avian retrovirus
transplanting a spindle cell sarcoma from one hen to another research are available elsewhere (Payne, 1992, 1998; Vogt, 2010;
(Rous, 1910) and soon after showed that the transplantable Rubin, 2011; Weiss and Vogt, 2011; Payne and Nair, 2012; Nair
tumour could be transmitted by cell-free filtrates (Rous, 1911). and Fadly, 2013).
Over the next 2 decades, some 20 transplantable tumours of
fowl were shown by a number of workers to be filterable (Claude
and Murphy, 1933). In the 1920s and 1930s, many transmission Infectious agent
studies were also conducted on the avian leukoses by notable
workers including Furth (1933) in the USA, Jármai (1933) Classification
in Hungary, Engelbreth-Holm (Engelbreth-Holm, 1931/2; Viruses of the avian leukosis/sarcoma group (ALSV) are placed
Engelbreth-Holm and Rothe-Meyer, 1932) in Denmark, and in the genus Alpharetrovirus of the family Retroviridae (http://
Oberling and Guérin (1933) in France, and numerous strains ictvonline.org/virusTaxonomy.asp?version=2009&bhcp=1).
of avian leukosis virus were isolated (Burmester and Purchase, ALV is the type species of the genus, with other species include
1979). An important question was whether the same or differ- viruses such as Rous sarcoma virus (RSV) and a number of
ent agents caused the 3 forms of leukosis. In general, erythroid replication defective viruses. In common with other members
and myeloid leukosis were readily transmissible, either in pure of this RNA virus family, ALVs are characterized by the unique
or mixed forms, lymphoid leukosis was not. Furth provided possession of the enzyme reverse transcriptase that drives the
evidence of transmission of lymphoid leukosis with filtrates generation of the DNA provirus which is integrated into the host
(Furth, 1933), and conclusive proof of the viral aetiology of genome during viral replication.
this form came from transmission experiments of Burmester
and his co-workers in 1946–1947 (Burmester, 1947; Burmester Morphology
and Cottral, 1947; Burmester and Denington, 1947).
Much of the early research on avian leukosis and sarcomas Ultrastructure
was motivated by basic scientific and medical interests. From In thin-section electron microscopy, avian leukosis/sarcoma
1920–1940, however, the expansion of the poultry industry in the viruses (ALSV) have an inner, centrally located electron-dense
USA and elsewhere brought increasing losses from the so-called core about 35–45 nm in diameter, an intermediate membrane,
‘avian leukosis complex’. Research was carried out particularly and an outer membrane. This appearance typifies the C-type
at land-grant colleges and state agricultural stations in the USA, retroviral morphology. The overall diameter of the virus parti-
with the aim being practical control of these diseases (Burmester cle is 80–120 nm, with an average of 90 nm. Immature virions
and Purchase, 1979). The disease picture was complicated by the budding from the cell membrane can be visualized. Negatively
inclusion in the leukosis complex of neurolymphomatosis (range stained preparations reveal essentially spherical particles that
or fowl paralysis), and visceral lymphomas associated with this are readily distorted under certain conditions of drying (Beard,
disease, which were increasing in prevalence. There was much 1973). Characteristic knobbed spikes about 8 nm in diameter are
uncertainty and argument whether or not neurolymphomatosis present on the surface of the particles and comprise the viral
(now termed Marek’s disease) was caused by the agents that envelope glycoproteins. These projections can also be seen in
caused the leukoses (Payne, 1985). The use of the term ‘visceral thin sections. By filtration through membranes of graded pore
lymphomatosis’ (Jungherr, 1941) to cover both lymphoid leu- size, ultracentrifugation, and electron microscopy, viruses have
kosis and lymphomas associated with neurolymphomatosis did been shown to have a diameter of 80–145 nm. The value of
not help the debate (Biggs, 1961; Campbell, 1961). In 1939, the 1.15–1.17 g/ml for the buoyant density in sucrose is characteris-
US Department of Agriculture established the Regional Poultry tic for C-type retroviruses (Robinson and Duesberg, 1968; Bates
Research Laboratory at East Lansing, Michigan (later renamed as et al., 1993).
the Avian Disease and Oncology Laboratory) to study the cause
and control of fowl paralysis and other neoplastic conditions.
In 1959, a similar centre, the Leukosis Experimental Unit of the Genome structure and organization
Houghton Poultry Research Station, was established in England. Structurally, ALVs are simple viruses with a viral genome of
Numerous other solid tumours have been associated with about 7.3 kb in length. From the 5′ end to the 3′ end of the viral
the avian leukoses occurring in the field and in transmission genome, the genes gag/pro-pol-env, which encode the proteins of
experiments, including connective tissue tumours, nephromas the virion group-specific (gs) antigens and protease, the enzyme
and nephroblastomas, endothelial tumours, neural tumours and reverse transcriptase, and the envelope glycoproteins respectively.
various other epithelial tumours (Beard, 1980; Fadly and Payne, These structural genes are flanked by genomic sequences associ-
2003). Also included in the avian leukosis complex is a hyper- ated with the regulation of viral replication, which in the DNA
trophic bone disorder osteopetrosis, first reported by Pugh in 1927 provirus form the viral long terminal repeats (LTRs) which
(Pugh, 1927) and described and reproduced in 1938 by Jungherr carry promoter and enhancer sequences. Viral integration in a
and Landauer (1938). The latter workers, and later Burmester and genomic locus could potentially lead to the activation of the cel-
co-workers (Burmester, 1947; Fredrickson et al., 1965), noted the lular oncogene (e.g. c-myc in LL) adjacent to the integration of
association of osteopetrosis with lymphoid leukosis. ALV provirus through the mechanism of insertional mutagenesis