Page 241 - Avian Virology: Current Research and Future Trends

234 | Yao and Nair

1 (chNHE1) protein (Chai and Bates, 2006; Ning et al., 2012). Defectiveness and phenotypic mixing
Chicken Annexin A2 (chANXA2) has been recently described as A number of avian retroviruses have been shown to have defective
a novel receptor for ALV-J using a DF1 cell line expressed viral genomes and arise either spontaneously or as a result of experi-
receptor-binding protein (Mei et al., 2015). mental mutagenesis (Hayward and Neel, 1981; Maeda et al.,
2008). Some viruses (certain strains of RSV and acute leukaemia
Synthesis and integration of viral DNA viruses) are defective for genes required for replication and are
Detailed reviews on the synthesis and integration of viral DNA termed replication-defective (rd) mutants. They will transform
have been provided elsewhere (Brown, 1997; Cherepanov et cells but require the presence of a helper leukosis virus to enable
al., 2011; Li et al., 2011). Major stages in formation of retroviral them to replicate (e.g. BH-RSV and AMV lack the env gene, and
DNA are (1) synthesis of the first (minus) strand of viral DNA by AEV and MC29 lack the pol and env genes).
reverse transcription of viral RNA by reverse transcriptase, form-
ing an RNA:DNA hybrid; (2) removal of RNA from the hybrid
by RNase-H and formation on the template of minus-strand DNA Avian leukosis virus envelope subgroups
of second (plus) strands of viral DNA, giving rise to linear DNA The ALVs can be classified as endogenous (e.g. subgroup E) or
duplexes (these duplex molecules are detectable in cytoplasm exogenous viruses according to their mode of transmission. Exog-
of the cell within a few hours of infection); and (3) migration of enous ALVs from chickens can be classified into five subgroups
linear DNA to the cell nucleus. (A, B, C, D and J), on the basis of differences in the viral envelopes
Linear viral DNA becomes linearly integrated into the host which affect antigenicity, as determined by induction of virus
DNA under the influence of the enzyme integrase. This integra- neutralizing antibodies, host range, and ability to interfere with
tion can occur at many sites, and infected cells can contain up infection by other ALVs of the same or differing subgroups. The F,
to 20 copies of viral DNA. The proviral genes occur in the same G, H and I subgroups of ALV are found in ring-necked and golden
order as their RNA copies occur in the virion, and they are flanked pheasants, Hungarian partridge and Gambel’s quail, respectively.
on either side by identical sequences of nucleotides – the long ter- Subgroup E ALV are endogenous retroviruses and are not consid-
minal repeats (LTRs). These are composed of repeated sequences ered pathogenic. There have been recent reports on the isolation
derived from terminal regions of viral RNA and include promoter of a new ALV subgroup K from chickens in China, although the
and enhancer sequences controlling transcription of viral DNA to subgroup status of the viruses needs to be confirmed (Wang et al.,
RNA. The LTR promoters may also cause abnormal transcription 2012; Li et al., 2016). Viruses of subgroups A, B, C, D and J are
of host genes usually downstream of the proviral DNA, leading to oncogenic, causing mainly lymphoid leukosis (subgroups A and
oncogenesis. B) or myeloid leukosis (subgroup J). Viruses within a subgroup
usually cross-neutralize to varying extents, although antigenic
Transcription variants of subgroup J ALV exist which do not cross-neutralize.
Formation of new virions in the infected cell is the result of tran- A partial cross-neutralization occurs between subgroup B and D
scription and translation of proviral DNA, the major events being viruses, but otherwise viruses in the different subgroups do not
as follows: cross-neutralize each other.
Strains of ALSV can also be placed into two major classes in
1 Transcription of viral RNA on a template of proviral DNA respect of rapidity of induction of tumours:
under the influence of a host RNA polymerase. Transcription
of the pro sequence of the gag/pro gene to produce protease 1 Acutely transforming viruses. The acutely transforming viruses
(PR) involves a frame shift. Viral RNA molecules give rise are those that carry viral oncogenes in their genome. These
to mRNA in association with polyribosomes, and they also viruses can induce neoplastic transformation, in vivo or in
serve as genomic RNA in newly formed virions. New viral vitro, within a few days or weeks. Depending on the oncogene
RNA is detectable within 24 hours of infection. possessed by the virus, acutely transforming ALVs induce
2 mRNA species, bound to polyribosomes, are translated to different types of neoplasms, for example v-myc: myeloid
form the gag, pol, and env gene-coded proteins that compose leukosis (myelocytoma); v-myb: myeloid leukosis (myelo-
the virion. The gag-pol gene product is a large protein precur- blastosis); v-erbB: erythroid leukosis; v-src: sarcoma; v-fps:
sor (180 kDa) Pr180, which is cleaved to give a precursor fibrosarcoma (Graf and Beug, 1978; Enrietto and Wyke,
polyprotein Pr76 (76 kDa) from which virion core proteins 1983; Enrietto and Hayman, 1987; Moscovici and Gazzolo,
MA (p19), CA (p27), NC (p12), PR (p15) and p10 are 1987; Kung and Liu, 1997; Chesters et al., 2001; Wang et al.,
derived. The Pr180 polyprotein also gives rise to RT (p63 2016a–c). Such ALVs are termed ‘acutely transforming’, and
and p95) and integrase (IN, p32) enzymes. The env gene neoplastic cells are induced within a few days after infection.
product is a precursor protein gPr92 (92 kDa) from which 2 Slowly transforming viruses. These ALVs do not carry viral
the viral envelope proteins SU (gp85) and TM (gp37) are oncogenes. They induce tumours by insertional activation
derived. Translation of env is from a spliced subgenomic of a cellular proto-oncogene to bring about neoplastic trans-
RNA. The viral proteins localize at the plasma membrane formation. Development of tumours over many weeks or
of the cell, where crescent-shaped structures develop and months (Enrietto and Wyke, 1983; Coffin et al., 1997; Kung
virions that bud off from the cell may be visualized. and Liu, 1997; Nair, 2008; Fan and Johnson, 2011).