Page 305 - Avian Virology: Current Research and Future Trends

296 | Corredor and Nagy

adenoviruses. However, the fibre gene – located near the right and organization. For example, the genome of aviadenoviruses is
end in mastedenoviruses, aviadenoviruses, atadenoviruses and generally 10 kb larger (43–45 kb) than that of mastadenoviruses,
siadenoviruses – maps at the left end region of the genome of the with most early gene content at the right ends. In contrast, avian
ichtadenovirus (Harrach et al., 2011). adenoviruses such as EDSV (genus Atadenovirus) and HEV
E genes are clustered into regions (E1–E4 in mastadenovi- (genus Siadenovirus) have smaller genomes (33.2 and 26.3 kb,
ruses) that can be located centrally at the minus strand (E2 genes) respectively) and lower gene content with respect to those of
or at the left and right end of the genome (E1, E3 and E4). mastadenoviruses and aviadenoviruses (Hess et al., 1997; Pitcov-
Mastadenovirus E1, E3 and E4 genes lack nucleotide sequence ski et al., 1998).
homology to those of aviadenoviruses, atadenoviruses and siad-
enoviruses. Aviadenovirus genome
The early region at the left end of the genomes of avian The genomes of aviadenoviruses are the largest among all avian
adenoviruses – equivalent to the E1 locus in mastadenoviruses adenoviruses, and size ranges from 43 to 45 kb. Except for E2 and
– is located between the left end ITR and IVa2 gene (an inter- L genes, the function of most genes at both ends is unknown. Avi-
mediate gene). Open reading frames (ORFs) within this region adenovirus genomes such as those of FAdV-1, FAdV-8, FAdV-9
have rightward and leftward orientations in aviadenoviruses and and FAdV-10 contain non-essential regions at both ends that
atadenoviruses, whilst all ORFs are rightward-oriented in sia- make them suitable for development of recombinant vaccines or
denoviruses. One or more early gene clusters are located at the gene delivery vectors into avian and mammalian cells (Corredor
right end of the genomes. Siadenoviruses have an E gene cluster and Nagy, 2010b; Johnson et al., 2003; Francois et al., 2004; Pei et
between the pVIII gene and U exon, which is equivalent to the al., 2015, 2018; Corredor et al., 2017).
location of the E3 region of mastadenoviruses. Atadenoviruses
and aviadenoviruses, on the other hand, lack this E3 region. The Left end region
last E gene cluster – equivalent to mastadenovirus E4 – maps In general, gene content and organization of the left end region
downstream the fibre gene in all avian adenovirus genomes and is conserved among aviadenoviruses (Table 10.2). This region
its gene content and length vary among members (Table 10.2) consists of two main clusters of ORFs with rightward (ORFs
(Wold and Ison, 2013). 0, 1, 1A, 1B, 1C and 2) and leftward (ORFs 24, 14, 13 and 12)
Regardless of function, transcriptional unit and nucleotide orientations (Davison et al., 2003; Corredor et al., 2006). Dele-
sequence homology, viral genes are classified into two groups: tion mutant FAdV-9 virus lacking the rightward ORFs is viable
genus-common and genus-specific genes (Davison et al., 2003). in vitro, but deficient to replicate in vivo (Corredor and Nagy,
Genus-common genes (IVa2, E2 and L genes) map centrally 2010a). Transcription of these ORFs in FAdV-9 has been demon-
in the genome and are conserved among all members of the strated (Cao et al., 1998; Ojkic et al., 2002), and the function of
family Adenoviridae, suggesting a common ancestral adenovirus ORF1 – encoding the viral dUTPase – has been explored (Deng
(Davison et al., 2003). The E2 region consists of genes encod- et al., 2016, 2017). Transcription of rightward ORFs seems to be
ing the viral DNA polymerase, pTP and DBP. IX (present only under the control of a common promoter upstream of ORF0.
in mastadenoviruses) and IVa2 (present in all adenoviruses) Transcription of leftward ORFs such as ORF13 of FAdV-1 and
are intermediate genes expressed shortly after DNA replication FAdV-9 seems to be under the control of the E2 promoter (Payet
(Huang et al., 2003; Parks, 2005). Gene IVa2 maps downstream et al., 1998; Ojkic et al., 2002). The E2 promoter is also known
of the IX gene in mastadenoviruses, ORF12 in aviadenoviruses, to activate the transcription of the viral DNA polymerase, DNA-
E1B 55k in atadenoviruses and the highly hydrophobic protein binding protein and pre-terminal protein (Wold and Ison, 2013).
ORF in siadenoviruses. IVa2 plays various roles during virus rep- Homologues to ORFs 1, 2 (parvovirus NS-1-like protein),
lication including virus assembly and transcriptional activation 14 and 12 are present in all aviadenoviruses sequenced to date
of the major late promoter by direct binding (Huang et al., 2003; (Table 10.2). The absence or presence of additional ORFs
Pardo-Mateos and Young, 2004). The L region consists of genes with differences in orientation and arrangement seems to be
arranged in the following order (5′ to 3′ in the plus strand): 52k, species-specific. For example, ORF0 is present in FAdV and
pIIIa, III, pX, pVI, V (present only in mastadenovirus), hexon, TAdV species, whilst absent in GoAdV-A (GoAdV-4), PiAdV-A
protease, 100k, 22k, 33k, pVIII, U-exon (UXP in mastadeno- (PiAdV-1) and DAdV-B (DAdV-2); ORF1C, a homologue to
virus) and fibre (two fibre genes in some aviadenoviruses, see bovine papillomavirus E5 gene (Ojkic and Nagy, 2000; Corredor
section ‘Morphology and virus structure’). et al., 2006; Marek et al., 2013), is absent in DAdV-B (DAdV-2),
Genus-specific genes map at the left and right ends and are FAdV-B (FAdV-5), FAdV-C (FAdV-4 and FAdV-10) and PiAdV-A
generally expressed early in infection (Chiocca et al., 1996; Ojkic (PiAdV-1); four ORF14 homologues (ORFs 14, 14A, 14B and
and Nagy, 2000; Davison et al., 2003; Harrach et al., 2011). These 14C) are present in FAdV-C (FAdV-4 and -10); ORFs 0, 1A, 1B
genes lack nucleotide sequence homology among genera and are and 1C are absent in PiAdV-A (PiAdV-1) and DAdV-B (DAdV-2)
mainly involved in the modulation of the host’s immune response, (Marek et al., 2014a); ORF-52 is leftward-oriented and located
cell cycle progression and regulation of apoptosis (Davison et al., between ORFs 1 and 2 of PiAdV-A (PiAdV-1), whilst this homo-
2003). Genus-specific genes vary in content and arrangement logue is rightward-oriented and located between ORFs 1 and
(Table 10.2). Gene content seems to determine the genome size 1A of GoAdV-A (GoAdV-4) and upstream ORF1 of DAdV-B