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XCXC BC3
HAdV-5 L--HCHCSSPGSLQCIAGGQVLASWFRMVVDGAM--------
HAdV-9 L--HCHCSSPGSLQCRAGGTLLAVWFRRVIYGCM--------
HAdV-12 I--HCHCQRPGSLQCMSAGMLLGRWFKMAVYGAL--------
FAdV-4_ORF14B LYSHCRCKDPYSLFCRALNQYVAQQWRLDVREHL--------
FAdV-10_ORF14B LYSHCRCKDPYSLFCRALNQYVAQQWRLDVREHLASVPIRHP
PiAdV-1_ORF14A VSYRCSCPSPHSLFCWSLAHYAVQYWINDVLEYL--------
FAdV-4_ORF14A LKYRCTCPKPHSLFCHSLRMKTYIRWVDEIRATT--------
FAdV-10_ORF14A LKYKCTCPKPHSLFCHSIRMKAYTRWVDEIRATT--------
DAdV-2_ORF14 VLYSCKCHDKLSLQCMSRVHVLTAMWMDCIHAYL--------
TAdV-1_ORF14 VLYYCACRDPRSLQCLALAHVFTQYWRDCIVRYV--------
TAdV-1_ORF24 CIYECTCHRPRSLQCSAMASVVIQHWHAEIRRYL--------
FAdV-4_ORF14 VKLRCNCGDGNSLFCQSLRELLFHSWKEAIQNGV--------
FAdV-10_ORF14 VKLRCNCGDGNSLFCQSLRELLFHSWKEAIQNGV--------
FAdV-4_ORF24 IRSECSCRMPHSLFCESLGQLVFTYWFETIQEFI--------
FAdV-10_ORF24 IRSECSCGMPHSLFCESLGQLVFAYWFETIQEFI--------
FAdV-1_ORF14 IQYICSCETPRSLFCLSLIRVLTAHWAKTVVNFV--------
TAdV-5_ORF14 ITYCCQCDNPKSLFCQSLMHVLFRHWSRLIVDFV--------
FAdV-2_ORF14 ASYVCECEEPLSLFCQSLAVTLTMEWHAKLTAYPIAENPFP-
FAdV-9_ORF14 ASYVCECEEPLSLFCQSLAATLTMEWHAKLTAYP--------
FAdV-5_ORF14 AEYSCQCPEPLSLFCQSLASLLATQWYQRLLKNP--------
TAdV-4_ORF14 VSYSCNCDEPMSLFCQSLVAVLTQKWFDDLQSQS--------
FAdV-2_ORF24 IRYDCTCTNPYSLMCQAASKVVCTYWLDKVYEYF--------
FAdV-9_ORF24 IRYDCTCTNPYSLMCQAASKVVCTYWLDKVYEYF--------
TAdV-8_ORF24 VRYDCTCLNPFSLMCQSASKVICTYWLDQVQEYF--------
TAdV-4_ORF14A IRYDCNCSKPYSLMCQSTSKVVCTYWLDQVQSYF--------
FAdV-5_ORF14A VRYDCNCDKPHSLMCQSTCKVVVAYWLETVQEYF--------
GoAdV-4_ORF14 LAYACNCSNPLSLMCMSRLHVIVKRWTEMLKTVV--------
PiAdV-1_ORF14 IQVVCDCQQPGSVLCECILTLALERWAVRLLRAV--------

Figure 2. Human adenovirus E4ORF6-like sequence found in
Figure 10.2 Human adenovirus E4ORF6-like sequence found in aviadenoviruses. Amended from Gilson T, Blanchette P, Ballmann M Z,
aviadenoviruses. From Gilson T, Blanchette P, Ballmann M Z, Papp
Papp T, Pénzes J J, Benko M, Harrach B, Branton P E. (2016) J. Virol. 90: 7350–7367, with permission from the American Society for
Microbiology. T, Pénzes J J, Benko M, Harrach B, Branton P E. J. Virol. 90:
7350-7367, with modifications.

FAdV-1 Gam-1 or mastadenovirus E1A 19 K are functionally polymerase and pTP form a heterodimeric complex that binds
equivalent to Bcl2 protein in terms of inhibition of Bak- and Bax- to domain A of the origin of replication in both parental DNA
mediated apoptosis preventing the formation of Bak-Bax pores of strands. Cellular proteins NF1 and OCT1 physically interact
the outer mitochondrial membranes and release of cytochrome with the viral DNA polymerase and pTP, respectively. Bind-
c and Smac/DIABLO (Chiocca et al., 1997; Berk, 2013). Both ing of NF1 to the viral DNA polymerase is stimulated by the
E1B 19 K and Gam-1 also inhibit TNF-α signalling (Chiocca et viral DBP. These protein complexes bound to the origin of
al., 1997). replication in the viral genome gives rise to the preinitiation
E2 genes encode proteins for viral DNA replication including complex. The priming reaction takes place by the formation
the DNA polymerase, double-stranded DNA-binding protein of the pTP-deoxycytidine monophosphate (dCMP) complex
(DBP) and pre-terminal protein (pTP) (Berk, 2013). The acti- that is catalysed by the viral DNA polymerase. The pTP-dCMP
vation of E2 genes in avian adenoviruses is not well understood, primes the synthesis of the nascent DNA daughter strand by the
while their activation in mastadenoviruses is mediated by E1A viral DNA polymerase. The elongation of the daughter strand
and E4ORF6/7 proteins (Swaminathan and Thimmapaya, involves separation of the viral DNA polymerase from pTP,
1996). FAdV-1 Gam-1 and ORF22 protein, which are function- which remains covalently attached to the 5′ end of both termini.
ally equivalent to mastadenovirus E1A proteins, probably activate The elongation of the daughter strand requires DBP to unwind
E2 genes. the viral genome during synthesis.
In general, replication of the viral DNA in mastadenoviruses Transcription of L genes from the major late promoter (MLP)
begins at 6 hours post infection (hpi) (Berk, 2013) or 12 hpi is significantly increased after DNA replication. Such genes are
in aviadenoviruses (Alexander et al., 1998). The inverted ter- grouped into five families (L1–L5) in mastadenoviruses or six
minal repeats at both termini are the origin of replication of families (L1–L6) in aviadenoviruses (Payet et al., 1998; Ojkic et
the viral genome. Replication of the viral DNA takes place in al., 2002). During the early stage of infection, the transcription
two stages (Fig. 10.3). First, one of the DNA strands serves of only the L1 mRNA encoding the 52/55 K protein takes place.
as template for the synthesis of the daughter strand while the After DNA replication, transcription from the MLP is processed
other strand is displaced. Second, the displaced single-stranded by differential utilization of poly A and splicing sites to give rise to
parental strand forms a ‘panhandle’ structure through annealing at least 14 distinct mRNAs. Splicing takes place from an untrans-
of the self-complementary termini. This structure is disrupted lated leader, which can be either tripartite in mastadenoviruses
as the synthesis of the daughter strand begins. The viral DNA and atadenoviruses or bipartite in aviadenoviruses (Fig. 10.4)