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decrease by 5 dpi but reach nearly the same levels of uninfected al., 2016a). In contrast, mortalities in SPF layers were 20% and
controls after this time point. In spleen, IFN-α mRNA is up- 8% when infected with the same isolates in species FAdV-E and
regulated at 7 dpi, whilst IFNγ mRNA levels significantly increase FAdV-D, respectively (Matos et al., 2016a).
at 5 and 7 dpi. IL-12 mRNA increases at 3, 5 and 7 dpi and decline Despite their ability to induce neutralizing antibodies, avian
by 14 dpi. Expression levels of these cytokines, except IL-10, adenoviruses – such as HEV and FAdV-1, 4 and 8 – have evolved
significantly increase in bursa of Fabricius of infected chickens mechanisms of immune evasion that have negative effects in the
at 5, 7 and 14 dpi. Levels of IL-10 mRNA, on the other hand, antibody response (see section ‘Mechanisms of immune evasion:
remain unchanged by 14 dpi, time by which its levels significantly latent and persistent infections and immunosuppression’).
decrease (Deng et al., 2013).
The mechanisms whereby FAdVs or other avian adenovi- Cellular immune response
ruses activate cytokine expression are unknown. Recent studies Cell-mediated immunity to avian adenoviruses seems to play
suggest the role of FAdV-9 dUTPase in the induction of type I important roles in virus clearance (Umesh Kumar et al., 1989;
and II IFNs, cytokines (IL-8 and IL-10) and antibody response Rautenschlein and Sharma, 2000; Schonewille et al., 2010).
(Deng et al., 2016, 2017). Cytokine expression determined by the Indeed, vaccination with live-attenuated FAdV-4 protects SPF
viral dUTPase seems to be also tissue-and cell type-dependent. chickens from FAdV-4-induced HS in the absence of neutralizing
For example, IFN-α and IFNγ are significantly up-regulated antibodies (Schonewille et al., 2010).
in spleen of chickens infected with wild-type FAdV-9, while Chickens infected with either FAdV-1 or EDSV have a signifi-
expression levels of these cytokines were significantly lower in cant increase in the overall T-lymphocyte population as early as
birds infected with dUTPase-negative mutant virus. Type I IFNs 1 week p.i. and continues up to 5 weeks p.i. (Umesh Kumar et al.,
(IFN-α and IFN-β) and IL-10 were significantly up-regulated 1989; Lal et al., 1991). Detailed studies show that fluctuations in
and down-regulated in liver from birds infected with wild type the T-cell populations are virus serotype-and tissue-type depend-
and dUTPase-negative virus, respectively. Except for IFN-β, up- ent. For example, infections of SPF chickens with FAdV-8 increase
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regulated upon infection with wild type virus, expression of the CD3 , CD4 and CD8 T-lymphocytes at 25 dpi in the thymus.
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analysed cytokines did not seem to significantly change in caecal In the spleen, CD3 and CD4 population increases, while CD8
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tonsils (Deng et al., 2017). and γ δ T lymphocytes decrease at 30 dpi. In peripheral blood,
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Cytokines expressed upon virus infection seem to correlate γ δ T-cells decrease while CD3 , CD4 and CD8 cells increase
with virus-induced pathogenesis, as is the case of HEV. HEV (Wang et al., 2012).
induces type I and II IFNs as well as pro-inflammatory cytokines Infection with virulent FAdV-4 isolate (AG234) causes a
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such as IL-6 and TNF-α. IFNs seem to play protective roles decrease of CD3 , CD4 and CD8 T-cells in the spleen. This is
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against HE, whilst induction of high levels of TNF-α correlates accompanied by a decrease of CD4 and CD8 T-lymphocytes in
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with severe intestinal lesions. Induction of ‘cytokine storm’ by the thymus and CD3 cells in spleen (Schonewille et al., 2008).
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HEV infection seems to lead to a systemic shock with multiple HEV infection decreases IgM B cells and increase CD4 cells
organ failure and death (Rautenschlein and Sharma, 2000). in the spleen resulting in an alteration of the CD4 :CD8 ratio.
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Increase in CD8 cells is observed at 16 dpi and seems to be asso-
Humoral immune response ciated with virus clearance. Studies have shown that treatment
In general, birds infected with avian adenoviruses develop of turkeys with cyclosporin A (CsA) selectively impair T-cell
type-specific neutralizing antibodies that are detectable from mitogenesis and protect the birds against HEV-induced intestinal
one week after infection and antibodies levels peak by 3 weeks. haemorrhages, suggesting a role of T-cells on HE (Suresh and
Virus excretion often correlates with the absence of neutraliz- Sharma, 1995).
ing antibodies, though excretion can still occur in the presence
of antibody (Smyth, 2013). Maternal antibodies are usually Mechanisms of immune evasion: latent and
detected in chicks at 2 to 4 weeks after hatching. persistent infections and immunosuppression
Some studies suggest that virus excretion and antibody Some avian adenoviruses are non-pathogenic, others are asso-
production may differ among chicken breeds. White leghorn ciated with economically important diseases in poultry. For
chickens seem to have stronger antibody response to FAdV-9 successful replication, viruses have to overcome host defence
than Barred Rock chickens (Ojkic and Nagy, 2003; Corredor barriers including antimicrobial peptides (defensins), innate
and Nagy, 2010a, 2011; Deng et al., 2013). Similar observations immunity in the respiratory and gastrointestinal tracts, etc. As
are reported for experimentally infected SPF Rhode Island Red mentioned in a previous section (see ‘Effects on the host cell,
pullets and non-SPF ISA brown pullets with ESDV (Smyth et al., signalling pathways and apoptosis’), adenoviruses modulate and
1988). These observations seem to correlate with recent studies evade the host’s immune response through various mechanisms
demonstrating the association between genetic background of the that are mediated by mostly early viral genes. Immune evasion
host and virus-induced pathogenesis. Infection of specific patho- can result in latent or persistent infections, which are common
gen free (SPF) broilers with European field isolates belonging infections in poultry, even in SPF chickens (Girshick et al., 1980;
to species FAdV-E (FAdV-7, -8a and -8b) and FAdV-D (FAdV-2 McFerran and Smyth, 2000). Antibodies may not be detected
and -11), previously found in IBH outbreaks (Schachner et al., during in ovo infection, likely due to latency (Smyth, 2013).
2016), caused 100% and 96% mortality, respectively (Matos et The mechanisms involved in the establishment of latency