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Chicken Infectious Anaemia Virus | 271

of the birds. In general haematocrit values < 27% are considered additional immune responses may play a role. However, there is
anaemic but can be as low as 4 to 10% in CAV-infected chickens no information available on the types of innate or cell-mediated
(Smyth et al., 1993). In addition to anaemia, affected chickens immune responses that were responsible for the recovery.
may become depressed with droopy wings, are reluctant to move
and often have a decreased body weight. Morbidity and mortality
typically start between 10 and 14 days of age and ends between Immunosuppression
26 and 35 days of age. Convalescent chickens may not reach
their target weights but appear otherwise healthy (Goryo et al., Impairment of innate immune responses
1987a; Yuasa et al., 1987; Vielitz and Landgraf, 1988; Chettle et It is widely accepted that clinical and subclinical CAV infections
al., 1989). Because CAV causes immunosuppression (see ‘Immu- reduce the number of T lymphocytes, heterophils and thrombo-
nosuppression’) chicks often are presented for post-mortem cytes (reviewed by Adair, 2000) and negatively affect the innate
examination with haemorrhagic syndrome (Yuasa et al., 1987) and acquired immune responses to pathogens and vaccinations
or with gangrenous dermatitis (Vielitz and Landgraf, 1988). The (reviewed by Schat and Skinner, 2014; Smyth and Schat, 2013).
latter is frequently referred to as blue-wing disease (Engström and Most of the studies on the effects on innate immune responses
Luthman, 1984). Clinical signs may occur in older birds with a were conducted prior to the identification and cloning of chicken
compromised humoral antibody response (see ‘Pathogenesis in cytokine genes. Adair et al. (1991) and McConnell et al. (1993a)
older chickens’). Gross lesions often include pale bone marrow, infected 1-day-old and 3-week-old SPF chickens, respectively.
severe thymus atrophy, and haemorrhages in the skeletal muscles Spleen cells were stimulated between 8 and 43 days pi with
and proventricular mucosa. Sometimes swollen and mottled liver Con-A. Production of ‘T-cell growth factor’ (probably IL-2) was
and bursa atrophy are seen, but those lesions may be caused by reduced at 8 and 15 days pi. Interferons were increased at 8 days pi
secondary infections (reviewed by Schat and Van Santen, 2013; and decreased afterwards until 43 days pi when interferon levels
Smyth and Schat, 2013). Histological examination of thymus were similar for spleen cell cultures from control and infected
tissue shows a depletion of cortex lymphocytes (Fig. 9.9) and the chickens. The mitogen response was also significantly reduced in
bone marrow shows aplasia and replacement of hemopoietic cells inoculated birds at 8 and 15 days. A similar reduction in mitogen
by fatty cells (Fig. 9.11). Detailed descriptions of histopathologic stimulation by CAV infection was reported by Bounous et al.
lesions can be found elsewhere (Schat and Van Santen, 2013; (1995). Using qRT-PCR assays Markowski-Grimsrud and Schat
Smyth and Schat, 2013). (2003) and Wani et al. (2016) found an increase in IFN-γ mRNA
between 5 and 10 days pi. However, a recent transcriptomic pro-
filing study did not confirm the increase of IFN-γ mRNA in the
Immune responses spleen but did find a significant increase in the bone marrow at 11
The finding that newly hatched chicks from antibody-positive days pi (Giotis et al., 2015). CAV infection also decreased IL-1
dams are protected against clinical disease (Yuasa et al., 1980a) production based on stimulation of thymocytes (McConnell et
indicated that maternal antibodies are important for protec- al., 1993a) and mRNA production (Wani et al., 2016), which was
tion against clinical disease. Longitudinal surveys of two broiler not confirmed by Markowski-Grimsrud and Schat (2003). The
breeder flocks showed that maternal antibodies could be detected transcriptome study suggests a more complicated picture with
up to 3 weeks of age using an indirect immunofluorescence significant increases in the thymus at 4 days pi and spleen at 7 days
test followed by seroconversion between 8 and 9 weeks of age pi, but a significant decrease in the thymus at 7 and 11 days pi
(McNulty et al., 1988). Otaki et al. (1992) found that chickens and at 4 days in the spleen. The results of the transcriptome study
were protected against challenge up to 3 weeks of age even when are in general confusing with significant increases and decreases
the dams had low VN antibody titres. Using qPCR and qRT-PCR reported for IL-4, IL-6, IL-10, IL-12, IL-13 and IFN-α and -β.
assays Markowski-Grimsrud and Schat (2003) demonstrated that However, the increases or decreases were not similar for the dif-
DNA copies were very low and that viral transcripts were absent ferent tissues and can be increased at day 4 in the thymus while
7 days pi in 4-week-old chickens which were positive for maternal decreased in the spleen at the same day. Clearly, additional studies
antibodies at 2 weeks of age. In contrast, hatch-mates lacking are needed to further understand the effects of CAV infection on
maternal antibodies had high levels of viral DNA and RNA. the regulation of cytokine expression.
Antibodies develop between 2 and 3 weeks pi of 1-day-old Macrophage functions were examined between 7 and 42 days
maternal antibody-free SPF chickens (Yuasa et al., 1983b; Imai et pi of 1- and 21-day-old SPF chickens (McConnell et al., 1993a,b).
al., 1999; Drén et al., 2000; van Santen et al., 2004a;). Antibody Fc receptor expression, phagocytosis and bactericidal activity
development was slower after oral challenge than parenteral chal- were all reduced between 7 and 42 days pi. Bounous et al. (1995)
lenge (van Santen et al., 2004a). Long-term studies in commercial noticed a decrease in natural killer cells at 18 and 25 days pi, but
breeder flocks and SPF flocks suggests that antibodies to CAV last Markowski-Grimsrud and Schat (2001) did not find an impair-
until at least 63 weeks of age (Imai et al., 1993; Schat and Schuk- ment of NK cell activity in CAV-infected chickens at 7 days pi.
ken, 2010). VN titres may decrease over time (Imai et al., 1993).
The observation by Hu et al. (1993a) that two embryonally Impairment of acquired immune responses
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bursectomized, CAV-infected birds recovered from low haemato- The loss of CD4 and CD8 cells in the thymus was discussed
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crit values in the absence of detectable antibodies suggests that in Pathogenesis in young chickens. CD4 and CD8 T-cells are