Page 24 - Avian Virology: Current Research and Future Trends

Avian Influenza Virus | 17

3 to 7 days depending on the virus isolate, age of the bird and et al., 2012; van de Sandt et al., 2012). Activation of the adaptive
bird species. Death may occur within 24 to 48 hours after the immune responses is mainly driven by antigen presenting cells
onset of symptoms, but it may be delayed for as long as 1 or 2 (APC), namely DCs (professional APCs), macrophages and B
weeks. In chickens, the initial stages of HPAIV infections are cells, being the DCs the most efficient APCs (Abbas et al., 2012d;
usually accompanied by marked depression with ruffled feathers, Kaspers and Kaiser, 2014). Antigen presentation is very similar
loss of appetite, excessive thirst, watery bright green diarrhoea, between mammals and birds. IAV antigens may be processed and
and markedly lower egg production. Adult chickens frequently expressed by APC in two different ways depending on the nature
have swollen combs, wattles, and oedema surrounding the eyes. of the antigen. Influenza A viruses infecting cells (epithelial cells,
Cyanosis is often observed at the tips of the combs and it is not macrophages or DCs) replicate inside the cell and synthesize
uncommon to observe plasma or blood vesicles on the surface viral proteins (Krug et al., 1989; Vervelde et al., 2013). Some of
with dark areas of haemorrhage and necrotic foci. Laid eggs are these proteins are detected by the host cell and degraded by the
frequently without shells. Oedema of the head and the neck are proteasome, which degrades both cellular and viral proteins into
usually observed. The conjunctivae are congested and swollen small peptides that are transported into the endoplasmic reticu-
with occasional haemorrhage. Areas of diffuse haemorrhage may lum (ER) where coupling with MHC I molecule occurs. The
be observed on the legs, between the hocks and feet. Respiratory MHC–protein complexes are then transported through the Golgi
syndrome and mucus accumulation can be significant character- to the plasma membrane of the cell. Once expressed on the cell
istics of the disease. Some severely affected hens may occasionally surface, these complexes are recognized by CD8+ T-cells through
recover, although neurological sequelae may be observed, such interaction with the T-cell receptor (TCR) and co-stimulatory
as torticollis and ataxia. The disease in turkeys, ducks, geese, and molecules (CD28–B7 interaction) (Morrison et al., 1986, 1988;
quail is similar to that seen in chickens, but it may last 2 to 3 days and reviewed in Yewdell and Hackett, 1989; Abbas et al., 2012d;
longer and is occasionally accompanied by swollen sinuses. Mor- Kaspers and Kaiser, 2014). Phagocytosed or endocytosed viral
tality rates may be lower in ducks and geese than those observed particles or debris from apoptotic infected cells that contain viral
for chickens or turkeys, although younger birds may exhibit neu- proteins (i.e. HA, NA and NP) are processed in phagolysosomes.
rological sequelae (Swayne and Halvorson, 2013). Meanwhile, MHC II molecules are transported out of the ER by
HPAI lesions vary depending on the virus tissue tropism, vesicle trafficking through the Golgi. Vesicles carrying MHC II
which may be epitheliotropic, endotheliotropic, neurotropic fuse with the lysosome carrying viral antigenic peptides to assem-
or pantropic (Pantin-Jackwood and Swayne, 2009). Most com- ble the MHC–peptide complexes, which are then transported
monly, histological lesions consist of multi-organ necrosis and/or onto the plasma membrane for antigen presentation to naïve
inflammation and the most consistently affected tissues are brain, CD4+ T-cells (Morrison et al., 1988; and reviewed in Yewdell and
heart, lung, pancreas, and primary and secondary lymphoid Hackett, 1989; Abbas et al., 2012d; Kaspers and Kaiser, 2014).
organs. Lymphocytic meningoencephalitis with oedema, haem- Infection with IAV stimulates the development of T 1
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orrhages, focal gliosis, neuronal necrosis, and neuronophagia are responses driven by CMI and AMI. In addition to secretion of
associated with infection of the vascular endothelium followed IL-12 from the APC and INFγ from NK cells, antigen presenta-
by dissemination of the virus into the neuroparenchyma (Kob- tion through MHC II leads to activation of CD4+ T-cells, also
ayashi et al., 1996b; Mundt et al., 2009; Swayne et al., 2013). Focal known as T helper (T ) cells. These stimuli induce differentiation
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degeneration to multifocal-diffuse coagulative necrosis of cardiac of CD4+ T cell into a T 1 cell and to secrete IFNγ. The CMI
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myocytes has been reported, especially in turkeys, often accom- response to IAVs is characterized by activation of CD8+ cytotoxic
panied by high amount of virus nucleoprotein within the nucleus T lymphocytes (CTL) (Morrison et al., 1986, 1988; Askonas et
and sarcoplasm of degenerating cardiac myofibers. Common al., 1988). Activated T 1 CD4+ T-cells secrete cytokines such
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lesions associated with HPAI virus replication include multifocal as IL-2 and IFNγ, which stimulates clonal expansion of antigen-
coagulative to fibrinoid necrosis of skeletal myofibres, kidneys specific T-cells and activation of macrophages and NK cells to
tubules, hepatocytes, corticotropic cells of adrenal gland, and enhance pathogen destruction, respectively. Activated CD4+ T 1
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pancreatic acinar cells and ducts. The severity of the lymphohisti- cells may also enhance antigen presentation by APCs or activate
ocytic inflammation increases with prolonged survival. Fibrinoid CD8+ to differentiate into effector CTLs by cytokine secretion
necrosis of the vascular wall components or endothelium causes (reviewed in Abbas et al., 2012c). Cytotoxic CD8+ T-cells are
vascular leakage which can vary from oedema to haemorrhages. generally activated directly by antigen presentation through
Lymphoid necrosis, apoptosis, and depletion accompanied or MHC I from infected APCs or epithelial cells, which in conse-
not by fibrinoheterophilic inflammation are common in cloacal quence allows their differentiation into effector CTLs. Effector
bursa, thymus, and spleen. Lesions in the respiratory tract vary CTLs produce perforin and granzymes thus allowing cell death
extensively from minimal to severe. by apoptosis. Activation of CTLs also leads to clonal expansion of
antigen-specific CTLs (reviewed in Abbas et al., 2012c). Effector
CTLs contribute to the containment of the infection, dissemina-
Adaptive immune responses tion, and clearance of IAVs (Askonas et al., 1988; Bender et al.,
Adaptive immune responses to IAVs involve both cell-mediated 1992; Topham and Doherty, 1998).
immunity (CMI) and humoral (antibody)-mediated immunity Antibody production can be stimulated by direct IAV recogni-
(AMI) (reviewed in Suarez and Schultz-Cherry, 2000; Braciale tion from the B cell and or T cell stimulation. B cells are able to
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