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Avian Immune Responses to Virus Infection | 387

sequences elicited protection from challenge (Hou et al., 2012; class I molecules from the cell surface. There have been reports
Tan et al., 2016). In another approach, overlapping peptides from of class I down-regulation upon reactivation of virus in MDV
AIV identified a peptide that elicited cytokine secretion from transformed cells (Hunt et al., 2001), with one study implicating
and proliferation of both CD4 and CD8 cells from B19 chickens the UL49.5 gene (Jarosinski et al., 2010) and another implicating
(Haghighi et al., 2009). Finally, a powerful approach used often the MDV012 gene (Hearn et al., 2015). In chickens, both TAP
for mammals is the production of a soluble MHC molecule and tapasin are polymorphic (Walker et al., 2011; van Hateren et
bound to a particular peptide, the complex of which can be mul- al, 2013), which in principle might be a counterstrategy to viral
timerized to increase binding to specific T-cells (often referred immune evasion proteins.
to as MHC-peptide tetramers when streptavidin is used to mul- A more subtle method of evasion is to stimulate inappropriate
timerise) detected by flow cytometry (Xu and Screaton, 2002). or regulatory (suppressive) CD4 T-cell responses. Such a misdi-
Thus far, this approach has only been reported for an IBV peptide rection of the immune response has been proposed for the MDV,
d
(identified by I-E class II molecule reactive mouse T-cells) with which was reported not to stimulate a Th1 CD4 response appro-
BF2*15:01 and NDV in chickens (Liu et al., 2013). priate for inflammation and viral infection during the cytolytic
By contrast, far less is understood about peptides and presen- (acute) phase of MDV infection, but rather a Th2 CD4 response
tation by chicken class II molecules to CD4 cells, an interaction more appropriate for multicellular parasites and wound healing
which is important for initiating most CD8 T-cell responses (Heidari et al., 2008).
as well as helping the B cell responses to produce appropriate
antibodies. Self-peptides eluted from B19 and B21 cells have Vaccines
been reported for chicken class II molecules (Haeri et al., 2005; Vaccination is one of the great success stories of both human
Cumberbatch et al., 2006). Functional assays for specific anti- and farm animal medicine and is a consequence of the adaptive
gen presentation by class II molecules on APCs to T-cells from immune response. The initial (or primary) response to immuniza-
chickens immunized with keyhole limpet hemocyanin have been tion is relatively slow, but subsequent encounters are much faster
reported (Vainio et al., 1988), but CD4 responses to viruses are and more specialized. The slow primary response is due, at least
limited to AIV-infected macrophage presentation (to both CD4 in part, to the enormous variety of clonal receptors, both TCRs
and CD8 cells) as assessed by IFNγ secretion, for which the B2 and BCRs, so that there are relatively few naïve lymphocytes with
haplotype was greater than B19 (Collisson et al., 2017). any one receptor. Upon immunization with an antigen, these few
naïve lymphocytes proliferate over days resulting in many acti-
Evasion of the adaptive immune response by vated cells, which are selected for appropriate effector responses.
viruses Some of these activated cells become so-called memory cells,
Viruses can evade the MHC-dependent immune response in which are larger in number and more easily activated than the
several ways. In the infection of an individual host, viruses with a naïve cells were, and thus respond more quickly and aggressively
reasonable mutation rate will result in a swarm (or quasi-species) upon re-encounter with antigen.
of closely related viruses. CTLs will not recognize and kill cells Vaccination is widely used, along with biosecurity and genetic
infected by viruses that have changed residue(s) necessary for pep- resistance, for protection of poultry against viral pathogens.
tide binding to the classical class I molecule(s) in that individual, The practical aspects of poultry vaccination have been reviewed
so that such mutated viruses will be selected. Promiscuous class (Schijns et al., 2013). Attenuated live viral vaccines are commonly
I molecules might be harder to evade in this way, since mutated employed for poultry, due to the ease of attenuating viruses by
peptides may still bind, perhaps explaining why the B2 and B21 repeated passage in eggs or in cultured cells which have no strong
haplotypes confer resistance to many different viruses (Kaufman, selection for the virus to maintain immune evasion mechanisms,
2018). However, fastidious molecules may also confer resistance and to the relatively low cost of producing and spreading live
to certain viruses; for example, HLA-B*057:01, B*027:05 and viruses. Such viral vaccines are weakened compared with the
B*058:01 each bind a particular peptide that the human immuno- original virulent virus, and so can elicit an immune response
deficiency virus (HIV) can change to evade the immune response without overt disease. They also can elicit both cellular (T-cell)
but only with enormous loss of fitness (Schneidewind et al., 2007; and humoral (B cell and antibody) responses through a Th1
Miura et al., 2009). Similarly, antibody responses may be evaded response. Attenuated live vaccines are relatively easy to deliver in
by mutating peptides that would bind to the class II molecules. water or spray and are widely used in the field to protect against
Thus far, there have been no tests of these possibilities for chicken many pathogenic poultry viruses, including AIV, IBDV, IBV, ILT,
MHC molecules. MDV and NDV.
Viruses also evade the response more generally by interfer- Viral-vectored vaccines use a live attenuated virus to express an
ing with antigen processing and peptide loading. Many viruses antigen from another virus (that is, a so-called subunit vaccine),
that infect mammalian cells use a wide variety of mechanisms and therefore come with many of the same advantages. Fowlpox
to down-regulate peptide presentation by class I molecules to virus (FPV) has been used for a variety of experimental vaccines
T-cells (Früh et al., 1999; Griffin et al., 2010; Verweij et al., 2015). as well as some commercial vaccines, particularly against AIV and
For instance, herpesviruses express proteins that block TAP NDV. More recently, herpesvirus of turkeys (HVT) that could
translocation of peptides, degrade class I molecules, retain class protect against early strains of MDV has been adapted to express
I molecules in the Golgi apparatus, and enhance endocytosis of antigens from other viruses and used in the field for IBDV. In