Page 25 - Avian Virology: Current Research and Future Trends

18 | Perez et al.

recognize pathogens through the B cell receptor (BCR). Antigen which has been explored as a strategy for broadly protective vac-
recognition through the BCR complex leads to receptor-mediated cine development (Wu et al., 2009; Park et al., 2011; Chowdhury
endocytosis and antigen processing. The processed IAV antigenic et al., 2014; Kolpe et al., 2017). Recent studies with human
peptides are then expressed on the surface, coupled with MHC sera and transgenic mice showed some protection conferred by
II and presented to a CD4+ T 1. Antigen presentation through NP-specific antibodies, suggesting their involvement on ADCC
H
this interaction leads to production of IFNγ and other cytokines, (Carragher et al., 2008; Fujimoto et al., 2016; Jegaskanda et al.,
which, in turn, induce isotype switching (from IgM to IgY in 2017).
birds or IgG in mammals), affinity maturation, B cell differentia-
tion into IAV antibody-secreting plasma cells, and generation of
memory B cells (Virelizier et al., 1974a,b; Lucas et al., 1978; and Immune evasion strategies of influenza A
reviewed in Yewdell and Hackett, 1989; Abbas et al., 2012a,d). viruses
The main roles of antibodies directed to IAV are to neutralize Influenza A viruses evade the host’s immune responses through
the virus and limit its spread by decreasing release of new virions different mechanisms. IAV evades the innate immune response
and enhance pathogen elimination by macrophages and NK cells by disrupting IFN signalling and antiviral gene expression in
through different mechanisms. Binding of IgY/IgG antibod- multiple ways. The NS1 protein from some IAV has the ability
ies to IAV particles and to its antigens expressed on the surface to block the Jak/STAT signalling pathway and inhibit activation
of infected cells, enhance pathogen/antigen recognition and of IRF3 and NF-κB by up-regulation of suppressor of cytokine
destruction by macrophages and NK cells. Antibody-dependent signalling 1 (SOCS1) and SOCS2, which also inhibits TLR sig-
phagocytosis (ADP) is one of the effector mechanisms triggered nalling (García-Sastre et al., 1998; Gingras et al., 2004; Mansell et
by antigen–antibody (Ag–Ab) complexes. The Fc receptor on the al., 2006; Pauli et al., 2008; Pothlichet et al., 2008; Jia et al., 2010).
macrophage surface interacts with the Fc region on the antibody Down-regulation of chicken IFN expression by SOCS1 has also
of the Ag–Ab complex enhancing phagocytosis, which, in turn, been shown in vitro (Giotis et al., 2017). Another mechanism by
leads to pathogen destruction and continuing antigen presenta- which NS1 can inhibit IFN production is by binding the 30kDa
tion (Dorrington, 1976; Huber et al., 2001; Swanson and Hoppe, subunit of the cellular cleavage and polyadenylation specificity
2004; Guilliams et al., 2014; Ana-Sosa-Batiz et al., 2016). A factor (CPSF30) that is required for the 3′ end processing of cel-
second mechanism triggered by the Ag–Ab complexes is known lular pre-mRNAs (Nemeroff et al., 1998; Noah et al., 2003; Kochs
as antibody-dependent cell-mediated cytotoxicity (ADCC). In et al., 2007; Das et al., 2008). Moreover, NS1 from some IAVs
this case, the Ag–Ab complexes are constituted by antibodies can prevent TRIM25-mediated ubiquitination of RIG-I CARD
bound to antigens presented on an MHC I on infected cells and domain, preventing downstream signalling and expression of
is mediated by NK cells. The Fc antibody region is bound by the type I IFN (Gack et al., 2009). It has been proposed that activa-
Fc receptor on the NK cell, which triggers the destruction of the tion of IRF3 and NF-κB can also be inhibited by binding viral
infected cell by release of perforin and granzymes from the NK dsRNA during replication (Talon et al., 2000; Wang et al., 2000).
cell (Hashimoto et al., 1983; Okabe et al., 1983; Abbas et al., In addition, there is evidence that NS1 is capable of binding to
2012b) aiding in the elimination of infected reservoirs. dsDNA, inhibiting RNA Polymerase II recruitment to the exon
Antibodies directed to the HA and NA have been shown to and promoter regions of IFNβ1 in vitro (Anastasina et al., 2016).
be the main players on the induction of protective immunity. In recent years, the capability of NS1 to bind to human PAF1 tran-
Antibodies against the HA are able to neutralize the virus by scriptional elongation complex (hPAF1C) was presented. This
preventing receptor binding and receptor mediated endocytosis, interaction is based on a histone mimic sequence present at the
or by preventing HA pH-dependent conformational changes NS1 C-terminus and leads to suppression of hPAF1C-mediated
and therefore, virus-endosomal membrane fusion (Wiley et al., transcriptional elongation, resulting in antiviral gene expression
1981; Barbey-Martin et al., 2002; Sui et al., 2009; Kaminski and (Marazzi et al., 2012). NS1 is also capable of inhibiting activation
Lee, 2011; Xiong et al., 2015; Kallewaard et al., 2016). Antibod- of protein kinase R (PKR) and oligoadenylate synthase (OAS)
ies directed to the NA are not considered neutralizing; however, (both type I IFN-induced proteins and activated by dsRNA),
they have the capability to block NA neuraminidase activity, which are responsible for the activation of eIF2 translation ini-
preventing successful release of newly generated virions and thus tiation factor and ribonuclease L (RNase L), respectively. NS1
contributing to decreased viral spread (Kilbourne et al., 1968; prevents activation of PKR by direct binding, preventing phos-
Schulman et al., 1968; Johansson et al., 1989; Han and Marasco, phorylation and activation of eIF2 translation initiation factor,
2011; Kaminski and Lee, 2011; Liu et al., 2015b). Studies in blocking its ability to inhibit viral replication (Li et al., 2006; Min
different animal and in vitro models, have shown that HA- and et al., 2007). As for inhibition of OAS activation, it is believed that
NA-specific antibodies are capable of inducing ADCC driven NS1 binding to dsRNA blocks the interaction between dsRNA
by NK cells (Justewicz et al., 1984; Jegaskanda et al., 2013; Ye et and OAS, inhibiting its activation and downstream activation of
al., 2017). Antibodies against other proteins such as NP and M2 RNase L, thus preventing cleavage of viral ssRNA and inhibiting
play a smaller role on immunity against IAV. There is some evi- viral replication (Min and Krug, 2006; and reviewed in Silver-
dence suggesting that antibodies reacting against the N-terminus man, 2007; Krug, 2015).
of M2 could inhibit viral replication of IAV in vitro and in mice, Other viral proteins have been found related to immune eva-
after infection with different IAV subtypes (Wang et al., 2008), sion. Some variants of PB2, alone or in association with PB1 and