Page 26 - Avian Virology: Current Research and Future Trends

Avian Influenza Virus | 19

PA, are able to interact with interferon β promoter stimulator 1 with most intra-subtype diversity emerging within the last 100
(IPS-1), also known as mitochondrial antiviral protein (MAVS), years, indicating constant selection pressure in the natural reser-
inhibiting activation of IFNβ promoter and limiting production voir (Chen and Holmes, 2006).
of IFNβ (Graef et al., 2010; Iwai et al., 2010). PB1-F2, also has Small amino acid changes that occur on the viral surface
type I IFN antagonistic effect and some proteins (with serine at proteins, particularly the HA, can alter its antigenic features in
position 66) can interact with IPS-1 or MAVS (Conenello et al., such a way that prior antibody responses against the virus cannot
2011; Dudek et al., 2011; Varga et al., 2011). longer neutralize it. Such phenomenon is known as ‘antigenic
Immune evasion by IAVs is also associated to direct or indi- drift’ and occurs during replication while the virus tries to evade
rect impact on cells driving the immune response. IAVs were immune responses. Antigenic drift is also observed on the NA,
able to infect monocytes and impair their differentiation into but its mutation rate is slower than the one observed for the HA,
DCs (Boliar and Chambers, 2010). Furthermore, it has been most likely because antibody responses against the NA are not
discovered that the NS1 protein is capable of decreasing human as potent to stop virus infection and spread. The gene segments
DC maturation and expression of co-stimulatory molecules for encoding the internal viral proteins are more conserved, but small
antigen presentation to T-cells (Fernandez-Sesma et al., 2006). amino acid changes can also occur that may impact the virus’ abil-
On the other hand, it is also known that PB1-F2 targets the mito- ity to expand or restrict replication in other species.
chondrial inner membrane and induces the intrinsic pathway of Owing to the segmented nature of their genomes IAVs can
apoptosis of infected epithelial and immune cells (Chen et al., exchange gene segments, a process also known as reassortment,
2001; Gibbs et al., 2003a; Zamarin et al., 2005; Chakrabarti and which represents one of the major evolutionary forces that pro-
Pasricha, 2013). There is evidence that suggests that glycosyla- mote natural IAV diversity. Reassortment occurs when two or
tion patterns on the HA of H3N2 viruses may impact recognition more different strains of different subtypes infect the same cell
of infected cells by NK cells and reduce NK-mediated cell lysis at the same time, which ultimately allows for the selection of a
(Owen et al., 2007). Additionally, IAVs are able to infect NK cells progeny virus better fit than the parental strains. Reassortment
causing apoptosis, and can also be involved on down-regulation can involve any gene segment. In fact, in the natural reservoir
of the zeta chain of the NK receptor, impairing degranulation in there appears to be no restrictions of the gene segments that can
vitro (Mao et al., 2009, 2010). be exchanged. Natural infections with one or more IAV strains of
Influenza A viruses can also evade the antibody-mediated different subtypes are commonly observed in samples obtained
immune response. The main mechanisms of immune evasion from ducks and other waterfowl. The advent of next generation
conferred by the HA include antigenic drift and antigenic shift. sequencing directly from swab material has led to the realization
Antigenic drift consists of point mutations generated during rep- that co-infections are perhaps more common than previously
lication due to a lack of proof-reading from the RNA polymerase. observed. ‘Antigenic shift’ occurs when reassortment leads to the
Antigenic shift is a result of the IAV segmented genome. As a con- emergence and spread of an IAV strain with a novel HA subtype
sequence, co-infection of a host with more than one IAV virus can in a naïve population. Antigenic shift played a major role in at
lead to gene segment swapping (reassortment), in which segments least two of the three influenza pandemics of the 20th century.
from one virus are packaged with segments from a different virus Thus, a novel H2N2 virus emerged in the human population in
into a single virion. Both mechanisms lead to antigenic differences 1957, known as ‘Asian flu pandemic’, that replaced the previously
that alter recognition of the new IAV variant by CTLs and anti- circulating H1N1 virus. Then again, in 1968 a novel H3N2 strain
bodies, leading to outbreaks and pandemics (reviewed in de Jong produced the ‘Hong Kong pandemic flu’ and, ultimately, replaced
et al., 2000; van de Sandt et al., 2012). In addition, glycosylations the previously circulating H2N2 virus. Full details of the circum-
on the surface of IAV also play an important role on evasion of the stances and mechanisms leading to pandemic influenza strains is
immune response, limiting accessibility to the HA antigenic sites, beyond the scope of this chapter, but it is important to note that
affecting recognition by antibodies and other immune effectors pandemic influenza strains have always carried gene segments
(Das et al., 2011; Tate et al., 2014; Wu and Wilson, 2017). As new derived from IAVs in the avian reservoir.
information arises, our understanding of the biology of IAVs and The evolution of IAVs is best tracked by sequencing the viral
their interaction with the host cell gets expanded. However, there genome (or portions of it) and comparing groups of strains in
are many mechanisms yet to be unveiled. a phylogenetic tree. Sequencing is also used to track mutations
linked to IAVs’ antiviral resistance. Phylogenetic analyses allow
the separation of IAVs into lineages depending on the animal
Virus evolution and reverse genetics species of origin (avian versus mammalian, horse versus human
Influenza viruses constantly evolve due to the lack of proof- versus pig, etc.) and geographical distribution. With respect to
reading activity of the viral polymerase and the tolerance of the IAVs circulating in waterfowl, two major lineages have been
viral proteins to accept changes. During replication, the virus may observed and are classified as Eurasian and North American
introduce mutations that are either synonymous (no change in lineages. More recently, a third South American lineage was
the encoded amino acid) or non-synonymous (change of the described, which is in itself the result of a complex evolutionary
−4
−3
encoded amino acid), with a rate of 10 to 10 per replication history involving ancestors of the Eurasian and North American
cycle. It has been estimated that the common ancestors of the HA lineages (Pereda et al., 2008; Alvarez et al., 2010; Rimondi et
and NA subtype sequences emerged within the last 3000 years, al., 2011; Xu et al., 2012; Nelson et al., 2016). Evidence exist