Page 12 - Avian Virology: Current Research and Future Trends

Avian Influenza Virus | 5

Table 1.2 Influenza A virus genome segments and encoded proteins
Gene segment Nucleotides Proteins (no. of aa*)
1 – Polymerase basic 2 (PB2) 2341 PB2 (759)
PB2-S1
2 – Polymerase basic 1 (PB1) 2341 PB1 (757)
N40
PB1-F2 (87–90)
3 – Polymerase acid (PA) 2233 PA (716)
PA-X (252)
PA-N155
PA-N182
4 – Haemagglutinin (HA) ~ 1700 HA (~ 550)
5 – Nucleoprotein (NP) 1565 NP (498)
6 – Neuraminidase (NA) ~ 1400 NA (~ 450)
7 – Matrix (M) 1023 M1 (252)
M2 (97)
M42
8 – Non-structural (NS) 890 NS1 (230)
NS2/NEP (121)

*Only viral proteins that are consistently expressed in all avian viral strains are shown with amino acid number.

nucleotides at the 3′ and 5′ ends, respectively, that are highly translation initiation sites, and frameshifting (Table 1.2). In
conserved among all IAVs. The vRNAs are present as viral ribo- addition, each of these protein products may carry pleotropic
nucleoprotein (vRNP) particles (Fig. 1.1). Through base pairing functions that ultimately favours virus replication and counter-
due to partial inverted complementarity, these termini push acts the host’s antiviral responses.
each of the vRNA segments to form a panhandle and adopt a
‘corkscrew’ double-stranded structure that serves as promoter Viral genes and proteins, viral protein functions
for viral transcription and replication (Hsu et al., 1987; Parvin et
al., 1989; Azzeh et al., 2001; Brownlee and Sharps, 2002; Crow Segment 1: PB2 and PB2-S1
et al., 2004; Tomescu et al., 2014). The double stranded termini Segment 1 encodes the polymerase subunit PB2, which rec-
region is also associated to the heterotrimeric polymerase com- ognizes and binds the 5′ end methylated cap (5′ 7-methyl
plex consisting of the polymerase basic subunits 1 (PB1) and 2 guanosine triphosphate) of host nuclear pre-mRNAs through
(PB2) and polymerase acidic subunit (PA) (Flick and Hobom, a region spanning amino acids 318 to 483 (Plotch and Krug,
1999). Eight of each of the polymerase subunits are package per 1977; Plotch et al., 1981; Braam et al., 1983; Perales et al.,
virion (Fig. 1.1). In addition, the vRNAs are wrapped around 1996; Perales and Ortín, 1997). PB2 is required for viral
the nucleocapsid (NP) protein at a ratio of approximately one transcription and replication and interacts directly with PB1
copy of NP every 24 nucleotides of RNA. The vRNPs constitute and NP on overlapping regions mapped within the N-terminal
the essential units of influenza virus transcription and replica- ~ 250 amino acids and the C-terminal ~ 180 amino acids
tion (Huang et al., 1990). The panhandle termini are part of (González et al., 1996; Poole et al., 2004). In PB2, the region
the untranslated regions (UTRs) at the 5′ and 3′ ends whose from amino acid 1 through 35 interacts specifically with PB1.
length and sequence varies depending on the gene segment The PB1 binding site overlaps also with the binding site to the
(Tchatalbachev et al., 2001; Hutchinson et al., 2010). The UTRs mitochondrial antiviral signalling protein (MAVS), but such
along with 5′ and 3′ sequences spanning portions of the open interaction is likely an attribute found in mammalian-adapted
reading frame (ORF) form the packaging signals of each seg- strains and not of avian-origin IAVs (Carr et al., 2006). PB2
ment. Several studies suggest the existence of both a hierarchy contains a bipartite nuclear targeting sequence (NLS) span-
and segment–segment interactions that likely contribute to the ning amino acids 736–739 (NLS-1) and 752–755 (NLS-2)
packaging of eight vRNA segments inside the virion in a ‘7+1’ that allows the protein to transit to the nucleus via the host’s
configuration (a central vRNP surrounded by seven additional importin pathway (Resa-Infante et al., 2008). PB2 interacts
vRNPs) (Fujii et al., 2005; Marsh et al., 2007, 2008; Hutchinson with retinoic acid-inducible gene I (RIG-I) (Li et al., 2014a).
et al., 2009; Ozawa et al., 2009; Noda and Kawaoka, 2010, 2012; In fact, PB2, PB1, and PA can bind RIG-I from various hosts
Wise et al., 2011; Chou et al., 2012; Gao et al., 2012, 2013; (human, swine, mouse, and duck) in a RNA-independent
Brooke et al., 2014; Nakatsu et al., 2016; Noda et al., 2018). manner, either each subunit independently or as complex,
Despite their small genome, influenza viruses pack multiple but the binding of NP with RIG-I is RNA dependent (Li et
gene products that are produced from a variety of mechanisms al., 2014a). However, the exact biological significance of the
that include translation of colinear or spliced mRNAs, alternative RNP–RIG-I interactions in the replication and pathogenicity