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encode 8 main proteins (nucleoprotein [N], phosphoprotein
[P], Matrix protein [M], Fusion protein [F], M2 protein, small
hydrophobic protein [SH], attachment glycoprotein [G] and
polymerase protein [L]) whilst pneumovirus genomes encode
two extra proteins NS1 and NS2 for a total of 10. The other
main difference is the transposition of SH-G genes closer to the
proximal 5′ and F-M2 genes closer to the proximal 3′ end of the
genome in Metapneumoviruses. It has been suggested that this
reorganization could have arisen from a recombination event
(Easton et al., 2004); a hypothesis indirectly supported in two
recent reports, one implicating recombination in the evolution
of HMPV (Kim et al., 2016) and a second demonstrating cell to
cell transmission of HMPV virus particles and or just the viral
ribonuclear complexes (RNPs) between cells through connected
cellular extensions (El Najjar et al., 2016). This mechanism could
eventually increase the chances of having two different genomes Figure 4.3 Genetic relationships between MPV genome sequences.
present in the same cell at the same time, one passing between The tree was constructed using the neighbour-joining method.
Percentages at branch points represent the number of times the
cells unseen by the immune system and a second ‘classically’ group to the right of that branch point occurred among 1000 trees
infecting the cell. However, to date there has still only been one generated by bootstrap from the original alignment. Re-printed with
report clearly demonstrating the potential for pneumoviruses to permission from Brown et al. (2014).
recombine (Spann et al., 2003); thus, further study is required.
The order in which these genes appear in the genome has also
been shown to have an effect on mRNA transcription, with mRNA the authors note one surprising observation in the length of the
of genes placed closer to the 3′ end of the genome being more leader sequence of AMPV-D which was 7 nt longer than any other
abundant as in other Mononegavirales (Krempl et al., 2002). For MPV. These molecular data were of course based on the limited
this reason, if we accept that increased mRNA generally relates to number of full-length sequences currently available especially in
increased expression of that molecule, one may hypothesize that the case of AMPV-D for which only two such isolates currently
the position of F and G in metapneumovirus genomes means that exist or have been reported worldwide (Bayon-Auboyer et al.,
they require a greater abundance of fusion protein than they do of 2000). Thus, it is possible to envisage further modifications to
the attachment glycoprotein G and vice versa for pneumoviruses. the molecular relationships of MPVs when more full-length
Furthermore, it may explain why deletion of the G gene in MPV’s sequences become available with the ever-increasing access to
is less detrimental to virus replication in vivo (Biacchesi et al., next generation sequencing platforms.
2004b, 2005; Ling et al., 2008) than the same deletion is to RSV
replication in vivo (Teng et al., 2001). Functions of the viral protein
This topic has been extensively reviewed for viruses of the family
Viral nucleic acids and proteins Pneumoviridae (Easton et al., 2004; Schildgen et al., 2011; Brown
Currently, Metapneumovirus genomes are known to transcribe et al., 2014). In brief, the viral N, P and L proteins are the essential
eight mRNAs which are translated into 9 proteins: The nucle- components of the polymerase complex which replicates and
ocapsid (N) protein, the phosphoprotein (P), the matrix (M) transcribes viral genome molecules. Detailed structural studies on
protein, the fusion (F) protein, the M2.1 and M2.2 protein from how these proteins interact have recently been published (Renner
bicistronic M2 mRNA, the small hydrophobic (SH) protein, the et al., 2016, 2017). The polymerase complex has a close interac-
glycoprotein (G) and the large polymerase protein (L). tion with the M2 proteins whose balance has been suggested to
The molecular analysis of full-length virus sequences of modulate the switch between replication and transcription. M2
AMPV subgroups A, B, C and D and HMPV subgroups A and proteins have also been suggested to alter the fidelity of the poly-
B have recently been described in detail (Brown et al., 2014). merase complex (Buchholz et al., 2005; Schildgen et al., 2011).
In summary, this report showed that the longest and the short- The P protein has also most recently been shown to be capable
est genomes belong to the AMPV-C viruses at 14,152 nt and of modifying the form of infected cell membranes creating exten-
13,134 nt, respectively, and that they had a greater sequence sions between cells and is thus also a key protein in assembly and
homology at the nucleic and the amino acid level in all areas of spread (El Najjar et al., 2016).
the genome with HMPV than they did with AMPV-A, B and D. The Matrix protein orchestrates the assembly of the viral com-
AMPV-A, B and D shared a greater sequence homology at the ponents and has been shown to result in conformational changes
nucleic and the amino acid level in all areas of the genome than of the cell membrane when in the presence of the F protein (El
they did with AMPV-C or HMPV. Phylogenetic relationships of Najjar et al., 2016). The F protein is arguably the most important
full length MPV genome sequences are shown in Fig. 4.3. The of the three viral surface proteins (F, SH and G) as unlike the SH
same relationships were observed in non-coding and intergenic and G protein it is indispensable for virus viability. Recombinant
regions as well as in the leader and trailer sequences however MPV’s engineered to express only the F protein as their surface