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Figure 4.4 Three different models of cell to cell spread proposed for HMPV in BEAS-2B cells. In the first model (1) virus particles are
transferred from an infected cell to a new target cell in open-ended intercellular extensions. In the second model (2), the virus particles move
along the surface of intercellular extensions, and in the third model (3) RNPs are transmitted inside intercellular extension. Reprinted with
permission from El Najjar et al. (2016).

for Avian paramyxovirus, has not yet been developed (Liu et al., of HMPV allowed HMPV to grow in an avian cell culture (de
2017). Graaf et al., 2009). A study focusing on a practical use of the
AMPV reverse genetics systems, like those developed for system by producing modified viruses for control purposes in
other negative-sense viruses including RSV and HMPV have molecular diagnostics has also been reported (Falchieri et al.,
and continue to contribute enormously to the understanding of 2012). Of course the main practical use of a system that allows
virus function. Several subgroup-A viruses produced by reverse precise modification of the viral genome is in vaccine develop-
genetics have demonstrated that the M2.2, SH or G genes were ment. In this field the ability to produce recombinant clonal virus
not essential for virus replication in vitro or in vivo however, in stocks with controlled attenuation and stability or that can serve
vivo they were attenuated (Naylor et al., 2004; Ling et al., 2008). as vectors to deliver proteins of other viruses are not negligible.
Deletion of M2.2, SH or G in HMPV have also been shown to However, to date no commercial vaccine is available based on a
be non-essential for virus replication both in vitro and in vivo and live recombinant AMPV. Conversely, RG have allowed the devel-
also to be attenuated in vivo (Buchholz et al., 2005). A subgroup- opment of genetically engineered derivatives of other viruses,
C virus (turkey virus) with a deleted M2.2 was also shown to the most recent of which being a recombinant Newcastle disease
replicate in vitro. However, unlike AMPV-A and HMPV, M2.2 virus (Hu et al., 2017) which express MPV F and G genes and
was shown to be essential for sufficient replication of the virus to could be used as recombinant vaccine against AMPV. Clearly
sustain sufficient immunogenicity in vivo (Yu et al., 2011). The more fundamental studies are required.
most recently developed RG system for a duck subgroup-C will
be helpful in unravelling the molecular basis of the host range of
AMPV-C (Szerman et al., 2018). Pathogenesis
In 2006, it was shown that the RNPs of US AMPV-C
(turkey virus) and HMPV were interchangeable for rescue of Host range
either virus (Govindarajan et al., 2006; de Graaf et al., 2008a) The principal species for AMPV seem to be turkey and chicken
and most recently a similar study showed that the RNPs of sub- for subgroup A and B viruses, turkey and ducks for the subgroup
group A and B were also interchangeable (Laconi et al., 2016) C viruses and turkeys for the subgroup D viruses. However,
for rescue of either virus. These RNP swapping studies need to pheasants and guinea fowl are also susceptible (Picault et al.,
be completed with the inclusion of the subgroup D virus and 1987; Gough et al., 1988, 2001; Catelli et al., 2001; Ogawa et al.,
the subgroups C virus of ducks. Swapping of the RNPs between 2001; Lee et al., 2007). Interestingly, chickens and pheasants are
the ‘Type I’ (AMPV-A, B or D) and ‘Type II MPVs’ (AMPV-C two species from which both subgroup A and C viruses have been
and HMPV) would provide invaluable information regarding isolated and thus may represent important species in terms of
conserved functional RNP motifs for the genre metapneumo- AMPV evolution. Considering isolation, AMPV-A and B viruses
virus. have been isolated from both turkeys and chickens in numerous
Other studies using reverse genetics of AMPV include the studies (Collins et al., 1986; McDougall and Cook, 1986; Wilding
identification of two zones of amino acid sequences within the F et al., 1986; Wyeth et al., 1986; Picault et al., 1987; Cook et al.,
protein ectodomain of a subgroup A virus that were recognized 1993a) AMPV-D from turkeys (Bayon-Auboyer et al., 2000) and
by neutralizing antibodies (Brown et al., 2009) and another in AMPV-C viruses from turkeys, chickens, ducks and pheasants
which the F protein of an AMPV C incorporated into the genome (Cook et al., 1999; Toquin et al., 1999a; Bennett et al., 2004; Lee