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but similar plaque sizes than the wild-type parent strain (Veits et encodes for glycoprotein M (gM), which in ILTV is not glyco-
al., 2003b). This, together with the late transcription of this gene, sylated (Fuchs and Mettenleiter, 1999). Two forms of the UL10
suggests that UL0 is possibly involved in virion morphogenesis, gene product (36 and 31 kDa, respectively) have been described,
DNA cleavage and encapsidation, or in modulation of host cell and neither was affected by treatment with a combination of
gene regulation (Ziemann et al., 1998b; Veits et al., 2003b). In any neuraminidase and/or N-glycosidase, indicating that the trans-
case, the role of UL0 appears to be a minor one during in vitro lated peptide is not modified by glycosylation. A UL10-deletion
ILTV infection, and it has been suggested that this may be due mutant showed deficient growth and replication characteristics in
to the complementing capacity of the UL[–1] gene when the vitro (Fuchs and Mettenleiter, 1999), but in vivo inoculation stud-
UL0 gene is absent, given the high level of amino acid identity ies have not yet been conducted to determine whether this also
between both proteins and their co-localization in the host cell occurs in the natural host. Glycoprotein M forms heterodimers
nucleus (Veits et al., 2003b). The UL0 gene appeared to be a viru- with glycoprotein N (gN), encoded by the UL49.5 ORF in ITLV,
lence factor in vivo, as chickens infected with the UL0 deletion where gM appears to catalyse post-translational modifications in
mutant showed less severe clinical signs and shed significantly gN to produce the mature form of the protein. Complex forma-
less virus than those infected with wild-type parent or rescuant tion and processing of gN appear not to be affected by the absence
viruses, but nevertheless remained protected against subsequent of glycosylation in gM (Fuchs and Mettenleiter, 2005). Neither
virulent ILTV challenge (Veits et al., 2003b). More recent work of these genes is essential for viral replication in vitro (Fuchs and
aimed at isolating a UL[–1] deletion mutant demonstrated that Mettenleiter, 1999, 2005).
this gene, in contrast to UL0, is essential for virus replication, and The conserved peptide encoded by UL11 is involved in
viral propagation could only occur through the complementing secondary envelopment of viral progeny during lytic infection.
capacity of the wild-type genotype (Nadimpalli et al., 2017). The Sequence analysis revealed that, as in other alphaherpesviruses,
dispensable nature of UL0 contrasts with the essential nature of it contains sites for myristoylations and palmitoylation at the
UL[–1] during in vitro infection, which indicates that the protein N-terminus, and also putative casein kinase II and protein kinase
encoded by the UL0 gene does not complement the function of C phosphorylation sites. Transcription analysis determined that
the UL[–1] gene as was previously hypothesized. Both peptides UL11 is a late (γ) gene (Fuchs et al., 2012; Mahmoudian et al.,
share approximately 30% amino acid identity, which may help 2012) and the expressed polypeptide is incorporated into the
explain their evolutionary relationship, but does not necessarily tegument of viral particles (Fuchs et al., 2012). A UL11-deletion
support them both having similar functions. mutant was slower to grow and produced smaller-sized plaques
ILTV also encodes sORF4/3 in each of the repeat regions of in cell culture than wild-type ILTV, suggesting that although
the genome. This sORF4/3 gene is a homologue of sORF3 in not essential for replication, pUL11 is relevant for production of
Gallid alphaherpesvirus 2 (Marek’s disease virus, MDV) and Gallid replication-competent virions and for efficient cell-to-cell spread.
alphaherpesvirus 3 (herpesvirus of turkeys, HVT). Homologues Further ultrastructural studies using immuno-staining with spe-
of sORF4/3 can also be found in other avian herpesviruses, such cific monoclonal antibody determined that the lack of UL11 had
as PsHV1 (Iltovirus), Anatid alphaherpesvirus 1 (Mardivirus), no impact on nucleocapsid assembly or in primary envelopment
Spheniscid herpesvirus 2 and Falconid herpesvirus 1 (unassigned by but resulted in abnormal accumulation of un-enveloped capsids
ICTV, but unofficially assigned to the genus Mardivirus based on inside the cytoplasm with almost no mature virions being released
nucleotide sequence homology) (Spatz et al., 2014), and there- to the extracellular, indicating an alteration in the secondary
fore appears to be specific to avian herpesviruses. The function of envelopment process. Unusual tegument protein accumulations
the protein encoded by this gene in ILTV and other avian herpes- in the cytoplasm and altered membrane structures in the trans-
viruses remains unknown. Golgi network, where secondary envelopment occurs, were also
Other ILTV proteins with known homologues in HSV have observed in cells infected with the UL11-deletion mutant (Fuchs
also been the subject of molecular characterization regarding et al., 2012). The UL11 product normally interacts with the prod-
transcription, processing and/or function. Specific gene deletion uct encoded by UL16 in other alphaherpesviruses, but UL16 is
has been a common tool to better understand the role of these not conserved in the ILTV genome. Despite this difference, ILTV
viral proteins during ILTV infection. In addition to the deletion UL11 appears to have a conserved function in secondary envelop-
mutants already mentioned, there have been deletion mutants ment, which may occur in association with other yet unidentified
isolated for at least another 10 genes of ILTV (Table 11.1) and viral proteins (Fuchs et al., 2012).
attempts to isolate recombinants lacking genes that are consid- Upstream to the UL21 ORF lays an inverted section of the
ered essential for viral replication in other herpesviruses (i.e. UL region that spans from UL22 to UL44 (Fig. 11.1). A similar
glycoprotein D) have failed (Pavlova et al., 2013), thus confirm- inversion is also found in the genome of PsHV1 (Thureen and
ing their essential role in ILTV infection and replication as well. Keeler, 2006), while the genome of PRV has an inversion that
All the genes between the UL1 and UL21 ORFs have been spans from UL27 to UL44 (Klupp et al., 2004). Most of the genes
investigated for transcription (Fuchs and Mettenleiter, 1996, (and peptides) encoded within this inverted region and upstream
1999; Ziemann et al., 1998a; Fuchs et al., 2012; Mahmoudian et remain uncharacterised with a few exceptions (Table 11.1). These
al., 2012) but their products have not been investigated in detail, include UL23 (thymidine kinase, TK), ORFs UL27 (glycopro-
with the exception of those encoded by UL10 (Fuchs and Metten- tein B, gB), UL31, UL37, UL44 (glycoprotein C, gC), UL46, and
leiter, 1999) and UL11 (Fuchs et al., 2012). The ILTV UL10 gene UL48 – UL50.