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350 | Lupiani et al.

In HSV-1, a null mutation of the UL12 gene did not affect DNA Ribonucleotide reductase (RR, MDV052/UL39 and
replication and late proteins expression; however, virion produc- MDV053/UL40)
tion was affected, especially the formation of DNA-containing MDV ribonucleotide reductase is encoded by MDV052 and
capsids, indicating that alkaline nuclease is involved in the pro- MDV053, homologous genes of HSV-1 UL39 and UL40. RR
cessing or packaging of viral DNA into infectious virions (Shao plays a role in the generation of deoxyribonucleotides from
et al., 1993). ribonucleotides (Reichard, 1988). RR consists of two subu-
nits, RR1 and RR2, with molecular sizes of 90 kDa and 40 kDa,
Uracil DNA glycosylase (UDG, MDV014/UL2) respectively. Deletion of RR1 in a very virulent plus MDV-1 virus
MDV uracil DNA glycosylase is encoded by MDV014, a homo- demonstrated that RR activity is important but not essential for
logue of HSV-1 UL2. UDG is an enzyme that catalyses the replication in chicken embryo fibroblasts (CEF). On the other
cleavage of the N-glycosidic bond linking uracil to deoxyribose, hand, in vivo studies, showed that the RR1 deletion mutant virus
and then the DNA is repaired by AP endonuclease, DNA poly- was impaired for its ability to replicate in chickens (Goldstein and
merase, and DNA ligase (Friedberg et al., 2005). UDG of HSV-1 Weller, 1988; Lee et al., 2013).
plays a role during acute viral replication and during reactivation
from latency (Pyles and Thompson, 1994). UDG interaction MDV unique regulatory proteins and RNAs
with Pol might play a critical role for base excision repair during Apart from structural and replication proteins, the MDV genome
DNA replication (Bogani et al., 2010). encodes several proteins and RNAs, such as Meq, vTR and MDV-
encoded miRAs (Fig. 12.2), which regulate cellular pathways and
Deoxyuridine triphosphatase (dUTPase, MDV063/ in turn, benefit the survival of the virus.
UL50)
MDV deoxyuridine triphosphatase is encoded by MDV063, a Meq
homologue of HSV-1 UL50. The dUTPase catalyses specific The gene meq or MDV005/MDV076, is located in the TRL and
hydrolysis of dUTP to dUMP and inorganic pyrophosphate. IRL regions and codes for Meq (MDV Eco Q fragment), a 339
In HSV-1, dUTPase is not required for viral growth in cell amino acid long b-ZIP protein which consists of a N-terminal
culture, but does play a role in the infection cycle, and it affects DNA-binding domain, a leucine zipper domain, and a C-terminal
neurovirulence, neuroinvasiveness, and reactivation (Pyles et transactivation domain (Fig. 12.3) (Lupiani et al., 2004). Meq
al., 1992). is expressed during the lytic phase as well as in lymphoblastoid
tumour cells and has homology to members of the Jun-Fos leu-
Thymidine kinase (TK, MDV036/UL23) cine zipper family (Jones et al., 1992). Meq is a multifunctional
MDV thymidine kinase is encoded by MDV036, a homologue of protein which has been shown to be involved in transactivation/
HSV-1 UL23, is highly conserved among alphaherpesviruses and transrepression, DNA binding, chromatin structure remodelling
gammaherpesviruses. The major function of TK is to phosphoryl- and transcriptional regulation (Osterrieder et al., 2006). Deletion
ate thymidine and other nucleosides. In HSV-1, it has been shown of both copies of the meq gene showed that Meq is essential for
that deletion of UL23 does not affect virus latency but affects the transformation of lymphocytes but not required for cytolytic
virus reactivation (Coen et al., 1989). infection in the feather follicular epithelium (FFE) and lymphoid

TRL IRL IRS TRS
UL US

IRL IRS

pp38 Cluster 1 meq Cluster 2 vIL8 vTR Cluster 3 ICP4
miRNAs miRNAs miRNAs

1.8 Kb LAT
transcript
meq/vIL8

Figure 12.2 Schematic representation of MDV genomic structure showing genes in repeat regions.

Figure 2