Biology Reference
In-Depth Information
limited efficacy and high rates of adverse affects. Investigations of the essential
proteins for HCMV replication may lead to novel antiviral strategies. This chapter
will focus on the immediate early two gene (IE2) of HCMV, which encodes the
essential multifunctional IE protein designated IE86. The IE2 gene is in a region of
the viral DNA referred to as the major immediate early (MIE) gene locus.
Transcription from the MIE gene locus does not require de novo viral protein syn-
thesis, and MIE viral transcripts are detected in the presence of an inhibitor of pro-
tein synthesis. The MIE gene locus consists of an enhancer-containing promoter
upstream of the IE1 (UL123) and IE2 (UL122) genes. The transcriptional binding
sites and functions of the MIE enhancer have been recently reviewed (Stinski 1999;
Meier and Stinski 2006). The functions of the IE1 gene product are reviewed (see
the chapter by G. Maul, this volume). This chapter will review our current under-
standing of the functions of the IE2 gene product.
The MIE enhancer-containing promoter generates a primary transcript that
undergoes differential splicing and polyadenylation to produce multiple mRNA
species (Fig. 1). The IE1 and IE2 mRNAs contain the first three exons in common,
but IE1 contains exon 4, while IE2 contains exon 5 (Fig. 1). Translation initiates in
exon 2; consequently the IE1 and IE2 gene products have the first 85 amino acids
in common (Stenberg et al. 1984). Minor isoforms are produced from the IE1 and
IE2 genes, as diagramed in Fig. 1. There is also a late promoter in exon 5 that is
activated after viral DNA synthesis. Less is known about the functions of the isomers
Molec.
weight
(kDa)
AATAAA
MIE
pro
m
oter
Amino
Acids
mRNA
(kb)
ATG
ATG
TAA
Protein
2.25
579
80-86
IE86
5
ENHTA 1
CRS/INR
23
AATAAA
TAA
1.95
491
68-72
IE72
4
1.70
425
55
IE55
0.65
172
38
IE38
1.40
164
18
IE18
ATG
1.50
337
40
L40
Late 40
promoter
Fig. 1
The mRNAs and viral proteins encoded by the IE1 and IE2 genes of HCMV. Abbreviations:
ENH
enhancer,
TA
TATA box,
crs
cis
repression sequence,
INR
initiator,
MIE
major immediate
early,
ATG
start codon,
TAA
stop codon,
AATAAA
polyadenylation signal,
kb
kilobases,
kDa
kilo-
daltons,
IE
immediate early,
L
late
