Virology. 1998 Mar 1;242(1):128-37. Related Articles, Links


The herpes simplex virus immediate-early protein ICP27 shuttles between
nucleus and cytoplasm.

Mears WE, Rice SA.

Department of Biochemistry, university of Alberta, Edmonton, Canada.
steve_rice@darwin.biochem.ualberta.ca

ICP27 is an essential herpes simplex virus type 1 (HSV-1) nuclear
protein which regulates viral early and late genes during infection.
The exact mechanism by which ICP27 modulates viral gene expression is
unknown, but considerable evidence suggests that it functions
posttranscriptionally. In this study, we have asked whether ICP27, like
some other viral and cellular posttranscriptional regulatory proteins,
shuttles between the nuclear and cytoplasmic compartments of the cell.
Using an interspecies heterokaryon assay, we demonstrate that ICP27,
but not the HSV-1 nuclear proteins ICP4 or ICP8, is an efficient
shuttling protein. ICP27's shuttling ability does not depend on viral
infection or other HSV-1 proteins, as it shuttles even when transiently
expressed in uninfected cells. To understand the importance of
shuttling for ICP27's regulatory functions, we examined several mutant
forms of ICP27 to see whether they exhibited altered shuttling. We
identified three ICP27 mutations which partially disrupt shuttling, as
well as one mutation, M15, which completely abrogates this activity.
The M15 mutation alters residues 465 and 466 near the carboxyl terminus
of ICP27 and was previously shown to inactivate ICP27's ability to
induce certain viral late mRNAs. These results suggest that ICP27's
nuclear shuttling activity is involved in its viral late gene
activation function.

PMID: 9501050 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/..0&dopt=Abstract

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full article:
http://jvi.asm.org/cgi/reprint/71/1..nt&pmid=9371577

Shuttling of the Herpes Simplex Virus Type 1 Regulatory
Protein ICP27 between the Nucleus and Cytoplasm Mediates
the Expression of Late Proteins

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http://jvi.asm.org/cgi/content/full..g&pmid=15767413

Control of VP16 translation by the herpes simplex virus type 1
immediate-early protein ICP27.

Ellison KS, Maranchuk RA, Mottet KL, Smiley JR.

Department of Medical Microbiology and Immunology, university of
Alberta, Edmonton, Alberta, Canada.

Herpes simplex virus (HSV) ICP27 is an essential and multifunctional
regulator of gene expression that modulates the synthesis and
maturation of viral and cellular mRNAs. Processes that are affected by
ICP27 include transcription, pre-mRNA splicing, polyadenylation, and
nuclear RNA export. We have examined how ICP27 influences the
expression of the essential HSV tegument protein and transactivator of
immediate-early gene expression VP16. We monitored the effects of ICP27
on the levels, nuclear export, and polyribosomal association of VP16
mRNA and on the amount and stability of VP16 protein. Deletion of ICP27
reduced the levels of VP16 mRNA without altering its nuclear export or
the stability of the encoded protein. However, the translational yield
of the VP16 mRNA produced in the absence of ICP27 was reduced 9- to
80-fold relative to that for wild-type infection, suggesting a defect
in translation. In the absence of ICP27, the majority of cytoplasmic
VP16 mRNA was not associated with actively translating polyribosomes
but instead cosedimented with 40S ribosomal subunits, indicating that
the translational defect is likely at the level of initiation. These
effects were mRNA specific, as polyribosomal analysis of two cellular
transcripts (glyceraldehyde-3-phosphate dehydrogenase and beta-actin)
and two early HSV transcripts (thymidine kinase and ICP8) indicated
that ICP27 is not required for efficient translation of these mRNAs.
Thus, we have uncovered a novel mRNA-specific translational regulatory
function of ICP27.


J Virol. 2001 May;75(9):4376-85. Related Articles, Links


Herpes simplex virus IE63 (ICP27) protein interacts with
spliceosome-associated protein 145 and inhibits splicing prior to the
first catalytic step.

Bryant HE, Wadd SE, Lamond AI, Silverstein SJ, Clements JB.

Division of Virology, Institute of Biomedical and Life Sciences,
University of Glasgow, Glasgow G11 5JR, Scotland, United Kingdom.

The multifunctional herpes simplex virus type 1 (HSV-1) protein IE63
(ICP27) interacts with the essential pre-mRNA splicing factor,
spliceosome-associated protein 145 (SAP145), and in infected cells IE63
and SAP145 colocalize. This interaction was reduced or abrogated
completely using extracts from cells infected with IE63 viral mutants,
with mutations in IE63 KH and Sm homology domains, which do not exhibit
host shutoff or inhibit splicing. In the presence of IE63, splicing in
vitro was inhibited prior to the first catalytic step and the B/C
complex formed during splicing was shifted up in mobility and reduced
in intensity. With the use of splicing extracts, IE63 and SAP145 both
comigrated with the B/C complex, suggesting that they interact within
this complex to inhibit B/C complex formation or conversion. The
inhibition of splicing may facilitate the export of viral or cellular
transcripts, possibly via other protein partners of IE63. These data
provide important new insights into how IE63 influences pre-mRNA
processing during HSV-1 infection.

PMID: 11287586 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/..586&query_hl=73

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It seems like L-canavanine is causing a delay of HSV into developing an
OB

Regulation of Herpesvirus Macromolecular Synthesis: Sequential
Transition of Polypeptide Synthesis Requires Functional Viral
Polypeptides

R=2E W. Honess and Bernard Roizman



It was previously shown that virus-specific polypeptides made in HEp-2
cells infected with herpes simplex 1 form three groups designated  , =DF
, and  whose synthesis is coordinately regulated and sequentially
ordered. This report shows that one or more functional  polypeptides
are necessary to turn on the synthesis of =DF and  groups, and
conversely, one or more polypeptides in the latter groups turn off the
synthesis of  polypeptides. Specifically, infected cells maintained in
medium containing either canavanine, an analogue of arginine, or
azetidine-2-carboxylic acid, an analogue of proline and hydroxyproline,
synthesized  polypeptide at rates comparable to maximal rates in
untreated infected cells but did not undergo the normal transition to
=DF and  polypeptide synthesis. The transition to  polypeptide synthesis
and shut-off of synthesis of earlier polypeptide groups proceeded
normally if addition of canavanine was delayed until at least 4-5 hr
after infection. Addition of canavanine after the onset of =DF and
polypeptide synthesis, i.e., between 2 and 3.5 hr after infection,
resulted in sustained, simultaneous synthesis of all three polypeptide
groups, a phenomenon not seen in untreated infected cells.
Canavanine-treated infected cells, synthesizing  polypeptides,
recovered the capacity to make =DF and  polypeptides after removal of
the analogue, but only after a 1- to 2-hr delay compared with infected
untreated cells. The data indicate that the on and off controls
inherent in the cascade regulation of viral polypeptide synthesis are
mediated by one or more polypeptides in each group at transcriptional
or post-transcriptional levels
http://www.pnas.org/cgi/reprint/72/4/1276

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"Although these data
could be interpreted in terms of interference between functional
and nonfunctional a polypeptides, we cannot presently
exclude alternative explanations, such as impairment of essential
host functions during the exposure to canavanine."
http://www.pnas.org/cgi/reprint/72/4/1276

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http://www.ucihs.uci.edu/microbio/i..ndriGoldin.html

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http://www.ncbi.nlm.nih.gov/entrez/..oldin+
r

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Herpes Simplex Virus Type 1 Protein IE63 Affects the Nuclear
Export of Virus Intron-Containing Transcripts

http://jvi.asm.org/cgi/reprint/70/8/5255

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Inhibition of Herpes Simplex Virus Replication by Succinyl
Concanavalin A

http://www.pubmedcentral.gov/picren..13&blobtype=pdf

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Accumulation of Herpes Simplex Virus Type 1 RNAs of Different
Kinetic Classes in the Cytoplasm of Infected Cells

http://www.pubmedcentral.nih.gov/pi..90&blobtype=pdf

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