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Journal of Virology, March 2000, p. 2481-2487, Vol. 74, No. 5
Department of Molecular Genetics and
Biochemistry, University of Pittsburgh School of Medicine,
Pittsburgh, Pennsylvania 15261
Received 30 September 1999/Accepted 24 November 1999
The use of herpes simplex virus (HSV) vectors for in vivo gene
therapy will require the targeting of vector infection to specific cell
types in certain in vivo applications. Because HSV glycoprotein D (gD)
imparts a broad host range for viral infection through recognition of
ubiquitous host cell receptors, vector targeting will require the
manipulation of gD to provide new cell recognition specificities in a
manner designed to preserve gD's essential role in virus entry. In
this study, we have determined whether an entry-incompetent HSV mutant
with deletions of all Us glycoproteins, including gD, can be
complemented by a foreign attachment/entry protein with a different
receptor-binding specificity, the vesicular stomatitis virus
glycoprotein G (VSV-G). The results showed that transiently expressed
VSV-G was incorporated into gD-deficient HSV envelopes and that the
resulting pseudotyped virus formed plaques on gD-expressing VD60 cells,
albeit at a 50-fold-reduced level compared to that of wild-type gD.
This reduction may be related to differences in the entry pathways used
by VSV and HSV or to the observed lower rate of incorporation of VSV-G
into virus envelopes than that of gD. The rate of VSV-G incorporation
was greatly improved by using recombinant molecules in which the
transmembrane domain of HSV glycoprotein B or D was substituted for
that of VSV-G, but these recombinant molecules failed to promote virus entry. These results show that foreign glycoproteins can be
incorporated into the HSV envelope during replication and that gD can
be dispensed with on the condition that a suitable attachment/entry
function is provided.
Viruses have been extensively used
for transferring genes into cells both in vitro and in vivo and remain
the most efficient tools available for gene therapy applications. The
ability of viruses to infect either specific cell types through
specific receptors or a broad range of cell types through common cell
surface determinants represents both advantages and limitations for the use of virus gene transfer systems. An important step forward in the
development of virus-mediated gene transfer will be the development of
methods to target viral infection to specific cell types, particularly
in vivo, in order to achieve gene delivery to the tissue where
transgene expression will be most effective in treating disease. The
achievement of this goal will require modification of the virus host
range by the manipulation of viral surface structures involved in cell
recognition without compromising virus entry and transgene expression.
Herpes simplex virus type 1 (HSV-1) has received considerable attention
as a gene transfer vector because of its large carrying capacity for
foreign DNA sequences (2, 35, 53) and its ability to package
vector DNA as concatemerized plasmids, referred to as amplicons
(18, 19, 60). More recently, replication-incompetent genomic
HSV vectors have been developed in which immediate-early (IE) functions
are deleted, which eliminates both early and late gene expression and
vector toxicity (36, 44, 56, 57, 69). Long-term transgene
expression has been achieved in neurons (24, 31, 39), the
natural host for latent viral infections, as well as in a variety of
other cell types in which defective HSV vectors can persist with
continued transgene expression (26; D. Wolfe,
W. F. Goins, T. J. Kaplan, S. Capuano, M. Murphey-Corb, and
J. C. Glorioso, submitted for publication; X. Zhang, J. P. Goff, D. S. Shields, J. Wechuck, R. J. R. Rouse, D. Wolfe, W. F. Goins, J. S. Greenberger, and J. C. Glorioso, submitted for publication). In addition, attenuated
replication-competent HSV vectors have been tested in clinical
applications. In these vectors, either the nonessential HSV-1 attachment is known to be mediated by multiple glycoproteins.
Binding to cell surface glycosaminoglycans, primarily heparan sulfate
(27, 28, 61, 70) but also dermatan sulfate (4,
67) and chondroitin sulfate (3), is mediated by
exposed domains of glycoproteins C (gC) (28, 40, 63, 65) and
B (gB) (29, 40). This binding represents about 85% of the
total binding to Vero cells, with gC contributing the major share
(28, 40). This initial stage of virus-cell contact is not
sufficient to trigger virus entry but accomplishes the task of
positioning the virus for interaction with receptors recognized by
glycoprotein D (gD). Recent work by several labs has identified gD
cognate receptors utilized for both virus attachment and penetration. The first identified herpesvirus entry mediator, HVEM or HveA, is a
member of the TNF- The consequence of the sequential attachment steps involving gB, gC,
and gD is the fusion of the virus envelope with the cell surface
membrane and subsequent virus entry. The events in penetration are not
well understood, but multiple glycoproteins are required. A role for gD
in virus penetration is supported by evidence that attached virus can
be neutralized by anti-gD antibody and that virus mutants with a
deletion of gD attach to cells but do not penetrate (17,
30). Mutants with a deletion of gH/gL or gB are also blocked in
virus penetration but are not defective in attachment. Both gB and gD
have been shown to be capable of inducing syncytia if expressed on the
cell surface at low pH, supporting a possible role for both molecules
in fusion (5). According to one model, gD, gB, and gH/gL act
in succession to mediate fusion, entry, and virus release into the
cytoplasm (16). The ability of gD to bind to receptors on a
broad range of cell types suggests that the partial or complete
replacement of gD with other sequences capable of mediating viral entry
may provide a means for HSV vector targeting.
The present study was designed to evaluate the G spike glycoprotein of
vesicular stomatitis virus (VSV-G) as a potential alternate to HSV gD
in binding and entry. VSV is a member of the rhabdovirus family of RNA
viruses. The VSV-G spike glycoprotein is involved in both virus
attachment and entry into receptor-bearing host cells (15, 41,
58). VSV-G enables receptor-mediated endocytosis of VSV
(47) and induces fusion of the viral envelope and the endosomal membrane (13, 14, 54), which results in the entry of VSV virions into the host cell cytoplasm. Although endocytosis involving VSV-G exposes the virus to a mildly acidic environment, several investigators have described VSV-G-mediated infection by other
viruses pseudotyped with VSV-G, including retroviruses (1, 43,
52), measles virus (62), and adenoviruses
(59).
Experiments were undertaken to determine (i) whether wild-type VSV-G or
chimeric VSV-G/HSV glycoprotein derivatives could be incorporated into
the envelope of gD-deficient HSV during virus replication and (ii)
whether VSV-G or the chimeric molecules could provide an alternative
means of HSV attachment and entry in lieu of gD. The results showed
that VSV-G and derivatives containing the transmembrane domain (TM) of
HSV gB or gD were incorporated into virus envelopes at high levels,
although only native VSV-G had the ability to mediate infection by a
gD-deficient virus. These studies demonstrate that VSV-G can substitute
for gD in promoting virus attachment and entry.
Construction of plasmids and viruses.
A 10.1-kb
KpnI fragment (HSV-1 positions 134789 to 144894) from the Us
region of the EcoRI H plasmid (25) was cloned
into the unique KpnI site of a pSP72 derivative lacking
BamHI sites to produce pUs. A 4.2-kb BamHI
fragment, containing a human cytomegalovirus IE
promoter-lacZ expression cassette from pIEP-lacZ
(2), was substituted for the 6.5-kb BamHI J
fragment of pUs to create pUs
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Pseudotyping of Glycoprotein D-Deficient Herpes
Simplex Virus Type 1 with Vesicular Stomatitis Virus Glycoprotein G
Enables Mutant Virus Attachment and Entry
ABSTRACT
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34.5 gene
product, which disables the double-stranded-RNA-dependent protein
kinase pathway involved in the inhibition of protein synthesis in
virus-infected cells (7, 10), or the 34.5 gene in
combination with the UL39 viral ribonucleotide reductase large subunit
(32, 49) was deleted to allow virus replication in dividing
cells (e.g., glioblastoma cells) but not in certain postmitotic cells
(e.g., brain neurons). However, the use of these attenuated viruses
remains subject to safety concerns since they can infect nontumor
cells, suggesting that their use may be limited to specialized
applications, such as with brain tumors. Because HSV has a very broad
host range, the utility of HSV vectors may be greatly increased by
restricting viral infection to the cell types of interest, particularly
in applications in which virus replication is required for effective gene delivery. Modification of the host range of HSV may prove to be a
formidable task, considering the complexity of the virus envelope and
the staged process of virus infection, requiring multiple essential
viral envelope components (6, 11, 33, 42). Nevertheless,
recent advances in understanding the viral envelope glycoproteins that
mediate virus attachment and penetration suggest that it may be
possible to target HSV infections.
/NGF receptor family (48, 50, 55, 64)
and has a restricted cell type distribution. A second receptor for gD,
HveC, is a member of the immunoglobulin superfamily and is widely
expressed (20, 37, 38), providing a basis for the broad host
range of HSV-1.
3-8Z, which contains sufficient
flanking sequences for recombination into wild-type virus. A gD-null
virus, KUs3-8Z (Fig. 1A), was generated by homologous recombination of wild-type KOS virus with pUs3-8Z. lacZ-expressing recombinants were identified by
staining with X-Gal [0.1%
5-bromo-4-chloro-3-indoyl-
-D-galactopyranoside (Roche,
Indianapolis, Ind.) in a solution containing 100 mM Tris-HCl (pH 8.0),
13.5% dimethyl formamide (Sigma, St. Louis, Mo.), 14 mM
K4Fe(CN)6, and 14 mM
K3Fe(CN)6], and a selected blue plaque was
purified in three rounds of limiting dilution. The resulting gD-null
virus could be propagated on gD-complementing VD60 cells (42) but was unable to form plaques on Vero cells. The
genotype of this virus was null for Us3 (protein kinase), Us4 (gG), Us5 (gJ), Us6 (gD), Us7 (gI), and Us8 (gE), as confirmed by the absence of
the 6.5-kb BamHI J fragment in a Southern blot analysis
(Fig. 1A). The extensive deletion of Us sequences precludes
recombination between the complementing gD gene of VD60 cells and the
KUs3-8Z viral genome. Southern blot analysis using a
lacZ-specific probe also verified the presence of the human
cytomegalovirus IEp-lacZ expression cassette in KUs3-8Z
(Fig. 1A).
View larger version (29K):
[in a new window]
FIG. 1.
Construction of the K Us3-8Z recombinant virus and
structure of the VSV-G/HSV chimeric proteins. (A) Schematic of the
HSV-1 genome depicting the location of the essential and nonessential
glycoprotein genes and replacement of the Us3-Us8 BamHI J
fragment of strain KOS by a lacZ expression cassette to
generate the gD-null virus KUs3-8Z. The accompanying Southern blots
demonstrate the presence in KUs3-8Z of the 4.2-kb lacZ
cassette (LacZ probe) and the absence of the 6.5-kb BamHI J
fragment (BamHI J probe). (B) Wild-type and chimeric proteins (kindly
provided by Hara P. Ghosh, McMaster University) represented as boxes
corresponding to the EC (left), TM (center), and CT (right), with the
relevant amino acid numbers provided in each case. VSV-G sequences are
shown as open boxes, HSV-1 gB sequences are shown as black boxes, and
HSV-1 gD sequences are shown as grey boxes. A deletion in the gB TM
creating the gB3 derivative is indicated.
Incorporation into budding viruses.
Previous studies examining
chimeric glycoproteins (22) identified sequences within the
TM of gB that are involved in localization of gB to the nuclear
envelope, a potential point of membrane acquisition for budding capsids
(21). Accordingly, we tested whether these sequences or
potentially equivalent sequences in gD (51) could anchor the
EC of VSV-G in the envelope of KUs3-8Z. 293T cells, in which the
adenovirus major late promoter is active, were plated on 60-mm dishes
and transfected with the wild-type or chimeric VSV-G, gD, or gB
plasmids using Lipofectamine (Life Technologies, Inc., Gaithersburg,
Md.). Twenty-four hours later, the cells were infected with KUs3-8Z
at a multiplicity of infection of 3 for 1.5 h. Two hours
postinfection (p.i.), the cells were treated for 1 min with 0.1 M
glycine, pH 3.0, to inactivate nonpenetrating virus, and were incubated
for 48 h at 37°C in Dulbecco modified Eagle medium-10% fetal
bovine serum (Life Technologies, Inc.) containing
[35S]methionine-cysteine (NEN-DuPont, Boston, Mass.).
Cell lysates (Fig. 2A) were prepared in
lysis buffer containing 20 mM Tris-HCl (pH 8.0), 150 mM NaCl, 1%
Triton X-100 (Roche), and 1 mM
N-p-tosyl-L-lysine chloromethyl ketone (TLCK)
(Roche) and were immunoprecipitated overnight at 4°C with antibodies
against HSV-1 gB (lanes B), gC (lanes C), gD (lanes D), or VSV (lanes
G) (30, 45, 46) (VSV polyclonal antibody kindly provided by
Patricia Whitaker-Dowling, University of Pittsburgh). Samples were
incubated for 1 h with protein A-Sepharose (Sigma) and centrifuged
at 500 × g, and the immune complexes were washed with
600 µl of lysis buffer and subjected to sodium dodecyl
sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). In addition,
media from the transfected, infected cultures were collected and
cleared of cell debris and cell-associated virus by centrifugation.
Virus from the cell supernatant was added to lysis buffer,
immunoprecipitated, and subjected to SDS-PAGE analysis.
|
Complementation of gD function in HSV-1 entry.
Using
pseudotyped viruses produced by the transient-expression protocol, we
determined whether VSV-G or any of the chimeric proteins could
complement the functions of gD in virus entry. 293T cells were
transfected with the panel of glycoprotein constructs, infected with
KUs3-8Z (multiplicity of infection = 3.0), treated with
glycine, and incubated in complete media for 48 h. Media were
collected and serial dilutions were incubated with 5 × 105 VD60 cells in suspension for 1.5 h before the
cells were plated in 35-mm dishes. Twelve hours p.i., the VD60 cells
were overlaid with complete media containing 0.5% methyl cellulose
(Aldrich, Milwaukee, Wis.), and at 72 h p.i., plaques were stained
with X-Gal and counted. Virions capable of mediating virus entry in the
absence of gD would produce plaques on VD60 cells, which constitutively express gD (42) and thereby provide the functions of gD
required for the progression from the initial entry to plaque
formation. Three experiments were performed in duplicate, and the
compiled results are shown in Fig. 3A.
Medium from mock-transfected cells yielded a background of less than 10 PFU, presumably representing gD-complemented KUs3-8Z
virus remaining from the initial 293T-cell infection despite the
subsequent acidic glycine wash. The wild-type gD plasmid produced a
robust level of complementation (5 × 103 PFU), but of
the other constructs tested, only the VSV-G plasmid displayed
complementing activity above background (~100 PFU). While the
complementation level of VSV-G was 50-fold lower than that of gD, the
ability of this foreign glycoprotein to reproducibly substitute for gD
in entry represents the first demonstration of an infectious,
pseudotyped gD-null HSV-1 particle.
|
Neutralization of complementing virus. To validate these results, VD60 infectivity assays were repeated after incubation of the 293T media with complement-dependent neutralizing antibodies against HSV-1 glycoproteins (gB, gC, or gD) or VSV-G. Serial dilutions of virus-containing media were incubated with 5 µl of human complement (Life Technologies, Inc.) in the presence or absence of each antibody (2 µl) for 2 h at 37°C. VD60 cells (5 × 105) were added to each sample and incubated in suspension for 1.5 h at 37°C with shaking. Infected cells were plated in 35-mm dishes, treated at 2 h p.i. with 0.1 M glycine as before, and overlaid with complete media containing methyl cellulose. Seventy-two hours p.i., plaques were stained with X-Gal and counted. The results are tabulated in Fig. 3B.
As shown in Fig. 3B, monoclonal antibodies against gB were able to neutralize all samples; likewise, neutralization of all samples was observed with gC-specific antibodies (data not shown), as was expected since KUs3-8Z is wild type for both gB and gC. Antibodies against gD
completely neutralized wild-type-gD-complemented as well as
mock-complemented virus, supporting the earlier suggestion that the
background in this assay was due to gD-complemented KUs3-8Z remaining from the initial 293T-cell infection. The gD antibodies were
also able to neutralize 18% of the activity in the VSV-G-complemented preparation, which is somewhat more than the expected neutralization of
the background (4%) and may be due to nonspecific interactions. Likewise, anti-VSV-G polyclonal antibodies were able to neutralize 91%
of the complementation by VSV-G but also displayed some neutralization of gD-complemented material (13%). These results validated the conclusion that VSV-G has a measurable, albeit limited, ability to
complement the entry functions of HSV gD in a transient assay.
HSV shows great promise as a generally useful vector for the in vivo
delivery of genes to a variety of cells, including bone marrow stem
cells and cells of the nervous system, muscle, connective tissue,
liver, and endothelium (2, 23, 26, 66, 68, 71; Wolfe
et al., submitted). While the virus naturally persists in a latent
state in sensory neurons, highly defective mutant viruses can also
persist in other cell types (26; Wolfe et al., submitted; Zhang et al., submitted). HSV vectors can be targeted to
specific sites in the body by direct injection, but there are circumstances in which safe and effective gene therapy will require cell-type-specific virus infection. Because natural HSV receptors that
mediate virus entry are found on most cell types (e.g., HveC), it will
be important to mutate the virus to prevent its attachment to these
natural receptors and to equip the particle instead with ligands for
cell-type-specific receptors.
The present study was initiated to determine whether gD is unique in
its ability to mediate HSV entry or whether functionally related
proteins from other viruses can substitute for gD, provided they are
incorporated into the HSV envelope. We chose to test VSV-G because this
protein has been used with considerable success for pseudotyping other
viruses (1, 43, 52, 59, 62) and mediates both attachment and
penetration of VSV (15, 41, 58). Nevertheless, VSV-G was not
ideal, since the sites of HSV and VSV budding differ, raising the
concern that VSV-G might not be incorporated into HSV envelopes.
Moreover, since VSV entry involves fusion with endosomal vesicle
membranes, which exposes the virus to an acidic environment, while HSV
fuses with the cell surface membrane, VSV-G-directed entry could result
in the destruction of the HSV particles in the endosomes. Remarkably,
we found that VSV-G was included in the HSV envelope, although less
abundantly than wild-type gD. Anticipating inefficient incorporation,
we simultaneously tested chimeric constructs utilizing gB or gD
sequences to direct the VSV-G EC to the HSV envelope. The results
showed that the incorporation of VSV-G into virus was greatly improved when the TM of gB or gD was substituted for that of VSV-G, but these
chimeric molecules were unable to direct HSV entry. The incorporation
of unmodified VSV-G into virus may be accomplished by a membrane
exchange in the Golgi apparatus or with the plasma membrane during
virus egress (8, 9, 34), raising the possibility that
expression during HSV infection may be sufficient for the inclusion of
foreign glycoproteins in mature virus envelopes. Accordingly, other
viral proteins may also be correctly sorted and incorporated into
mature HSV virions, which would offer a range of opportunities for
pseudotyping HSV-1 particles with non-HSV viral proteins. This
suggestion is supported by the previous demonstration that cellular CD4
can be incorporated into HSV virions, albeit at low levels
(12).
Although the amount of VSV-G in pseudotyped HSV envelopes was
relatively low, VSV-G was able to mediate sufficient virus entry to
allow plaque formation on VD60 cells. VD60 cells provide gD intracellularly for incorporation into genotypically gD-deficient virus, in this case replacing VSV-G, which was not produced by either
the virus or the host cells. However, these events require prior entry
of the virus into single cells, and the VD60 plaque assay therefore
measured the success of this initial infection with pseudotyped gD-null
virus, using intracellular gD to convert single infected cells into
plaques. The assay showed a reproducible increase in plaque formation
by the VSV-G-pseudotyped virus over the background level observed with
mock-complemented virus and showed a return to background levels when
the pseudotyped virus was preincubated with VSV-G- but not
gD-neutralizing antibodies. The gC-specific antibodies neutralized all
plaque-forming activity, including the background, while gD antibodies
removed only a fraction, consistent with the interpretation that the
background represented residual gD-complemented virus from the
293T-cell infection preceding the assembly of pseudotyped virus. These
results, representing the first demonstration of an infectious gD-null
HSV-1 particle, have now been confirmed using a VSV-G/KUs3-8Z
recombinant virus (W. F. Goins et al., unpublished data).
Preliminary experiments indicate that this recombinant virus enters by
fusion with endosomal vesicles, like VSV but unlike wild-type HSV.
Given this altered entry pathway, contributions from any HSV
glycoprotein normally functioning in HSV infection may be dispensable
in the presence of VSV-G, suggesting possibilities to examine regarding
the roles of these glycoproteins, including gD, in postentry events
such as budding and axonal transport.
The suggestion from our work that the entry pathway of HSV can be
fundamentally altered by replacing gD with a foreign viral glycoprotein
indicates that there is considerable flexibility in the mechanism of
HSV entry, which in turn suggests that other foreign glycoproteins
could be equally or more effective substitutes for gD. Among these,
some may restrict the viral host range or represent attractive targets
for the engineering of new host cell specificities. Our work suggests
the intriguing possibility that gD-null HSV can be pseudotyped with
separate molecules providing the cell recognition and fusion functions,
reminiscent of the natural situation among paramyxoviruses, which could
greatly facilitate the creation of targeting vectors.
| |
ACKNOWLEDGMENTS |
|---|
We thank Hara P. Ghosh for providing the VSV-G and VSV-G/HSV chimeric constructs, Patricia Dowling for providing the VSV antibody, and David Johnson for providing the VD60 cell line. We thank Tom Holland, Patricia Dowling, Julius Youngner, and Darren Wolfe for helpful discussions.
This work was supported by Public Health Service grant R01-66141 from the National Institutes of Health (J.C.G.).
| |
FOOTNOTES |
|---|
* Corresponding author. Mailing address: Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, E1240 Biomedical Science Tower, Pittsburgh, PA 15261. Phone: (412) 648-8106. Fax: (412) 624-8997. E-mail: glorioso+{at}pitt.edu.
Present address: Onyx Pharmaceuticals, Richmond, CA 94806.
| |
REFERENCES |
|---|
|
Top
Abstract
Text
References
|
|---|
| 1. |
Abe, A.,
S.-T. Chen,
A. Miyanohara, and T. Friedmann.
1998.
In vitro cell-free conversion of noninfectious Moloney retrovirus particles to an infectious form by the addition of the vesicular stomatitis virus surrogate envelope G protein.
J. Virol.
72:6356-6361 |
| 2. | Akkaraju, G. R., J. Huard, E. P. Hoffman, W. F. Goins, R. Pruchnic, S. C. Watkins, J. B. Cohen, and J. C. Glorioso. 1999. Herpes simplex virus vector-mediated dystrophin gene transfer and expression in MDX mouse skeletal muscle. J. Gene Med. 1:280-289[CrossRef][Medline]. |
| 3. | Banfield, B., Y. Leduc, L. Esford, R. Visalli, C. Brandt, and F. Tufaro. 1995. Evidence for an interaction of herpes simplex virus with chondroitin sulfate proteoglycans during infection. Virology 208:531-539[CrossRef][Medline]. |
| 4. |
Banfield, B. W., and F. Tufaro.
1990.
Herpes simplex virus particles are unable to traverse the secretory pathway in the mouse L-cell mutant gro29.
J. Virol.
64:5716-5729 |
| 5. |
Butcher, M.,
K. Raviprakash, and H. P. Ghosh.
1990.
Acid pH-induced fusion of cells by herpes simplex virus glycoproteins gB and gD.
J. Biol. Chem.
265:5862-5868 |
| 6. |
Cai, W.,
B. Gu, and S. Person.
1988.
Role of glycoprotein B of herpes simplex virus type 1 in viral entry and cell fusion.
J. Virol.
62:2596-2604 |
| 7. |
Chambers, R.,
G. Y. Gillespie,
L. Soroceanu,
S. Andreansky,
S. Chatterjee,
J. Chou,
B. Roizman, and R. Whitley.
1995.
Comparison of genetically engineered herpes simplex viruses for the treatment of brain tumors in a scid mouse model of human malignant glioma.
Proc. Natl. Acad. Sci. USA
92:1411-1415 |
| 8. | Chatterjee, S., and S. Sarkar. 1992. Studies on endoplasmic reticulum-Golgi complex cycling pathway in herpes simplex virus-infected and brefeldin A-treated human fibroblast cells. Virology 191:327-337[CrossRef][Medline]. |
| 9. |
Cheung, P.,
B. W. Banfield, and F. Tufaro.
1991.
Brefeldin A arrests the maturation and egress of herpes simplex virus particles during infection.
J. Virol.
65:1893-1904 |
| 10. |
Chou, J.,
J. Chen,
M. Gross, and B. Roizman.
1995.
Association of a M(r) 90,000 phosphoprotein with protein kinase PKR in cells exhibiting enhanced phosphorylation of translation initiation factor eIF-2 alpha and premature shutoff of protein synthesis after infection with gamma 134.5 mutants of herpes simplex virus 1.
Proc. Natl. Acad. Sci. USA
92:10516-10520 |
| 11. |
Desai, P.,
P. Schaffer, and A. Minson.
1988.
Excretion of non-infectious virus particles lacking glycoprotein H by a temperature-sensitive mutant of herpes-simplex virus type 1: evidence that gH is essential for virion infectivity.
J. Gen. Virol.
69:1147-1156 |
| 12. |
Dolter, K. E.,
S. R. King, and T. C. Holland.
1993.
Incorporation of CD4 into virions by a recombinant herpes simplex virus.
J. Virol.
67:189-195 |
| 13. | Fan, D. P., and B. M. Sefton. 1978. The entry into host cells of Sindbis virus, vesicular stomatitis virus and Sendai virus. Cell 15:985-992[CrossRef][Medline]. |
| 14. |
Florkiewicz, R. Z., and J. K. Rose.
1984.
A cell line expressing vesicular stomatitis virus glycoprotein fuses at low pH.
Science
225:721-723 |
| 15. | Fredericksen, B. L., and M. A. Whitt. 1996. Mutations at two conserved acidic amino acids in the glycoprotein of vesicular stomatitis virus affect pH-dependent conformational changes and reduce the pH threshold for membrane fusion. Virology 217:49-57[CrossRef][Medline]. |
| 16. |
Fuller, A. O., and W.-C. Lee.
1992.
Herpes simplex virus type 1 entry through a cascade of virus-cell interactions requires different roles of gD and gH in penetration.
J. Virol.
66:5002-5012 |
| 17. |
Fuller, A. O., and P. G. Spear.
1985.
Specificities of monoclonal and polyclonal antibodies that inhibit adsorption of herpes simplex virus to cells and lack of inhibition by potent neutralizing antibodies.
J. Virol.
55:475-482 |
| 18. |
Geller, A., and X. Breakefield.
1988.
A defective HSV-1 vector expresses Escherichia coli -galactosidase in cultured peripheral neurons.
Science
241:1667-1669 |
| 19. |
Geller, A.,
K. Keyomarsi,
J. Bryan, and A. Pardee.
1990.
An efficient deletion mutant packaging system for defective herpes simplex virus vectors: potential applications to human gene therapy and neuronal physiology.
Proc. Natl. Acad. Sci. USA
87:8950-8954 |
| 20. |
Geraghty, R. J.,
C. Krummenacher,
G. H. Cohen,
R. J. Eisenberg, and P. G. Spear.
1998.
Entry of alphaherpesviruses mediated by poliovirus receptor-related protein 1 and poliovirus receptor.
Science
280:1618-1620 |
| 21. | Gilbert, R., and H. P. Ghosh. 1993. Immunoelectron microscopic localization of herpes simplex virus glycoprotein gB in the nuclear envelope of infected cells. Virus Res. 28:217-231[CrossRef][Medline]. |
| 22. |
Gilbert, R.,
K. Ghosh,
L. Rasile, and H. P. Ghosh.
1994.
Membrane anchoring domain of herpes simplex virus glycoprotein gB is sufficient for nuclear envelope localization.
J. Virol.
68:2272-2285 |
| 23. |
Goins, W. F.,
K. A. Lee,
J. D. Cavalcoli,
M. E. O'Malley,
S. T. DeKosky,
D. J. Fink, and J. C. Glorioso.
1999.
Herpes simplex virus type 1 vector-mediated expression of nerve growth factor protects dorsal root ganglion neurons from peroxide toxicity.
J. Virol.
73:519-532 |
| 24. |
Goins, W. F.,
L. R. Sternberg,
K. D. Croen,
P. R. Krause,
R. L. Hendricks,
D. J. Fink,
S. E. Straus,
M. Levine, and J. C. Glorioso.
1994.
A novel latency-active promoter is contained within the herpes simplex virus type 1 UL flanking repeats.
J. Virol.
68:2239-2252 |
| 25. |
Goldin, A. L.,
R. M. Sandri-Goldin,
M. Levine, and J. C. Glorioso.
1981.
Cloning of herpes simplex virus type 1 sequences representing the whole genome.
J. Virol.
38:50-58 |
| 26. | Gomez-Navarro, J., J. L. Contreras, W. Arafat, X. L. Jiang, D. M. Krisky, T. Oligino, P. Marconi, W. Arafat, B. Hubbard, J. C. Glorioso, D. T. Curiel, and J. M. Thomas. Genetically modified CD34+ cells as cellular vehicles for gene delivery into areas of angiogenesis in a Rhesus model. Gene Ther., in press. |
| 27. |
Gruenheid, S.,
L. Gatzke,
H. Meadows, and F. Tufaro.
1993.
Herpes simplex virus infection and propagation in a mouse L cell mutant lacking heparan sulfate proteoglycans.
J. Virol.
67:93-100 |
| 28. |
Herold, B.,
R. Visalli,
N. Susmarski,
C. Brandt, and P. Spear.
1994.
Glycoprotein C-independent binding of herpes simplex virus to cells requires cell surface heparan sulfate and glycoprotein B.
J. Gen. Virol.
75:1211-1222 |
| 29. | Herold, B. C., S. I. Gerber, T. Polonsky, B. J. Belval, P. N. Shaklee, and K. Holme. 1995. Identification of structural features of heparin required for inhibition of herpes simplex virus type 1 binding. Virology 206:1108-1116[CrossRef][Medline]. |
| 30. |
Highlander, S. L.,
S. L. Sutherland,
P. J. Gage,
D. C. Johnson,
M. Levine, and J. C. Glorioso.
1987.
Neutralizing monoclonal antibodies specific for herpes simplex virus glycoprotein D inhibit virus penetration.
J. Virol.
61:3356-3364 |
| 31. |
Ho, D. Y., and E. S. Mocarski.
1989.
Herpes simplex virus latent RNA (LAT) is not required for latent infection in the mouse.
Proc. Natl. Acad. Sci. USA
86:7596-7600 |
| 32. |
Hunter, W. D.,
R. L. Martuza,
F. Feigenbaum,
T. Todo,
T. Mineta,
T. Yazaki,
M. Toda,
J. T. Newsome,
R. C. Platenberg,
H. J. Manz, and S. D. Rabkin.
1999.
Attenuated, replication-competent herpes simplex virus type 1 mutant G207: safety evaluation of intracerebral injection in nonhuman primates.
J. Virol.
73:6319-6326 |
| 33. |
Hutchinson, L.,
H. Browne,
V. Wargent,
N. Davis-Poynter,
S. Primorac,
K. Goldsmith,
A. C. Minson, and D. C. Johnson.
1992.
A novel herpes simplex virus glycoprotein, gL, forms a complex with glycoprotein H (gH) and affects normal folding and surface expression of gH.
J. Virol.
66:2240-2250 |
| 34. |
Johnson, D. C., and P. G. Spear.
1982.
Monensin inhibits the processing of herpes simplex virus glycoproteins, their transport to the cell surface, and the egress of virions from infected cells.
J. Virol.
43:1102-1112 |
| 35. | Krisky, D. M., P. C. Marconi, T. J. Oligino, R. J. D. Rouse, D. J. Fink, J. B. Cohen, S. C. Watkins, and J. C. Glorioso. 1998. Development of herpes simplex virus replication defective multigene vectors for combination gene therapy applications. Gene Ther. 5:1517-1530[CrossRef][Medline]. |
| 36. | Krisky, D. M., D. Wolfe, W. F. Goins, P. C. Marconi, R. Ramakrishnan, M. Mata, R. J. D. Rouse, D. J. Fink, and J. C. Glorioso. 1998. Deletion of multiple immediate early genes from herpes simplex virus reduces cytotoxicity and permits long-term gene expression in neurons. Gene Ther. 5:1593-1603[CrossRef][Medline]. |
| 37. |
Krummenacher, C.,
A. V. Nicola,
J. C. Whitbeck,
H. Lou,
W. Hou,
J. D. Lambris,
R. J. Geraghty,
P. G. Spear,
G. H. Cohen, and R. J. Eisenberg.
1998.
Herpes simplex virus glycoprotein D can bind to poliovirus receptor-related protein 1 or herpesvirus entry mediator, two structurally unrelated mediators of virus entry.
J. Virol.
72:7064-7074 |
| 38. |
Krummenacher, C.,
A. H. Rux,
J. C. Whitbeck,
M. Ponce-de-Leon,
H. Lou,
I. Baribaud,
W. Hou,
C. Zou,
R. J. Geraghty,
P. G. Spear,
R. J. Eisenberg, and G. H. Cohen.
1999.
The first immunoglobulin-like domain of HveC is sufficient to bind herpes simplex virus gD with full affinity, while the third domain is involved in oligomerization of HveC.
J. Virol.
73:8127-8137 |
| 39. | Lachmann, R. H., and S. Efstathiou. 1997. Utilization of the herpes simplex virus type 1 latency-associated regulatory region to drive stable reporter gene expression in the nervous system. J. Virol. 71:3197-3207[Abstract]. |
| 40. |
Laquerre, S.,
R. Argnani,
D. B. Anderson,
S. Zucchini,
R. Manservigi, and J. C. Glorioso.
1998.
Heparan sulfate proteoglycan binding by herpes simplex virus type 1 glycoproteins B and C, which differ in their contributions to virus attachment, penetration, and cell-to-cell spread.
J. Virol.
72:6119-6130 |
| 41. |
Li, Y.,
C. Drone,
E. Sat, and H. P. Ghosh.
1993.
Mutational analysis of the vesicular stomatitis virus glycoprotein G for membrane fusion domains.
J. Virol.
67:4070-4077 |
| 42. |
Ligas, M. W., and D. C. Johnson.
1988.
A herpes simplex virus mutant in which glycoprotein D sequences are replaced by -galactosidase sequences binds to but is unable to penetrate into cells.
J. Virol.
62:1486-1494 |
| 43. | Manning, W. C., J. E. Murphy, D. J. Jolly, S. J. Mento, and R. O. Ralston. 1998. Use of a recombinant murine cytomegalovirus expressing vesicular stomatitis virus G protein to pseudotype retroviral vectors. J. Virol. Methods 73:31-39[CrossRef][Medline]. |
| 44. |
Marconi, P.,
D. Krisky,
T. Oligino,
P. L. Poliani,
R. Ramakrishnan,
W. F. Goins,
D. J. Fink, and J. C. Glorioso.
1996.
Replication-defective HSV vectors for gene transfer in vivo.
Proc. Natl. Acad. Sci. USA
93:11319-11320 |
| 45. |
Marlin, S. D.,
S. L. Highlander,
T. C. Holland,
M. Levine, and J. C. Glorioso.
1986.
Antigenic variation (mar mutations) in herpes simplex virus glycoprotein B can induce temperature-dependent alterations in gB processing and virus production.
J. Virol.
59:142-153 |
| 46. |
Marlin, S. D.,
T. C. Holland,
M. Levine, and J. C. Glorioso.
1985.
Epitopes of herpes simplex virus type 1 glycoprotein gC are clustered in two distinct antigenic sites.
J. Virol.
53:128-136 |
| 47. | Matlin, K. S., H. Reggio, A. Helenius, and K. Simons. 1982. Pathway of vesicular stomatitis virus entry leading to infection. J. Mol. Biol. 156:609-631[CrossRef][Medline]. |
| 48. | Mauri, D. N., R. Ebner, R. I. Montgomery, K. D. Kochel, T. C. Cheung, G. L. Yu, S. Ruben, M. Murphy, R. J. Eisenberg, G. H. Cohen, P. G. Spear, and C. F. Ware. 1998. LIGHT, a new member of the TNF superfamily, and lymphotoxin alpha are ligands for herpesvirus entry mediator. Immunity 8:21-30[CrossRef][Medline]. |
| 49. |
Mineta, T.,
S. Rabkin, and R. Martuza.
1994.
Treatment of malignant gliomas using ganciclovir-hypersensitive, ribonucleotide reductase-deficient herpes simplex viral mutant.
Cancer Res.
54:3963-3966 |
| 50. | Montgomery, R. I., M. S. Warner, B. J. Lum, and P. G. Spear. 1996. Herpes simplex virus 1 entry into cells mediated by a novel member of the TNF/NGF receptor family. Cell 87:427-436[CrossRef][Medline]. |
| 51. | Odell, D., E. Wanas, J. Yan, and H. P. Ghosh. 1997. Influence of membrane anchoring and cytoplasmic domains on the fusogenic activity of vesicular stomatitis virus glycoprotein G. J. Virol. 71:7996-8000[Abstract]. |
| 52. |
Ory, D. S.,
B. A. Neugeboren, and R. C. Mulligan.
1996.
A stable human-derived packaging cell line for production of high titer retrovirus/vesicular stomatitis virus G pseudotypes.
Proc. Natl. Acad. Sci. USA
93:11400-11406 |
| 53. | Rasty, S., P. Poliani, D. Fink, and J. Glorioso. 1997. Deletion of the S component inverted repeat sequence c' and the nonessential genes Us1 through Us5 from the herpes simplex virus type 1 genome substantially impairs productive viral infection in cell culture and pathogenesis in the rat central nervous system. J. Neurovirol. 3:247-264[Medline]. |
| 54. | Riedel, H., C. Kondor-Koch, and H. Garoff. 1984. Cell surface expression of fusogenic vesicular stomatitis virus G protein from cloned cDNA. EMBO J. 3:1477-1483[Medline]. |
| 55. |
Rux, A. H.,
S. H. Willis,
A. V. Nicola,
W. Hou,
C. Peng,
H. Lou,
G. H. Cohen, and R. J. Eisenberg.
1998.
Functional region IV of glycoprotein D from herpes simplex virus modulates glycoprotein binding to the herpesvirus entry mediator.
J. Virol.
72:7091-7098 |
| 56. | Samaniego, L. A., N. Wu, and N. A. DeLuca. 1997. The herpes simplex virus immediate-early protein ICP0 affects transcription from the viral genome and infected-cell survival in the absence of ICP4 and ICP27. J. Virol. 71:4614-4625[Abstract]. |
| 57. |
Samaniego, L. A.,
L. Neiderhiser, and N. A. DeLuca.
1998.
Persistence and expression of the herpes simplex virus genome in the absence of immediate-early proteins.
J. Virol.
72:3307-3320 |
| 58. |
Schlegel, R.,
M. C. Willingham, and I. H. Pastan.
1982.
Saturable binding sites for vesicular stomatitis virus on the surface of Vero cells.
J. Virol.
43:871-875 |
| 59. |
Schneider, M.,
F. L. Graham, and L. Prevec.
1989.
Expression of the glycoprotein of vesicular stomatitis virus by infectious adenovirus vectors.
J. Gen. Virol.
70:417-427 |
| 60. | Spaete, R., and N. Frenkel. 1982. The herpes simplex virus amplicon: a new eucaryotic defective-virus cloning amplifying vector. Cell 30:295-304[CrossRef][Medline]. |
| 61. | Spear, P. G., M. T. Shieh, B. C. Herold, D. WuDunn, and T. I. Koshy. 1992. Heparan sulfate glycosaminoglycans as primary cell surface receptors for herpes simplex virus. Adv. Exp. Med. Biol. 313:341-353[Medline]. |
| 62. |
Spielhofer, P.,
T. Bächi,
T. Fehr,
G. Christiansen,
R. Cattaneo,
K. Kaelin,
M. A. Billeter, and H. Y. Naim.
1998.
Chimeric measles viruses with a foreign envelope.
J. Virol.
72:2150-2159 |
| 63. | Tal-Singer, R., C. Peng, M. Ponce de Leon, W. R. Abrams, B. W. Banfield, F. Tufaro, G. H. Cohen, and R. J. Eisenberg. 1995. Interaction of herpes simplex virus glycoprotein gC with mammalian cell surface molecules. J. Virol. 69:4471-4483[Abstract]. |
| 64. |
Terry-Allison, T.,
R. I. Montgomery,
J. C. Whitbeck,
R. Xu,
G. H. Cohen,
R. J. Eisenberg, and P. G. Spear.
1998.
HveA (herpesvirus entry mediator A), a coreceptor for herpes simplex virus entry, also participates in virus-induced cell fusion.
J. Virol.
72:5802-5810 |
| 65. |
Trybala, E.,
T. Berghtrom,
B. Svennerholm,
S. Jeansson,
J. C. Glorioso, and S. Olufsson.
1994.
Localization of the functional site in herpes simplex virus type 1 glycoproteins C involved in binding to cell surface heparan sulfate.
J. Gen. Virol.
75:743-752 |
| 66. | Weir, J. P., E. J. Dacquel, and J. Aronovitz. 1996. Herpesvirus vector-mediated gene delivery to human monocytes. Hum. Gene Ther. 7:1331-1338[Medline]. |
| 67. | Williams, R. K., and S. E. Straus. 1997. Specificity and affinity of binding of herpes simplex virus type 2 glycoprotein B to glycosaminoglycans. J. Virol. 71:1375-1380[Abstract]. |
| 68. |
Wilson, S. P.,
D. C. Yeomans,
M. A. Bender,
Y. Lu,
W. F. Goins, and J. C. Glorioso.
1999.
Antihyperalgesic effects of infection with a preproenkephalin-encoding herpes virus.
Proc. Natl. Acad. Sci. USA
96:3211-3216 |
| 69. | Wu, N., S. C. Watkins, P. A. Schaffer, and N. A. DeLuca. 1996. Prolonged gene expression and cell survival after infection by a herpes simplex virus mutant defective in the immediate-early genes encoding ICP4, ICP27, and ICP22. J. Virol. 70:6358-6369[Abstract]. |
| 70. |
WuDunn, D., and P. G. Spear.
1989.
Initial interaction of herpes simplex virus with cells is binding to heparan sulfate.
J. Virol.
63:52-58 |
| 71. |
Yamada, M.,
T. Oligino,
M. Mata,
J. R. Goss,
J. C. Glorioso, and D. J. Fink.
1999.
HSV vector-mediated expression of Bcl-2 prevents 6-hydroxydopamine induced degeneration of neurons in the substantia nigra in vivo.
Proc. Natl. Acad. Sci. USA
96:4078-4083 |
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