Previous Article | Next Article 
Journal of Virology, February 1999, p. 1695-1698, Vol. 73, No. 2
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Nonstructural C Protein Is Required for Efficient
Measles Virus Replication in Human Peripheral Blood Cells
Carine
Escoffier,1
Serge
Manié,1
Séverine
Vincent,1
Claude
P.
Muller,2
Martin
Billeter,3 and
Denis
Gerlier1,*
Immunité et Infections Virales, IVMC,
CNRS-UCBL, UMR 5537, 69372 Lyon Cedex 08, France1;
Laboratoire National de
Santé, Département d'Immunologie, L-1011 Luxembourg
BP1102, Luxembourg2; and
Institut
für Molekularbiologie, Universität Zürich, CH-8093
Zürich, Switzerland3
Received 26 June 1998/Accepted 2 November 1998
 |
ABSTRACT |
The P gene of measles virus (MV) encodes the phosphoprotein, a
component of the virus ribonucleoprotein complex, and two nonstructural proteins, C and V, with unknown functions. Growth of recombinant MV,
defective in C or V expression, was explored in human peripheral blood
mononuclear cells (PBMC). The production of infectious recombinant MV
V
was comparable to that of parental MV tag in simian
Vero fibroblasts and in PBMC. In contrast, MV C progeny
was strongly reduced in PBMC but not in Vero cells. Consistently, the
expression of both hemagglutinin and fusion proteins, as well as that
of nucleoprotein mRNA, was lower in MV C-infected PBMC.
Thus, efficient replication of MV in natural host cells requires the
expression of the nonstructural C protein. The immunosuppression that
accompanies MV infection is associated with a decrease in the in vitro
lymphoproliferative response to mitogens. MV C was as
potent as MV tag or MV V in inhibiting the
phytohemagglutinin-induced proliferation of PBMC, indicating that
neither the C protein nor the V protein is directly involved in this effect.
| |
TEXT |
Measles virus (MV), a member of the
Morbillivirus genus of the Paramyxoviridae
family, is an enveloped virus with a negative-strand RNA genome of
15,894 nucleotides. The genome encodes six structural proteins: the
nucleoprotein (N; 60 kDa), the phosphoprotein (P; 70 kDa), the matrix
(M) protein (37 kDa), the hemagglutinin (H) protein (80 kDa), the
fusion (F) protein (made of two subunits, F1 [40 kDa] and
F2 [20 kDa], by cleavage of the F0 precursor
[60 kDa]), and the large (L) protein (250 kDa) (2). The P
cistron also encodes the nonstructural proteins C (21 kDa), V (46 kDa), and R (40 kDa), but their functions are at present unclear (2, 14).
All members of the Paramyxovirus and
Morbillivirus genera express the C proteins, which are
relatively small basic proteins (less than 220 residues). They are
expressed from an alternate open reading frame overlapping the
N-terminal portion of the P gene. The translation of MV C protein is
initiated at the second AUG, which lies 22 nucleotides downstream of
the P start codon (1). The MV C protein has been localized
by immunofluorescence to the nucleus and cytoplasmic inclusions within
infected cells (1). A recombinant MV mutant with abrogated
expression of the C protein, MV C, has been shown to
replicate as efficiently as wild-type MV in simian Vero fibroblasts
(15).
The V protein, expressed by all members of the
Paramyxoviridae family except the Pneumovirus
genus and human parainfluenza virus type 1, results from an RNA editing
mechanism of the P gene. An insertion of a nontemplated G residue at
position 751 in the MV P cistron leads to the synthesis of the V
protein, which has 231 N-terminal amino acids in common with the P
protein and 68 unique C-terminal amino acids rich in cysteine residues
(4). The V protein is localized in the cytoplasm and, like
the P protein, is phosphorylated (23). Because of their
common sequence with the P protein and their well-conserved zinc
finger-like cysteine-rich domains, V proteins are suspected to play a
role in RNA synthesis. However, a recombinant MV defective in V
protein, MV V, grows as well as the wild-type virus in
simian Vero cells (19).
To delineate the roles of C and V proteins in other members of the
Paramyxoviridae family, a similar approach using recombinant virus with inactivated C or V genes has been undertaken. The P gene of
the Sendai virus, which belongs to the Respirovirus genus, encodes four C proteins (C', C, Y1, and Y2). Although a recombinant Sendai virus with a point mutation in C proteins was found to grow much
better than its progenitor virus in cell culture, it was avirulent when
inoculated into mice (8). In this virus, two RNA edition
processes of the P gene result in the synthesis of V and W proteins. A
recombinant V W+ Sendai virus replicated
normally in BHK cells and embryonated chicken eggs (6).
Replication of recombinant Sendai virus defective in both V and W
protein is enhanced in some cell lines but not in others
(12) and is strongly attenuated in vivo (12). A virus encoding V protein with its unique C-terminal sequence deleted displayed a wild-type phenotype in vitro and almost the same phenotype as V Sendai virus in vivo (13), suggesting an
important role for the cysteine-rich domain of V in Sendai virus virulence.
The discrepancies observed in vitro and in vivo in the roles of Sendai
virus C and V proteins in virus replication raised the possibility that
their effects are restricted to some tissues. MV infection of
peripheral blood mononuclear cells (PBMC) is likely to play a crucial
role in the MV-induced pathogenesis observed in humans. Indeed, PBMC
are thought to mediate the in vivo spreading of MV to lymphoid organs
(24). In vitro, the lymphoproliferative response to mitogens
of MV-infected cells is strongly decreased (20). This
impaired cellular response might participate in the immunodepression
observed in infected patients (cf. reference 10 for
a review). This led us to investigate the replication of recombinant MV
C and MV V in human PBMC.
Production of infectious MV C particles is restricted
in human PBMC but not in Vero cells.
Human PBMC were isolated from
heparinized venous blood of healthy donors by density gradient
centrifugation on Ficoll and cultured in RPMI 1640 supplemented with
10% fetal calf serum, 50 µg of gentamicin/ml, and 5 mM glutamine.
Cells were infected at a multiplicity of infection (MOI) of 1 for
1 h at 37°C with either parental recombinant MV tag (derived
from the Edmonston strain), MV C, or MV V
(15, 16, 19). Unadsorbed virus was washed out once with fresh medium, and the cells were incubated at 37°C in a 7%
CO2 incubator in the presence of 20 µg of
phytohemagglutinin (PHA; Sigma)/ml and 50 U of human interleukin 2/ml.
At the indicated times, the microplates were frozen and thawed once.
After centrifugation at 280 × g for 2 min, the supernatants
were collected and titrated by the method of 50% tissue culture
infective doses (TCID50) on a Vero cell monolayer. MV tag
and MV V showed similar increases in the number of
infectious units and reached 25,000 TCID50/ml at 5 days
postinfection (p.i.) (Fig. 1). However,
MV C reached a maximum production of 39 TCID50/ml at day 3 p.i. and then declined. Since no
differences in viral production of these MV mutants have been reported
when Vero cells are used (15, 19), a parallel experiment
using this cell line was performed. An MOI of 1 TCID50/cell
was used to infect PBMC in order to obtain an optimal level of virus
progeny, but this concentration of virus induced premature destruction
of the cell monolayer on Vero cells. Therefore, an MOI of 0.01 TCID50/cell was used to infect Vero cells. In agreement
with the previous reports, no difference in viral production was found
in Vero cells, and the increase in the number of infectious units was
similar no matter which virus was used (Fig. 1). Because of massive
destruction of the monolayer at day 4 p.i., the kinetics were
analyzed up to day 3. The difference observed for MV C
between PBMC and Vero cells was not related to the different MOIs used,
because the infection of PBMC with an MOI of 0.01 TCID50/cell recapitulated the results obtained with an MOI
of 1 TCID50/cell, although with a very low level of virus
progeny (data not shown). A specific block of the entry of MV
C particles into PBMC is unlikely because (i) the same
virus stock readily infected Vero cells and (ii) the C protein is not a
component of the mature virion (1). These data indicated
that the lack of C protein expression strongly impaired the infection
of human PBMC, whereas it had no major influence on the infection of
Vero cells.
View larger version (11K):
[in this window]
[in a new window]
|
FIG. 1.
Kinetics of infectious virus production by human PBMC
and Vero cells infected with MV tag (diamonds), MV C
(circles), or MV V (triangles). The activated PBMC and
Vero cells were infected at MOIs of 1 and 0.01, respectively.
|
|
Restricted virus protein and mRNA synthesis after MV
C infection in PBMC.
To determine whether the
differences observed in virus production were correlated with virus
protein synthesis, the cell surface expression of the H protein on
activated PBMC and on Vero cells was analyzed by flow cytometry at day
2 p.i. The immunofluorescence labelling procedure has been
described elsewhere (9). Infection of PBMC with MV
C resulted in 9% of cells expressing the H protein,
whereas infection with MV tag and MV V resulted in 31 and
43% of cells expressing the H protein, respectively (Fig.
2A). In contrast, 93, 94, and 99% of
Vero cells expressed H when infected with MV C, MV tag,
and MV V, respectively (Fig. 2A). Interestingly, compared
to MV tag infection, MV V infection resulted in a
consistent 5 to 10% increase in the numbers of H-expressing cells
among both PBMC and Vero cells, suggesting that in the absence of V
protein, MV may replicate more efficiently. Similar results were
obtained when F protein expression was measured (data not shown).
View larger version (13K):
[in this window]
[in a new window]
|
FIG. 2.
Cell surface expression of the H protein after infection
of human PBMC and Vero cells with MV tag, MV C, or MV
V at MOIs of 1 and 0.01, respectively. (A) Histogram
profile of H expression 2 days after mock infection (solid histograms)
or MV infection (open histograms). (B) Kinetics of H expression after
infection of PBMC with no virus (open squares), MV tag (solid
diamonds), MV C (solid circles), or MV V
(solid triangles).
|
|
To confirm the lower efficiency of virus protein expression in PBMC
infected with MV C
, the kinetics of H expression were
studied. Even after 7 days
of culture, fewer than 20% of PBMC were
found to express detectable
H at their surfaces after infection with MV
C
(Fig.
2B). In contrast, MV tag and MV V
infections resulted in H expression on 18 and 12% of cells,
respectively,
as early as 1 day p.i.; these levels increased to 58 and
70% at
5 days p.i.
The expression of the H and F proteins was also analyzed by
immunoblotting (Fig.
3). Briefly, the
infected cells were lysed
in 1% Nonidet P-40 buffer containing 150 mM
NaCl, 50 mM Tris-HCl
(pH 8.5), 5 mM EDTA, 10 mM NaF, and anti-proteases
(20 µM E64,
100 µM DCI, 100 µM phenanthroline; Boehringer
Mannheim and Sigma).
After a 15-min incubation at 4°C, lysates were
centrifuged for
15 min at 12,000 ×
g. Proteins were
separated by sodium dodecyl
sulfate-polyacrylamide gel electrophoresis
under reducing conditions
and transferred to polyvinylidene difluoride
membranes (Boehringer
Mannheim). Membranes were blocked with 5% nonfat
dried milk in
TBS-T (20 mM Tris [pH 7.6], 150 mM NaCl, 0.1% Tween
20) and incubated
for 1 h with specific antibodies in TBS-T
(monoclonal antibody
anti-H BH164 [
7] or polyclonal
anti-F cytoplasmic tail Pocono
[
3]). Immunoreactive
bands were visualized by using secondary
horseradish
peroxidase-conjugated antibodies (Promega) and enhanced
chemiluminescence (Pierce). The expression levels of H and F
glycoproteins
were almost identical in PBMC infected with MV tag and
PBMC infected
with MV V
. In contrast, the levels of these
proteins in PBMC infected with
MV C
were lower. Control
immunoblotting with anti-S6 kinase antibody
showed that comparable
amounts of protein were loaded in each
lane (Fig.
3).
View larger version (41K):
[in this window]
[in a new window]
|
FIG. 3.
Western blot analysis of the expression of H and F
proteins by human PBMC infected with MV tag, MV C, or MV
V at an MOI of 1 at day 3 p.i. S6K, S6 kinase.
|
|
Since the expression of the H and F glycoproteins was reduced both at
the cell surface (as measured by cytofluorometry) and
intracellularly
(as measured by Western blotting with whole-cell
extracts), we could
exclude any impairment of MV glycoprotein
maturation due to the lack of
C
protein.
Because of its high positive charge at physiological pH and its
colocalization with the nucleoprotein in infected cells (
1),
the C protein was proposed to interact with RNA and play a role
during
viral transcription and/or replication (
11). Therefore,
the
synthesis of MV N mRNA and MV genome RNA was evaluated in
PBMC infected
with MV tag or MV C
. By using the SV Total RNA Isolation
System kit (Promega), total
RNA was extracted from activated PBMC and
either left uninfected
or infected for 4 days with MV tag or MV
C
. MV N mRNA and MV genome RNA were specifically
quantified by
densitometry of a dot blot. After hybridization with
digoxigenin
(DIG)-labelled N riboprobes of negative and positive
polarities,
the dot blot was revealed with anti-DIG-alkaline
phosphatase conjugate
and CDP-Star substrate (Roche Diagnostic). These
probes were done
by using the DIG RNA labelling kit SP6/T7 (Roche
Diagnostic) from
the plasmid pGEM-N in which the N nucleotide sequence
825 to 1676
was cloned between the initiation sites of SP6 and T7
polymerase
(
5). A control DIG-labelled actin RNA probe
(Roche Diagnostic)
was used. The contribution of the antigenome to the
N mRNA signal
was found to be negligible when the negative-polarity
riboprobe
was used. In the absence of C protein, the amounts of MV
genome
RNA and N mRNA were reduced by 25 and 66%, respectively. Thus,
in PBMC, the MV C protein seemed to be required for optimal
transcription,
whereas it affected viral genome replication only
modestly.
Almost no virus progeny was recovered from MV C
-infected
human PBMC, and this correlated well with the low expression level
of
the viral proteins. Since the infection of the PBMC was performed
at a
high MOI of 1 TCID
50/cell, most, if not all, virus protein
expression was from the initial infectious virus input. Indeed,
when
the secondary cell-to-cell virus spreading was inhibited
by the
addition of a fusion tripeptide inhibitor,
Z-
D-Phe-
L-Phe-Gly,
2 h after
the infection (
17), no significant decrease was observed
in
the percentage of PBMC expressing H and F glycoproteins or
in their
expression levels, no matter which recombinant MV was
used (data not
shown).
The reductions in virus protein synthesis and virus progeny after MV
C
infection observed in human PBMC but not in Vero cells
suggest
that the C protein function might be restricted to certain cell
types. Restriction of the replication of Sendai V
recombinant virus in some, but not all, cell lines has also been
observed (
12). A role for certain accessory proteins might
then
be to compensate for a missing cellular function in some cells.
Importantly, PBMC are responsible for the MV spreading into the
lymphoid organs (
24). Therefore, our findings predict an
essential
role of the MV C protein for the virulence of MV in
humans.
Inhibitory effect of recombinant MV on the proliferative response
of PBMC.
The reduced replication of MV C in
activated PBMC led us to explore the role of the C protein in
MV-induced inhibition of PHA-stimulated PBMC proliferation. Infected
and mock-infected human PBMC were cultured in 0.2 ml (final volume)
(5 × 104 cells/well) in 96-well flat-bottom microwell
plates at 37°C. After 48 h of incubation, cells were pulsed with
[3H]thymidine for 12 h and then harvested on glass
fiber filters. The radioactivity was counted in a liquid scintillation
beta counter. Surprisingly, MV C infection was as
inhibitory as parental MV tag infection (Fig. 4), leading to an average of 50%
inhibition of thymidine uptake in three independent experiments. MV
V was consistently more efficient in inhibiting PBMC
proliferation, leading to an average of 65% inhibition of
proliferation. Thus, the C and V proteins are dispensable for the
MV-induced inhibition of the PBMC proliferative response. These results
further indicate that proliferation inhibition by MV does not require
maximum virus replication. In support of this are the observations that
even a small number of MV-infected PBMC can inhibit the proliferation of uninfected PBMC (18).
View larger version (38K):
[in this window]
[in a new window]
|
FIG. 4.
MV-induced inhibition of PBMC proliferation. PBMC were
stimulated with PHA and interleukin 2 and infected with the indicated
virus at an MOI of 1. The proliferation level was determined by
[3H]thymidine incorporation, and results are expressed as
counts per minute (means of triplicates ± standard deviations).
|
|
In conclusion, the infection of human PBMC with recombinant MV
C
resulted in impaired synthesis of viral proteins and
infectious
virus production, indicating an important role for C in the
natural
host cells. In contrast, and as previously reported, no
differences
were observed in Vero cells. Further studies on the role of
the
C protein would allow us to determine whether any cellular
components
can compensate for the function of C in Vero cells, and
whether
the C protein plays a crucial role during an in vivo infection,
as recently suggested by the reduced replication of MV C
in human thymic xenografts (
22). The V protein does not seem
to play a major role in MV replication in PBMC. However, this
does not
preclude the importance of V in the in vivo replication
of MV, as
illustrated by the reduced replication of MV V
observed
in human thymic xenografts (
22) and in cotton rats
(
21).
| |
ACKNOWLEDGMENTS |
C.E. and S.M. contributed equally to this work.
We acknowledge R. Cattaneo for the kind gifts of anti-F rabbit antisera
and pGEM-N plasmid and Dale Christiansen for help in writing the manuscript.
This work was partially supported by a grant from the Ministère
de l'Enseignement Supérieur et de la Recherche.
| |
FOOTNOTES |
*
Corresponding author. Mailing address: Immunité
et Infections Virales, IVMC, CNRS-UCBL, UMR 5537, 69372 Lyon Cedex 08, France. Phone: 33 4 78 77 86 18. Fax: 33 4 78 77 87 54. E-mail:
gerlier{at}laennec.univ-lyon1.fr.
| |
REFERENCES |
| 1.
|
Bellini, W. J.,
G. Englund,
S. Rozenblatt,
H. Arnheiter, and C. D. Richardson.
1985.
Measles virus P gene codes for two proteins.
J. Virol.
53:908-919[Abstract/Free Full Text].
|
| 2.
|
Bellini, W. J.,
J. S. Rota, and P. A. Rota.
1994.
Virology of measles virus.
J. Infect. Dis.
170:S15-S23.
|
| 3.
|
Cathomen, T.,
H. Y. Naim, and R. Cattaneo.
1998.
Measles viruses with altered envelope protein cytoplasmic tails gain cell fusion competence.
J. Virol.
72:1224-1234[Abstract/Free Full Text].
|
| 4.
|
Cattaneo, R.,
K. Kaelin,
K. Baczko, and M. A. Billeter.
1989.
Measles virus editing provides an additional cysteine-rich protein.
Cell
56:759-764[Medline].
|
| 5.
|
Cattaneo, R.,
G. Rebman,
A. Schmid,
K. Baczko,
V. ter Meulen, and M. Billeter.
1987.
Altered transcription of a defective measles virus genome derived from a diseased human brain.
EMBO J.
6:681-688[Medline].
|
| 6.
|
Delenda, C.,
S. Hausmann,
D. Garcin, and D. Kolakofsky.
1997.
Normal cellular replication of Sendai virus without the trans-frame, nonstructural V protein.
Virology
228:55-62[Medline].
|
| 7.
|
Fournier, P.,
N. H. Brons,
G. A. Berbers,
K. H. Wiesmuller,
B. T. Fleckenstein,
F. Schneider,
G. Jung, and C. P. Muller.
1997.
Antibodies to a new linear site at the topographical or functional interface between the haemagglutinin and fusion proteins protect against measles encephalitis.
J. Gen. Virol.
78:1295-1302[Abstract].
|
| 8.
|
Garcin, D.,
M. Itoh, and D. Kolakofsky.
1997.
A point mutation in the Sendai virus accessory C proteins attenuates virulence for mice, but not virus growth in cell culture.
Virology
238:424-431[Medline].
|
| 9.
|
Gerlier, D.,
B. Loveland,
G. Varior-Krishnan,
B. Thorley,
I. F. C. Mckenzie, and C. Rabourdin-Combe.
1994.
Measles virus receptor properties are shared by several CD46 isoforms differing in extracellular regions and cytoplasmic tails.
J. Gen. Virol.
75:2163-2171[Abstract/Free Full Text].
|
| 10.
|
Griffin, D. E.
1995.
Immune responses during measles virus infection.
Curr. Top. Microbiol. Immunol.
191:117-134[Medline].
|
| 11.
|
Horikami, S. M., and S. A. Moyer.
1995.
Structure, transcription and replication of measles virus.
Curr. Top. Microbiol. Immunol.
191:35-50[Medline].
|
| 12.
|
Kato, A.,
K. Kiyotani,
Y. Sakai,
T. Yoshida, and Y. Nagai.
1997.
The paramyxovirus, Sendai virus, V protein encodes a luxury function required for viral pathogenesis.
EMBO J.
16:578-587[Medline].
|
| 13.
|
Kato, A.,
K. Kiyotani,
Y. Sakai,
T. Yoshida,
T. Shioda, and Y. Nagai.
1997.
Importance of the cysteine-rich carboxyl-terminal half of V protein for Sendai virus pathogenesis.
J. Virol.
71:7266-7272[Abstract].
|
| 14.
|
Liston, P., and D. J. Briedis.
1995.
Ribosomal frameshifting during translation of measles virus P protein mRNA is capable of directing synthesis of a unique protein.
J. Virol.
69:6742-6750[Abstract].
|
| 15.
|
Radecke, F., and M. A. Billeter.
1996.
The nonstructural C protein is not essential for multiplication of Edmonston B strain measles virus in cultured cells.
Virology
217:418-421[Medline].
|
| 16.
|
Radecke, F.,
P. Spielhofer,
H. Schneider,
K. Kaelin,
M. Huber,
C. Dotsch,
G. Christiansen, and M. A. Billeter.
1995.
Rescue of measles viruses from cloned DNA.
EMBO J.
14:5773-5784[Medline].
|
| 17.
|
Richardson, C. D.,
A. Scheid, and P. W. Choppin.
1980.
Specific inhibition of paramyxovirus and myxovirus replication by oligopeptides with amino acid sequences similar to those at the N termini of the F1 or HA2 viral polypeptides.
Virology
105:205-222[Medline].
|
| 18.
|
Schlender, J.,
J. J. Schnorr,
P. Spielhofer,
T. Cathomen,
R. Cattaneo,
M. A. Billeter,
V. ter Meulen, and S. Schneider-Schaulies.
1996.
Interaction of measles virus glycoproteins with the surface of uninfected peripheral blood lymphocytes induces immunosuppression in vitro.
Proc. Natl. Acad. Sci. USA
93:13194-13199[Abstract/Free Full Text].
|
| 19.
|
Schneider, H.,
K. Kaelin, and M. A. Billeter.
1997.
Recombinant measles viruses defective for RNA editing and V protein synthesis are viable in cultured cells.
Virology
227:314-322[Medline].
|
| 20.
|
Sullivan, J. L.,
D. W. Barry,
P. Albrecht, and S. J. Lucas.
1975.
Inhibition of lymphocyte stimulation by measles virus.
J. Immunol.
114:1458-1461[Abstract/Free Full Text].
|
| 21.
|
Tober, C.,
M. Seufert,
H. Schneider,
M. A. Billeter,
I. C. D. Johnston,
S. Niewesk,
V. ter Meulen, and S. Schneider-Schaulies.
1998.
Expression of measles virus V protein is associated with pathogenicity and control of viral RNA synthesis.
J. Virol.
72:8124-8132[Abstract/Free Full Text].
|
| 22.
|
Valsamakis, A.,
H. Schneider,
P. G. Auwaerter,
H. Kaneshima,
M. Billeter, and D. E. Griffin.
1998.
Recombinant measles virus with mutations in the C, V or F gene have altered growth phenotypes in vivo.
J. Virol.
72:7754-7761[Abstract/Free Full Text].
|
| 23.
|
Wardrop, E. A., and D. J. Briedis.
1991.
Characterization of V protein in measles virus-infected cells.
J. Virol.
65:3421-3428[Abstract/Free Full Text].
|
| 24.
|
White, R. G., and J. F. Boyd.
1973.
The effect of measles on the thymus and other lymphoid tissues.
Clin. Exp. Immunol.
13:343-357[Medline].
|
Journal of Virology, February 1999, p. 1695-1698, Vol. 73, No. 2
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Lo, M. K., Harcourt, B. H., Mungall, B. A., Tamin, A., Peeples, M. E., Bellini, W. J., Rota, P. A.
(2009). Determination of the henipavirus phosphoprotein gene mRNA editing frequencies and detection of the C, V and W proteins of Nipah virus in virus-infected cells. J. Gen. Virol.
90: 398-404
[Abstract]
[Full Text]
-
Toth, A. M., Devaux, P., Cattaneo, R., Samuel, C. E.
(2009). Protein Kinase PKR Mediates the Apoptosis Induction and Growth Restriction Phenotypes of C Protein-Deficient Measles Virus. J. Virol.
83: 961-968
[Abstract]
[Full Text]
-
Nakatsu, Y., Takeda, M., Ohno, S., Koga, R., Yanagi, Y.
(2006). Translational Inhibition and Increased Interferon Induction in Cells Infected with C Protein-Deficient Measles Virus. J. Virol.
80: 11861-11867
[Abstract]
[Full Text]
-
Yanagi, Y., Takeda, M., Ohno, S.
(2006). Measles virus: cellular receptors, tropism and pathogenesis.. J. Gen. Virol.
87: 2767-2779
[Abstract]
[Full Text]
-
Takeuchi, K., Takeda, M., Miyajima, N., Ami, Y., Nagata, N., Suzaki, Y., Shahnewaz, J., Kadota, S.-i., Nagata, K.
(2005). Stringent Requirement for the C Protein of Wild-Type Measles Virus for Growth both In Vitro and in Macaques. J. Virol.
79: 7838-7844
[Abstract]
[Full Text]
-
Malur, A. G., Chattopadhyay, S., Maitra, R. K., Banerjee, A. K.
(2005). Inhibition of STAT 1 Phosphorylation by Human Parainfluenza Virus Type 3 C Protein. J. Virol.
79: 7877-7882
[Abstract]
[Full Text]
-
Baron, M. D., Banyard, A. C., Parida, S., Barrett, T.
(2005). The Plowright vaccine strain of Rinderpest virus has attenuating mutations in most genes. J. Gen. Virol.
86: 1093-1101
[Abstract]
[Full Text]
-
Devaux, P., Cattaneo, R.
(2004). Measles Virus Phosphoprotein Gene Products: Conformational Flexibility of the P/V Protein Amino-Terminal Domain and C Protein Infectivity Factor Function. J. Virol.
78: 11632-11640
[Abstract]
[Full Text]
-
Ohno, S., Ono, N., Takeda, M., Takeuchi, K., Yanagi, Y.
(2004). Dissection of measles virus V protein in relation to its ability to block alpha/beta interferon signal transduction. J. Gen. Virol.
85: 2991-2999
[Abstract]
[Full Text]
-
Laine, D., Trescol-Biemont, M.-C., Longhi, S., Libeau, G., Marie, J. C., Vidalain, P.-O., Azocar, O., Diallo, A., Canard, B., Rabourdin-Combe, C., Valentin, H.
(2003). Measles Virus (MV) Nucleoprotein Binds to a Novel Cell Surface Receptor Distinct from Fc{gamma}RII via Its C-Terminal Domain: Role in MV-Induced Immunosuppression. J. Virol.
77: 11332-11346
[Abstract]
[Full Text]
-
Yokosawa, N., Yokota, S.-i., Kubota, T., Fujii, N.
(2002). C-Terminal Region of STAT-1{alpha} Is Not Necessary for Its Ubiquitination and Degradation Caused by Mumps Virus V Protein. J. Virol.
76: 12683-12690
[Abstract]
[Full Text]
-
Neumann, G., Whitt, M. A., Kawaoka, Y.
(2002). A decade after the generation of a negative-sense RNA virus from cloned cDNA - what have we learned?. J. Gen. Virol.
83: 2635-2662
[Abstract]
[Full Text]
-
Bankamp, B., Kearney, S. P., Liu, X., Bellini, W. J., Rota, P. A.
(2002). Activity of Polymerase Proteins of Vaccine and Wild-Type Measles Virus Strains in a Minigenome Replication Assay. J. Virol.
76: 7073-7081
[Abstract]
[Full Text]
-
Kato, A., Ohnishi, Y., Hishiyama, M., Kohase, M., Saito, S., Tashiro, M., Nagai, Y.
(2002). The Amino-Terminal Half of Sendai Virus C Protein Is Not Responsible for either Counteracting the Antiviral Action of Interferons or Down-Regulating Viral RNA Synthesis. J. Virol.
76: 7114-7124
[Abstract]
[Full Text]
-
Vincent, S., Tigaud, I., Schneider, H., Buchholz, C. J., Yanagi, Y., Gerlier, D.
(2002). Restriction of Measles Virus RNA Synthesis by a Mouse Host Cell Line: trans-Complementation by Polymerase Components or a Human Cellular Factor(s). J. Virol.
76: 6121-6130
[Abstract]
[Full Text]
-
Ohgimoto, S., Ohgimoto, K., Niewiesk, S., Klagge, I. M., Pfeuffer, J., Johnston, I. C. D., Schneider-Schaulies, J., Weidmann, A., ter Meulen, V., Schneider-Schaulies, S.
(2001). The haemagglutinin protein is an important determinant of measles virus tropism for dendritic cells in vitro. J. Gen. Virol.
82: 1835-1844
[Abstract]
[Full Text]
-
Parks, C. L., Lerch, R. A., Walpita, P., Wang, H.-P., Sidhu, M. S., Udem, S. A.
(2001). Comparison of Predicted Amino Acid Sequences of Measles Virus Strains in the Edmonston Vaccine Lineage. J. Virol.
75: 910-920
[Abstract]
[Full Text]
-
Parks, C. L., Lerch, R. A., Walpita, P., Wang, H.-P., Sidhu, M. S., Udem, S. A.
(2001). Analysis of the Noncoding Regions of Measles Virus Strains in the Edmonston Vaccine Lineage. J. Virol.
75: 921-933
[Abstract]
[Full Text]
-
Takeda, M., Takeuchi, K., Miyajima, N., Kobune, F., Ami, Y., Nagata, N., Suzaki, Y., Nagai, Y., Tashiro, M.
(2000). Recovery of Pathogenic Measles Virus from Cloned cDNA. J. Virol.
74: 6643-6647
[Abstract]
[Full Text]
-
Baron, M. D., Barrett, T.
(2000). Rinderpest Viruses Lacking the C and V Proteins Show Specific Defects in Growth and Transcription of Viral RNAs. J. Virol.
74: 2603-2611
[Abstract]
[Full Text]
-
Mrkic, B., Odermatt, B., Klein, M. A., Billeter, M. A., Pavlovic, J., Cattaneo, R.
(2000). Lymphatic Dissemination and Comparative Pathology of Recombinant Measles Viruses in Genetically Modified Mice. J. Virol.
74: 1364-1372
[Abstract]
[Full Text]
-
Vialat, P., Billecocq, A., Kohl, A., Bouloy, M.
(2000). The S Segment of Rift Valley Fever Phlebovirus (Bunyaviridae) Carries Determinants for Attenuation and Virulence in Mice. J. Virol.
74: 1538-1543
[Abstract]
[Full Text]
-
Jin, H., Cheng, X., Zhou, H. Z. Y., Li, S., Seddiqui, A.
(2000). Respiratory Syncytial Virus That Lacks Open Reading Frame 2 of the M2 Gene (M2-2) Has Altered Growth Characteristics and Is Attenuated in Rodents. J. Virol.
74: 74-82
[Abstract]
[Full Text]
-
Duprex, W. P., McQuaid, S., Hangartner, L., Billeter, M. A., Rima, B. K.
(1999). Observation of Measles Virus Cell-to-Cell Spread in Astrocytoma Cells by Using a Green Fluorescent Protein-Expressing Recombinant Virus. J. Virol.
73: 9568-9575
[Abstract]
[Full Text]
Top
Abstract
Text
