Previous Article | Next Article 
Journal of Virology, January 2000, p. 987-991, Vol. 74, No. 2
0022-538X/00/$04.00+0
Genetic Determinants of Altered Virulence of
Taiwanese Foot-and-Mouth Disease Virus
Clayton W.
Beard
and
Peter W.
Mason*
Plum Island Animal Disease Center,
Agricultural Research Service, U.S. Department of Agriculture,
Greenport, New York
Received 17 June 1999/Accepted 6 October 1999
 |
ABSTRACT |
In 1997, a devastating outbreak of foot-and-mouth disease (FMD) in
Taiwan was caused by a serotype O virus (referred to here as OTai) with
atypical virulence. It produced high morbidity and mortality in swine
but did not affect cattle. We have defined the genetic basis of the
species specificity of OTai by evaluating the properties of genetically
engineered chimeric viruses created from OTai and a bovine-virulent FMD
virus. These studies have shown that an altered nonstructural protein,
3A, is a primary determinant of restricted growth on bovine cells in
vitro and significantly contributes to bovine attenuation of OTai in vivo.
| |
TEXT |
Foot-and-mouth disease (FMD) is an
extremely contagious viral disease of cloven-hoofed animals, most
notably cattle, pigs, and sheep. FMD is characterized by fever,
vesicular lesions, and erosions of the epithelium of the mouth, tongue,
nares, muzzle, feet, and teats (22). Despite recent success
in controlling the disease in Europe and portions of South America, FMD
remains one of the most important infectious diseases of farm animals due to the impact an outbreak can have on trade in animals and animal
products (13). Foot-and-mouth disease virus (FMDV), a positive-stranded RNA virus, is the type member of the
Aphthovirus genus of the family Picornaviridae, a
family which includes many important pathogens of humans and domestic
animals. There are seven recognized serotypes of FMDV, but new subtypes
with altered antigenic properties frequently emerge due to the
well-characterized genetic instability of the virus (5).
Recent FMD outbreak in Taiwan.
In 1997, a devastating and
unusual outbreak of FMD, characterized by disease in swine but not in
cattle, occurred in Taiwan. The outbreak, which was caused by a
serotype O virus (OTai) with an atypical porcinophilic phenotype
(6), rapidly developed into a massive epizootic,
resulting in cessation of export of all pork products from the country.
This outbreak devastated the Taiwanese swine industry (approximately 4 million swine were destroyed) and had a severe impact on the national
economy due to costs of control and trade restrictions (estimated at
over 6 billion U.S. dollars). During the course of this outbreak, no
cattle were reported to have been affected, and virus isolated from
infected swine was unable to infect bovine thyroid cells in vitro or to
cause typical disease in bovines following intradermal inoculation in the tongue (6).
Genomic regions responsible for host range specificity in
vitro.
To define the genetic components of OTai responsible for
its porcinophilic phenotype, we have generated and evaluated
recombinant viruses with sequences of OTai substituted for sequences of
an FMDV strain of high virulence in bovines (25). The
engineered chimeric viruses produced for these studies are derived from
in vitro-generated RNA transcripts of genome-length cDNAs by using standard techniques (17, 23). Specifically, all chimeric
viruses used in these studies were generated by high-efficiency
transfection of BHK cells (17), and experiments were
performed with low-passage (less than five) stocks of virus produced by
high-multiplicity infection of BHK cell cultures. Figure
1 shows schematic diagrams of the genomes
of selected chimeric viruses along with photographs of plaques formed
by these viruses in monolayer cultures of BHK or bovine kidney (BK)
cells. All viruses that formed plaques on BHK cells also formed plaques
on both IB-RS-2 cells (a porcine kidney cell line [6])
and porcine kidney cells (data not shown).
View larger version (46K):
[in this window]
[in a new window]
|
FIG. 1.
Structures of genetically engineered virus genomes and
plaque assays of viruses containing these genomes on BHK and BK cells.
Linear representations of the 8.4-kb chimeric genomes show the source
of their sequences as indicated in the key at the bottom of the figure.
Genetic elements: S, small fragment of the genome; Cn, poly(C) tract;
IRES, internal ribosome entry site; L, leader proteinase-encoding
region; P1/2A, capsid precursor coding region; P2 and P3, nonstructural
protein precursor-encoding regions; An, poly(A) tract. Viral RNA
recovered from porcine lesions was reverse transcribed, and specific
portions of the resulting cDNA were amplified by PCR amplification with
a high-fidelity polymerase (27). The segment of the genome
between the poly(C) tract and the 3' poly(A) tract was amplified and
molecularly cloned in E. coli in three separate portions.
The portion extending from the poly(C) tract to the beginning of the
coding sequence for 1B was amplified with an oligonucleotide containing
an AvrII site found at the border of the poly(C) tract of
the serotype A12 genome followed by 28 nucleotides of the adjacent
sequence (23) and an antisense oligonucleotide corresponding
to codons 13 to 22 of protein 1B of OTai, containing mutations in
codons 13 to 15, that produce an SspI site without altering
the coding capacity of the sequence. The portion extending from 1B to
2A was amplified by using an oligonucleotide corresponding to codons 13 to 21 of protein 1B of O1 Campos (containing the same mutations needed
to produce an SspI site) and an antisense oligonucleotide
corresponding to codons 12 to 18 of 2A (containing mutations to produce
an XmaI site in codons 17 and 18, without altering their
coding capacity). The final portion of the genome was amplified by
using an oligonucleotide corresponding to codons 17 and 18 of 2A (with
the XmaI site described above) and the first six codons of
OTai 2B and an oligo(T) oligonucleotide containing 15 T's and a
NotI site (23). These fragments were assembled
into serotype A12 or serotype A12/OTai chimeric cDNAs and used to
generate viruses (see text) (17, 23). Chimeras with
exchanged 3A sequences were created by utilizing existing
NcoI sites at codons 215 to 217 in 2C and 110 to 112 of 3D
shared by OTai and A12 or by introducing EcoRI and
EcoRV sites (12) into OTai sequences at codons 24 and 25 of 3A and 98 and 99 of 3C, respectively, in a manner that
preserved the coding capacity and permitted in-frame fusion to existing
sites in A12 cDNA. Monolayer cultures of BHK and BK cells were infected
side-by-side with 10-fold dilutions of virus stocks prepared from each
chimeric genome and stained 2 days after infection to reveal plaques
(23). The paired BHK and BK monolayers selected for display
on the right side of this figure corresponded to those in which the
virus dilutions produced 10 to 50 plaques on BHK cells.
|
|
The virus whose structure is shown first in Fig.
1, vOTaiCn-An, is
derived from a full-length cDNA containing the entire OTai
protein-encoding sequence. This chimera contains the A12 S fragment
and
poly(C) tract found in all of the viruses used in this study
(
23), with the remainder of the genome [poly(C) tract to
poly(A)
tail] derived by PCR amplification of cDNA reverse transcribed
from OTai virus RNA extracted from lesions of swine infected with
a
field isolate of OTai (see legend to Fig.
1). As expected, vOTaiCn-An
displays the growth restriction of field isolates of OTai on bovine
cells (
6). Immunostaining of BK cells infected with
vOTaiCn-An
showed that this virus could establish a limited
infection in
bovine cells, as indicated by few FMDV antigen-positive
cells
and no spread of infection to surrounding cells (data not shown).
The virus whose structure is shown second in Fig.
1, vO1CamP1,
is a
chimeric virus previously generated (referred to as vCRM8
in references
1,
20, and
25) by inserting the
capsid-encoding
region (proteins 1A, 1B, 1C, and 1D) of serotype O1
Campos (from
a 1958 bovine isolate from Brazil) in the genetic
background of
a high-passage serotype A12 virus (from a 1932 bovine
isolate
from the United Kingdom) (
23,
25). vO1CamP1 displays
a high
level of virulence in cattle (
25) and swine
(
1) and efficiently
forms plaques in BHK and BK cell
monolayers (Fig.
1). The virus
whose structure is shown after vO1CamP1
in Fig.
1, vOTaiP1, encodes
the surface-exposed capsid proteins (1B,
1C, and 1D) of OTai in
the background of the serotype A12 virus.
Interestingly, this
virus, whose capsid differs significantly from the
South American
O1 capsid (Table
1),
displays plaquing ability similar to that
of vO1CamP1 on both BHK and
BK cells (Fig.
1). These findings
indicate that the basis of growth
restriction in BK cells in vitro
was not due to alterations in the
capsid, although our previous
work has shown a profound influence of
FMDV capsid sequences on
receptor specificity and tropism in cell
culture and virulence
in animals (
20,
25). Furthermore,
results obtained by evaluation
of other chimeras failed to show a role
for either the OTai Leader
proteinase coding region (known to
contribute to virus virulence
in bovines [
2,
18]) or
the OTai translation initiation site
(the internal ribosome entry site
region, well known for its role
in determining the virulence of the
related picornavirus that
causes poliomyelitis [reviewed in reference
28]) in restricting
replication in bovine cell
cultures (results not shown).
View this table:
[in this window]
[in a new window]
|
TABLE 1.
Summary of differences in predicted amino acid sequences
between the capsid-encoding regions of O1 Campos and OTai
|
|
To further map the basis of the altered host range of OTai, a series of
viruses were generated to dissect the nonstructural
protein-encoding
regions (P2 and P3). Sequence data obtained during
the construction of
these chimeras revealed a significant difference
among the 3A coding
regions of the OTai, A12, and O1 Kaufbeuren
(O1K) viruses (Table
2). The comparisons in Table
2 show that
the dramatic differences in the 3A coding regions of the two type
O
genomes stand in sharp contrast to the modest differences detected
between coding regions for 2B, 2C, 3B, 3C, and 3D between these
viruses, which are similar to the differences seen between the
P2 and
P3 coding regions of O1K and the A12 virus.
View this table:
[in this window]
[in a new window]
|
TABLE 2.
Comparison of differences between nonstructural
protein-encoding segments of the FMDV genomes of OTai, O1K, and A12
|
|
To test the importance of the 3A region in the bovine growth
restriction of OTai, three additional chimeras, shown at the
bottom of
Fig.
1, were constructed. These three viruses contained
either the
entire A12 3A coding region or the mutated portion
of 3A of OTai (see
below), along with some additional regions.
In all three chimeras shown
at the bottom of Fig.
1, the exchanged
regions extend beyond the 3A
coding region, and in two of the
cases, the first 24 codons of the OTai
3A coding region were not
included in the chimeras (the amino acids
encoded by A12 and OTai
are identical in this 24-codon region) (see
Fig.
2). However,
in the extensions beyond the borders of 3A, the
substituted codons
correspond to a small number of well-spaced single
amino acid
substitutions that are largely conservative in nature (in
the
NcoI fragment exchanged to form virus vOTaiCn-An/A123A-C
[Fig.
1], a total of 3 substitutions in 2C, 5 substitutions in 3BBB,
12 changes in 3C, and 5 changes in 3D were incorporated along
with 40 changes clustered in the latter half of 3A; in the
EcoRI-
EcoRV
fragment exchanged to construct
vO1CamP1/Tai3A or vOTaiP1/OTai3A
[see Fig.
1], 5 changes in 3BBB and
1 change in 3C were incorporated
in addition to the 40 changes
clustered in the latter half of
3A). Thus, the only significant changes
between the last three
viruses in Fig.
1 and their corresponding
parents are in the 3A
coding region. A comparison of the abilities of
these three viruses
to form plaques on BK cells revealed that
substitution of the
OTai 3A coding region into vO1CamP1 or vOTaiP1
produced viruses
that were unable to form plaques on BK cells, whereas
the substitution
of the A12 3A into O1TaiCn-An produced a virus capable
of forming
plaques on these cells (Fig.
1). The plaques formed on BK
cells
by this latter virus were smaller than those produced by
vOTaiP1
and vO1CamP1, suggesting that other regions of the genome
contribute
to OTai growth restriction on BK cells. Taken together, the
data
in Fig.
1 demonstrate that the OTai 3A coding region is the
primary
determinant of the growth restriction of OTai on BK
cells.
As pointed out in Table
2, sequence analyses of the genome of OTai
revealed a high degree of identity to O1 and A12, except
for the 3A
coding region. The divergence in 3A sequences among
these viruses
reflects two dramatic differences in the OTai 3A
coding region. The
first is a 10-amino-acid deletion corresponding
to codons 93 through
102 of the European and South American 3A
coding regions, and the
second is a large number of mutation located
between codons 128 and 147 of the European and South American
3A coding regions. Interestingly,
the deletion in the OTai 3A
is similar to a deletion found in
egg-passaged derivatives of
O1 Campos (Fig.
2) and C3 Resende (
9). Both of
these egg-passaged
viruses, which were developed and used as
live-attenuated FMD
vaccines in bovines in South America (
21,
26), exhibited a
greatly reduced ability to form plaques on BK
cells, and the C3
derivative was reported to have maintained its
virulence in swine
(
26). Evaluation of selected other 3A
sequences (C3 Argentina,
1985 (
7); SAT-2, Kenya, 1957 [J. W. I. Newman, A. M. Q. King,
and S. Ortlep,
personal communication]; and sequences obtained
from PCR-amplified
cDNAs of several other serotypes or subtypes
of FMDV [Asia1, Lebanon,
1983; O11, Indonesia, 1962]) showed that
none of these isolates
contained the deleted or mutated segments
identified in OTai.
View larger version (15K):
[in this window]
[in a new window]
|
FIG. 2.
Alignment of the deduced 3A amino acid sequences (shown
in single-letter code) of OTai, O1 Campos (9), A12
(24), and an egg-adapted O1 Campos (O1C-O/E) (9)
reveal significant differences among their C-terminal halves (a period
indicates identity to O1 Campos; a dash indicates a deletion). The
hydrophobic domain located at residues 61 to 76 (underlined) is thought
to function in membrane binding (29).
|
|
Genomic regions responsible for host range specificity in
vivo.
In vivo studies were conducted to establish the role of OTai
3A as a determinant of bovine virulence. vO1CamP1, which encodes the
typical, full-length 3A of serotype A12, has been shown in previous
studies to very efficiently cause vesicle formation on bovine tongues
following intradermal inoculation, with a 50% infectious dose of 5 to
50 PFU (25). Furthermore, the animals inoculated with
vO1CamP1 developed a systemic infection (25). A similar intradermal inoculation study performed with vOTaiCn-An in bovine 07 showed a significantly different outcome (Fig.
3A). In this case, lesions were detected
only at doses of 750,000 and 75,000 PFU, and the quality of the lesions
was significantly different than that observed with vO1CamP1.
Specifically, the lesions caused by the high doses of vOTaiCn-An did
not progress into sores denuded of epidermis, which were characteristic
of the vesicles formed with all inoculations of over 50 PFU of vO1CamP1
(or other cattle-virulent FMDV). Moreover, animal 07 did not display
lameness or vesicles on any feet during the 3-week observation period
following inoculation. Thus, our results with the genetically
engineered form of OTai are consistent with those obtained with the
field isolate (6).
View larger version (54K):
[in this window]
[in a new window]
|
FIG. 3.
Vesicle-forming ability of chimeric viruses in bovine
tongues. Bovines were sedated by intramuscular injection of xylazine at
22 mg/100 kg (body weight). The tongue was extended from the oral
cavity, washed with warm water, and given five 0.05-ml intradermal
inoculations of each virus dilution tested with a 22-gauge needle.
Segments of each panel correspond to photographs taken at 48 h
postinoculation of sections of the dorsal surface of the tongue given
five inoculations of the indicated number of PFU. (A to C) Bovine 07, 08, and 210 were inoculated with dilutions of the indicated viruses;
(D) bovine 101 was given two different dilutions of the four indicated
viruses.
|
|
Inoculation of bovine 08 with vO1TaiCn-An/A123A-C demonstrated that the
addition of the full-length, wild-type form of 3A
to this OTai
derivative produced a bovine-virulent virus (Fig.
3B). Forty-eight
hours after tongue inoculation with this virus,
vesicles were detected
at all doses greater than 6 PFU, showing
that this virus was highly
efficient in establishing infectious
foci in the epidermis of the
tongue (Fig.
3B). Interestingly,
bovine 08 did not display other signs
of systemic disease, including
pedal lesions or lameness, over the
3-week observation
period.
Addition of the OTai 3A coding sequence to vO1CamP1 was capable of
attenuating the infection caused by this virus. Bovine
210 was
inoculated with graded dilutions of vO1CamP1/OTai3A and
observed for 3 weeks. At 48 h, lesions were detected at the 260-PFU
dose, but
these lesions consisted of white swollen vesicles rather
than the
severe erosions detected with vO1CamP1 and vO1TaiCn-An/A123A-C
(Fig.
3C). However, the following day, erosions appeared (although
only at
doses greater than 260 PFU), and this animal showed a
systemic disease,
characterized by spread of the infection to
the feet. Infection of a
second bovine with dilutions of vO1CamP1/OTai3A
produced similar signs
of disease (results not
shown).
To confirm that our observations were not significantly influenced by
individual responses of animals to inoculation, a single
bovine was
inoculated with two doses each of four different viruses.
Bovine 101 was inoculated with vO1CamP1, vO1CamP1/OTai3A, vOTaiP1,
and
vOTaiP1/OTai3A (Fig.
3D) at doses of 40,000 or 40 PFU. Both
vO1CamP1
and vOTaiP1 were able to cause severe lesions at high
and low doses
(Fig.
3D). vO1CamP1/OTai3A was able to cause swelling
at the high dose,
but no lesions were detected at the low dose.
vOTaiP1/OTai3A was unable
to cause signs of infection at either
dose (Fig.
3D). Taken together,
these in vivo data demonstrate
that the mutated 3A coding region of
OTai plays a major role in
the attenuation of this virus in
bovines.
Although FMDV can be distinguished from other members of the
Picornaviridae by a much longer 3A protein (153 amino acids
versus
87 for poliovirus), all picornavirus 3A proteins contain a 15-
to 20-amino-acid hydrophobic domain approximately 60 to 80 residues
from their N termini that is thought to function in binding the
viral
RNA replication machinery to cellular membranes (
29).
Furthermore, the interaction of 3A with cellular membranes has
been
shown to cause a cytopathic effect, prevent surface expression
of
proteins, and to inhibit protein secretion from 3A-expressing
cells (
3,
4). Thus, changes in the interaction of 3A
with
the host cell could affect the outcome of infection by directly
altering RNA replication or by altering the ability of the cell
or the
host to mount a response to infection at the level of cytokine
secretion or display of viral antigens in the context of the major
histocompatibility complex. In the case of hepatitis A virus,
changes
in 3A have been documented during adaptation to cell culture
(
10,
11,
15,
19), and for poliovirus there is molecular
genetic
evidence that changes in 3A alter host range in vitro
(
14).
The activities of 3A in virus-infected cells, and their implication in
alteration of host range of other picornaviruses, support
a role for
OTai 3A in the altered virulence of OTai. Moreover,
the changes we have
detected in OTai, including a deletion similar
to those previously
reported for egg-adapted FMDVs (
9), suggest
that under some
circumstances altered 3A genes could have a selective
advantage.
Determining if these changes contribute to the high
level of virulence
of OTai in swine, and discovering the time
of appearance of these
changes in field isolates of FMDV, will
contribute to our understanding
of how a bovine-attenuated FMDV
emerged to cause this recent
devastating outbreak in
swine.
| |
ACKNOWLEDGMENTS |
A portion of this work was supported by a grant from the National
Pork Producers Council (no. 1998/48).
We thank K. Beard for assisting in sequence data collection and
analyses and D. Gregg, Foreign Animal Disease Diagnostic Laboratory, APHIS, USDA, PIADC, for supplying vesicular fluid obtained from a swine
inoculated with OTai.
| |
FOOTNOTES |
*
Corresponding author. Mailing address: Plum Island
Animal Disease Center, USDA, ARS, P.O. Box 848, Greenport, NY 11944. Phone: (631) 323-3177. Fax: (631) 323-2507. E-mail:
petermas{at}asrr.arsusda.gov.
Present address: Maxygen Inc., Redwood, CA 94063.
| |
REFERENCES |
| 1.
|
Almeida, M. R.,
E. Rieder,
J. Chinsangaram,
G. Ward,
C. Beard,
M. J. Grubman, and P. W. Mason.
1998.
Construction and evaluation of an attenuated vaccine for foot-and-mouth disease: difficulty adapting the leader proteinase-deleted strategy to the serotype O1 virus.
Virus Res.
55:49-60[CrossRef][Medline].
|
| 2.
|
Brown, C. C.,
M. E. Piccone,
P. W. Mason,
T. S. McKenna, and M. J. Grubman.
1996.
Pathogenesis of wild-type and leaderless foot-and-mouth disease virus in cattle.
J. Virol.
70:5638-5641[Abstract/Free Full Text].
|
| 3.
|
Doedens, J. R., and K. Kirkegaard.
1995.
Inhibition of cellular protein secretion by poliovirus proteins 2B and 3A.
EMBO J.
14:894-907[Medline].
|
| 4.
|
Doedens, J. R.,
T. H. Giddings, Jr., and K. Kirkegaard.
1997.
Inhibition of endoplasmic reticulum-to-Golgi traffic by poliovirus protein 3A: genetic and ultrastructural analysis.
J. Virol.
71:9054-9064[Abstract].
|
| 5.
|
Domingo, E.,
M. G. Mateu,
C. Escarmis,
E. Martinez-Salas,
D. Andreu,
E. Giralt,
N. Verdaguer, and I. Fita.
1996.
Molecular evolution of aphthoviruses.
Virus Genes
11:197-207.
|
| 6.
|
Dunn, C. S., and A. I. Donaldson.
1997.
Natural adaptation to pigs of a Taiwanese isolate of foot-and-mouth disease virus.
Vet. Rec.
141:174-175[Free Full Text].
|
| 7.
|
Escarmís, C.,
E. E. C. Carrillo,
M. Ferrer,
J. F. G. Arriaza,
N. Lopez,
C. Tami,
N. Verdaguer,
E. Domingo, and M. T. Franze-Fernandez.
1998.
Rapid selection in modified BHK-21 cells of a foot-and-mouth disease virus variant showing alterations in cell tropism.
J. Virol.
72:10171-10179[Abstract/Free Full Text].
|
| 8.
|
Forss, S.,
K. Strebel,
E. Beck, and H. Schaller.
1984.
Nucleotide sequence and genome organization of foot-and-mouth disease virus.
Nucleic Acids Res.
12:6587-6601[Abstract/Free Full Text].
|
| 9.
|
Giraudo, A. T.,
E. Beck,
K. Strebel,
P. Augé de Mello,
J. L. La Torre,
E. A. Scodeller, and I. E. Bergmann.
1990.
Identification of a nucleotide deletion in parts of polypeptide 3A in two independent attenuated aphthovirus strains.
Virology
177:780-783[CrossRef][Medline].
|
| 10.
|
Graff, J.,
A. Normann,
S. M. Feinstone, and B. Flehmig.
1994.
Nucleotide sequence of wild-type hepatitis A virus GBM in comparison with two cell culture-adapted variants.
J. Virol.
68:548-554[Abstract/Free Full Text].
|
| 11.
|
Graff, J.,
C. Kasang,
A. Normann,
M. Pfisterer-Hunt,
S. M. Feinstone, and B. Flehmig.
1994.
Mutational events in consecutive passages of hepatitis A virus strain GBM during cell culture adaptation.
Virology
204:60-68[CrossRef][Medline].
|
| 12.
|
Higuchi, R.,
B. Krummel, and R. K. Saiki.
1988.
A general method of in vitro preparation and specific mutation of DNA fragments: study of protein and DNA interactions.
Nucleic Acids Res.
16:7351-7367[Abstract/Free Full Text].
|
| 13.
|
Kitching, R. P.
1999.
Foot-and-mouth disease: current world situation.
Vaccine
17:1772-1774[CrossRef][Medline].
|
| 14.
|
Lama, J.,
M. A. Sanz, and L. Carrasco.
1998.
Genetic analysis of poliovirus protein 3A: characterization of a non-cytopathic mutant virus defective in killing Vero cells.
J. Gen. Virol.
79:1911-1921[Abstract].
|
| 15.
|
Lemon, S. M.,
P. C. Murphy,
P. A. Shields,
L. H. Ping,
S. M. Feinstone,
T. Cromeans, and R. W. Jansen.
1991.
Antigenic and genetic variation in hepatitis A virus variants arising during persistent infection: evidence for genetic recombination.
J. Virol.
65:2056-2065[Abstract/Free Full Text].
|
| 16.
|
Logan, D.,
R. Abu-Ghazaleh,
W. Blakemore,
S. Curry,
T. Jackson,
A. King,
S. Lea,
R. Lewis,
J. Newman,
N. Parry,
D. Rowlands,
D. Stuart, and E. Fry.
1993.
Structure of the major immunogenic site on foot-and-mouth disease virus.
Nature
362:566-568[CrossRef][Medline].
|
| 17.
|
Mason, P. W.,
E. Rieder, and B. Baxt.
1994.
RGD sequence of foot-and-mouth disease virus is essential for infecting cells via the natural receptor but can be bypassed by an antibody-dependent enhancement pathway.
Proc. Natl. Acad. Sci. USA
91:1932-1936[Abstract/Free Full Text].
|
| 18.
|
Mason, P. W.,
M. E. Piccone,
T. S. McKenna,
J. Chinsangaram, and M. J. Grubman.
1997.
Evaluation of a live-attenuated foot-and-mouth disease virus as a vaccine candidate.
Virology
227:96-102[CrossRef][Medline].
|
| 19.
|
Morace, G.,
G. Pisani,
F. Beneduce,
M. Divizia, and A. Panà.
1993.
Mutations in the 3A genomic region of two cytopathic strains of hepatitis A virus isolated in Italy.
Virus Res.
28:187-194[CrossRef][Medline].
|
| 20.
|
Neff, S.,
D. Sá- Carvalho,
E. Rieder,
P. W. Mason,
S. D. Blystone,
E. J. Brown, and B. Baxt.
1998.
Foot-and-mouth disease virus virulent for cattle utilizes the integrin alpha(v)beta3 as its receptor.
J. Virol.
72:3587-3594[Abstract/Free Full Text].
|
| 21.
|
Parisi, J. M.,
P. Costa Giomi,
P. Grigera,
P. Augé de Mello,
I. E. Bergmann,
J. L. La Torre, and E. A. Schodeller.
1985.
Biochemical characterization of an aphthovirus type O1 strain Campos attenuated for cattle by serial passages in chicken embryos.
Virology
147:61-71[CrossRef][Medline].
|
| 22.
|
Pereira, H. G.
1981.
Foot-and-mouth disease, p. 333-363.
In
E. P. J. Gibbs (ed.), Virus diseases of food animals. Academic Press, Inc., New York, N.Y.
|
| 23.
|
Rieder, E.,
T. Bunch,
F. Brown, and P. W. Mason.
1993.
Genetically engineered foot-and-mouth disease viruses with poly(C) tracts of two nucleotides are virulent in mice.
J. Virol.
67:5139-5145[Abstract/Free Full Text].
|
| 24.
|
Robertson, B. H.,
M. J. Grubman,
G. N. Weddell,
D. M. Moore,
J. D. Welsh,
T. Fischer,
D. J. Dowbenko,
D. G. Yansura,
B. Small, and D. G. Kleid.
1985.
Nucleotide and amino acid sequence coding for polypeptides of foot-and-mouth disease virus type A12.
J. Virol.
54:651-660[Abstract/Free Full Text].
|
| 25.
|
Sá-Carvalho, D.,
E. Rieder,
B. Baxt,
R. Rodarte,
A. Tanuri, and P. W. Mason.
1997.
Tissue culture adaptation of foot-and-mouth disease virus selects viruses that bind to heparin and are attenuated in cattle.
J. Virol.
71:5115-5123[Abstract].
|
| 26.
|
Sagedahl, A.,
A. T. Giraudo,
P. Augé de Mello,
I. E. Bergmann,
J. L. La Torre, and E. A. Schodeller.
1987.
Biochemical characterization of an aphthovirus type C3 strain Resende attenuated for cattle by serial passages in chicken embryos.
Virology
157:366-374[CrossRef][Medline].
|
| 27.
|
Tellier, R.,
J. Bukh,
S. U. Emerson, and R. H. Purcell.
1996.
Amplification of full-length hepatitis A virus genome by long reverse transcription-PCR and transcription of infectious RNA directly from the amplicon.
Proc. Natl. Acad. Sci. USA
93:4370-4371[Abstract/Free Full Text].
|
| 28.
|
Wimmer, E.,
C. U. T. Hellen, and X. M. Cao.
1993.
Genetics of poliovirus.
Annu. Rev. Genet.
27:353-436[CrossRef][Medline].
|
| 29.
|
Xiang, W.,
A. Cuconati,
D. Hope,
K. Kirkegaard, and E. Wimmer.
1998.
Complete protein linkage map of poliovirus P3 proteins: interaction of polymerase 3Dpol with VPg and with genetic variants of 3AB.
J. Virol.
72:6732-6741[Abstract/Free Full Text].
|
Journal of Virology, January 2000, p. 987-991, Vol. 74, No. 2
0022-538X/00/$04.00+0
This article has been cited by other articles:
-
De Palma, A. M., Thibaut, H. J., van der Linden, L., Lanke, K., Heggermont, W., Ireland, S., Andrews, R., Arimilli, M., Al-Tel, T. H., De Clercq, E., van Kuppeveld, F., Neyts, J.
(2009). Mutations in the Nonstructural Protein 3A Confer Resistance to the Novel Enterovirus Replication Inhibitor TTP-8307. Antimicrob. Agents Chemother.
53: 1850-1857
[Abstract]
[Full Text]
-
Hales, L. M., Knowles, N. J., Reddy, P. S., Xu, L., Hay, C., Hallenbeck, P. L.
(2008). Complete genome sequence analysis of Seneca Valley virus-001, a novel oncolytic picornavirus. J. Gen. Virol.
89: 1265-1275
[Abstract]
[Full Text]
-
Nunez, J. I., Molina, N., Baranowski, E., Domingo, E., Clark, S., Burman, A., Berryman, S., Jackson, T., Sobrino, F.
(2007). Guinea Pig-Adapted Foot-and-Mouth Disease Virus with Altered Receptor Recognition Can Productively Infect a Natural Host. J. Virol.
81: 8497-8506
[Abstract]
[Full Text]
-
Wessels, E., Duijsings, D., Lanke, K. H. W., van Dooren, S. H. J., Jackson, C. L., Melchers, W. J. G., van Kuppeveld, F. J. M.
(2006). Effects of Picornavirus 3A Proteins on Protein Transport and GBF1-Dependent COP-I Recruitment. J. Virol.
80: 11852-11860
[Abstract]
[Full Text]
-
Kim, M.-C., Kwon, Y.-K., Joh, S.-J., Lindberg, A. M., Kwon, J.-H., Kim, J.-H., Kim, S.-J.
(2006). Molecular analysis of duck hepatitis virus type 1 reveals a novel lineage close to the genus Parechovirus in the family Picornaviridae.. J. Gen. Virol.
87: 3307-3316
[Abstract]
[Full Text]
-
Harris, J. R., Racaniello, V. R.
(2005). Amino Acid Changes in Proteins 2B and 3A Mediate Rhinovirus Type 39 Growth in Mouse Cells. J. Virol.
79: 5363-5373
[Abstract]
[Full Text]
-
Grubman, M. J., Baxt, B.
(2004). Foot-and-Mouth Disease. Clin. Microbiol. Rev.
17: 465-493
[Abstract]
[Full Text]
-
van Rensburg, H. G., Henry, T. M., Mason, P. W.
(2004). Studies of genetically defined chimeras of a European type A virus and a South African Territories type 2 virus reveal growth determinants for foot-and-mouth disease virus. J. Gen. Virol.
85: 61-68
[Abstract]
[Full Text]
-
Pacheco, J. M., Henry, T. M., O'Donnell, V. K., Gregory, J. B., Mason, P. W.
(2003). Role of Nonstructural Proteins 3A and 3B in Host Range and Pathogenicity of Foot-and-Mouth Disease Virus. J. Virol.
77: 13017-13027
[Abstract]
[Full Text]
-
Mason, P. W., Pacheco, J. M., Zhao, Q.-Z., Knowles, N. J.
(2003). Comparisons of the complete genomes of Asian, African and European isolates of a recent foot-and-mouth disease virus type O pandemic strain (PanAsia). J. Gen. Virol.
84: 1583-1593
[Abstract]
[Full Text]
-
Johansson, E. S., Niklasson, B., Tesh, R. B., Shafren, D. R., Travassos da Rosa, A. P. A., Lindberg, A. M.
(2003). Molecular characterization of M1146, an American isolate of Ljungan virus (LV) reveals the presence of a new LV genotype. J. Gen. Virol.
84: 837-844
[Abstract]
[Full Text]
-
Zhao, Q., Pacheco, J. M., Mason, P. W.
(2003). Evaluation of Genetically Engineered Derivatives of a Chinese Strain of Foot-and-Mouth Disease Virus Reveals a Novel Cell-Binding Site Which Functions in Cell Culture and in Animals. J. Virol.
77: 3269-3280
[Abstract]
[Full Text]
-
Duque, H., Baxt, B.
(2003). Foot-and-Mouth Disease Virus Receptors: Comparison of Bovine {alpha}V Integrin Utilization by Type A and O Viruses. J. Virol.
77: 2500-2511
[Abstract]
[Full Text]
-
Chung, W.-B., Sorensen, K. J., Liao, P.-C., Yang, P.-C., Jong, M.-H.
(2002). Differentiation of Foot-and-Mouth Disease Virus-Infected from Vaccinated Pigs by Enzyme-Linked Immunosorbent Assay Using Nonstructural Protein 3AB as the Antigen and Application to an Eradication Program. J. Clin. Microbiol.
40: 2843-2848
[Abstract]
[Full Text]
-
Hughes, G. J., Mioulet, V., Haydon, D. T., Kitching, R. P., Donaldson, A. I., Woolhouse, M. E. J.
(2002). Serial passage of foot-and-mouth disease virus in sheep reveals declining levels of viraemia over time. J. Gen. Virol.
83: 1907-1914
[Abstract]
[Full Text]
-
Johansson, S., Niklasson, B., Maizel, J., Gorbalenya, A. E., Lindberg, A. M.
(2002). Molecular Analysis of Three Ljungan Virus Isolates Reveals a New, Close-to-Root Lineage of the Picornaviridae with a Cluster of Two Unrelated 2A Proteins. J. Virol.
76: 8920-8930
[Abstract]
[Full Text]
-
Núñez, J. I., Baranowski, E., Molina, N., Ruiz-Jarabo, C. M., Sánchez, C., Domingo, E., Sobrino, F.
(2001). A Single Amino Acid Substitution in Nonstructural Protein 3A Can Mediate Adaptation of Foot-and-Mouth Disease Virus to the Guinea Pig. J. Virol.
75: 3977-3983
[Abstract]
[Full Text]
-
Knowles, N. J., Davies, P. R., Henry, T., O'Donnell, V., Pacheco, J. M., Mason, P. W.
(2001). Emergence in Asia of Foot-and-Mouth Disease Viruses with Altered Host Range: Characterization of Alterations in the 3A Protein. J. Virol.
75: 1551-1556
[Abstract]
[Full Text]
-
Alexandersen, S., Forsyth, M. A., Reid, S. M., Belsham, G. J.
(2000). Development of Reverse Transcription-PCR (Oligonucleotide Probing) Enzyme-Linked Immunosorbent Assays for Diagnosis and Preliminary Typing of Foot-and-Mouth Disease: a New System Using Simple and Aqueous-Phase Hybridization. J. Clin. Microbiol.
38: 4604-4613
[Abstract]
[Full Text]
-
Neff, S., Mason, P. W., Baxt, B.
(2000). High-Efficiency Utilization of the Bovine Integrin alpha vbeta 3 as a Receptor for Foot-and-Mouth Disease Virus Is Dependent on the Bovine beta 3 Subunit. J. Virol.
74: 7298-7306
[Abstract]
[Full Text]
-
Heise, M. T., Simpson, D. A., Johnston, R. E.
(2000). A Single Amino Acid Change in nsP1 Attenuates Neurovirulence of the Sindbis-Group Alphavirus S.A.AR86. J. Virol.
74: 4207-4213
[Abstract]
[Full Text]
Top
Abstract
Text
