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Journal of Virology, July 2000, p. 5754-5761, Vol. 74, No. 13
Program in Molecular and Cellular
Biology1 and Departments of Comparative
Medicine2 and
Microbiology,3 University of Washington,
and Division of Human Biology, Fred Hutchinson Cancer Research
Center,4 Seattle, Washington
Received 19 January 2000/Accepted 31 March 2000
The envelope protein is a primary pathogenic determinant for
T-cell-tropic feline leukemia virus (FeLV) variants, the best studied
of which is the immunodeficiency-inducing virus, 61C. We have
previously demonstrated that T-cell-tropic, cytopathic, and
syncytium-inducing viruses evolve in cats infected with a relatively
avirulent, transmissible form of FeLV, 61E. The envelope gene of an 81T
variant, which encoded scattered single-amino-acid changes throughout
the envelope as well as a 4-amino-acid insertion in the C-terminal half
of the surface unit (SU) of envelope, was sufficient to confer the
T-cell-tropic, cytopathic phenotype (J. L. Rohn, M. S. Moser,
S. R. Gwynn, D. N. Baldwin, and J. Overbaugh, J. Virol.
72:2686-2696, 1998). In the present study, we examined the role of the
4-amino-acid insertion in determining viral replication and tropism of
FeLV-81T. The 4-amino-acid insertion was found to be functionally
equivalent to a 6-amino-acid insertion at an identical location in the
61C variant. However, viruses expressing a chimeric 61E/81T SU,
containing the insertion together with the N terminus of 61E SU, were
found to be replication defective and were impaired in the processing
of the envelope precursor into the functional SU and transmembrane (TM)
proteins. In approximately 10% of cultured feline T cells (3201)
transfected with the 61E/81T envelope chimeras and maintained over
time, replication-competent tissue culture-adapted variants were
isolated. Compensatory mutations in the SU of the tissue
culture-adapted viruses were identified at positions 7 and 375, and
each was shown to restore envelope protein processing when combined
with the C-terminal 81T insertion. Unexpectedly, these viruses
displayed different phenotypes in feline T cells: the virus with a
change from glutamine to proline at position 7 acquired a
T-cell-tropic, cytopathic phenotype, whereas the virus with a change
from valine to leucine at position 375 had slower replication kinetics
and caused no cytopathic effects. Given the differences in the
replication properties of these viruses, it is noteworthy that the
insertion as well as the two single-amino-acid changes all occur
outside of predicted FeLV receptor-binding domains.
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Feline Leukemia Virus Envelope Sequences That
Affect T-Cell Tropism and Syncytium Formation Are Not Part of Known
Receptor-Binding Domains
*
Corresponding author. Mailing address: Division of
Human Biology, Fred Hutchinson Cancer Center, 1100 Fairview Ave. N.,
C3-168, Seattle, WA 98109-1024. Phone: (206) 667-3524. Fax: (206)
667-1535. E-mail: joverbau{at}fhcrc.org.
This paper is dedicated to the memory of our friend and colleague,
Samuel Rudolph Gwynn.
Deceased.
§
Present address: Leadd BV, 2300 AA Leiden, The Netherlands.
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