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Journal of Virology, December 1999, p. 10051-10060, Vol. 73, No. 12
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Soluble Forms of the Subgroup A Avian Leukosis
Virus [ALV(A)] Receptor Tva Significantly Inhibit ALV(A)
Infection In Vitro and In Vivo
Sheri L.
Holmen,1
Donald W.
Salter,2
William S.
Payne,3
Jerry B.
Dodgson,3
Stephen H.
Hughes,4 and
Mark J.
Federspiel1,*
Molecular Medicine Program, Mayo Clinic and
Mayo Foundation, Rochester, Minnesota 559051;
Department of Biological Sciences, University of West Alabama,
Livingston, Alabama 354702; Department
of Microbiology, Michigan State University, East Lansing, Michigan
488243; and ABL-Basic Research
Program, NCI-Frederick Cancer Research and Development Center,
Frederick, Maryland 217024
Received 15 April 1999/Accepted 8 September 1999
The interactions between the subgroup A avian leukosis virus
[ALV(A)] envelope glycoproteins and soluble forms of the ALV(A) receptor Tva were analyzed both in vitro and in vivo by quantitating the ability of the soluble Tva proteins to inhibit ALV(A) entry into
susceptible cells. Two soluble Tva proteins were tested: the
83-amino-acid Tva extracellular region fused to two epitope tags (sTva)
or fused to the constant region of the mouse immunoglobulin G heavy
chain (sTva-mIgG). Replication-competent ALV-based retroviral vectors
with subgroup B or C env were used to deliver and express the two soluble tv-a (stva) genes in avian
cells. In vitro, chicken embryo fibroblasts or DF-1 cells expressing
sTva or sTva-mIgG proteins were much more resistant to infection by
ALV(A) (~200-fold) than were control cells infected by only the
vector. The antiviral effect was specific for ALV(A), which is
consistent with a receptor interference mechanism. The antiviral effect
of sTva-mIgG was positively correlated with the amount of sTva-mIgG
protein. In vivo, the stva genes were delivered and
expressed in line 0 chicken embryos by the ALV(B)-based vector
RCASBP(B). Viremic chickens expressed relatively high levels of
stva and stva-mIgG RNA in a broad range of
tissues. High levels of sTva-mIgG protein were detected in the sera of
chickens infected with RCASBP(B)stva-mIgG. Viremic chickens infected
with RCASBP(B) alone, RCASBP(B)stva, or RCASBP(B)stva-mIgG were
challenged separately with ALV(A) and ALV(C). Both sTva and sTva-mIgG
significantly inhibited infection by ALV(A) (95 and 100% respectively)
but had no measurable effect on ALV(C) infection. The results of this
study indicate that a soluble receptor can effectively block infection
of at least some retroviruses and demonstrates the utility of the ALV
experimental system in characterizing the mechanism(s) of viral entry.
*
Corresponding author. Mailing address: Molecular
Medicine Program, Mayo Clinic and Mayo Foundation, Guggenheim 1842, 200 First St., SW, Rochester, MN 55905. Phone: (507) 284-8895. Fax: (507) 266-2122. E-mail: federspiel.mark{at}mayo.edu.
Journal of Virology, December 1999, p. 10051-10060, Vol. 73, No. 12
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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