Mechanisms of avian retroviral host range extension

G. Jonah A Rainey, Andrew Natonson, Lori F. Maxfield, John M. Coffin

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Alpharetroviruses provide a useful system for the study of the molecular mechanisms of host range and receptor interaction. These viruses can be divided into subgroups based on diverse receptor usage due to variability within the two host range determining regions, hr1 and hr2, in their envelope glycoprotein SU (gp85). In previous work, our laboratory described selection from a subgroup B avian sarcoma-leukosis virus of an extended-host-range variant (LT/SI) with two adjacent amino acid substitutions in hr1. This virus retains its ability to use the subgroup BD receptor but can also infect QT6/BD cells, which bear a related subgroup E receptor (R. A. Taplitz and J. M. Coffin, J. Virol 71:7814-7819, 1997). Here, we report further analysis of this unusual variant. First, one (L154S) of the two substitutions is sufficient for host range extension, while the other (T155I) does not alter host range. Second, these mutations extend host range to non-avian cell types, including human, dog, cat, mouse, rat, and hamster. Third, interference experiments imply that the mutants interact efficiently with the subgroup BD receptor and possibly the related subgroup E receptor, but they have another means of entry that is not dependent on these interactions. Fourth, binding studies indicate that the mutant SU proteins retain the ability to interact as monomers with subgroup BD and BDE receptors but only bind the subgroup E receptor in the context of an Env trimer. Further, the mutant SU proteins bind well to chicken cells but do not bind any better than wild-type subgroup B to QT6 or human cells, even though the corresponding viruses are capable of infecting these cells.

Original languageEnglish (US)
Pages (from-to)6709-6719
Number of pages11
JournalJournal of virology
Volume77
Issue number12
DOIs
StatePublished - Jun 1 2003
Externally publishedYes

Fingerprint

Host Specificity
host range
receptors
Mutant Proteins
Viruses
viruses
Avian Leukosis
Alpharetrovirus
Avian Sarcoma Viruses
mutants
avian sarcoma
cells
Cercopithecine Herpesvirus 1
Amino Acid Substitution
Cricetinae
Chickens
Glycoproteins
amino acid substitution
Cats
crossover interference

ASJC Scopus subject areas

  • Immunology

Cite this

Mechanisms of avian retroviral host range extension. / Rainey, G. Jonah A; Natonson, Andrew; Maxfield, Lori F.; Coffin, John M.

In: Journal of virology, Vol. 77, No. 12, 01.06.2003, p. 6709-6719.

Research output: Contribution to journalArticle

Rainey, G. Jonah A ; Natonson, Andrew ; Maxfield, Lori F. ; Coffin, John M. / Mechanisms of avian retroviral host range extension. In: Journal of virology. 2003 ; Vol. 77, No. 12. pp. 6709-6719.
@article{21b7410893954be69c4c1b3e96e416c9,
title = "Mechanisms of avian retroviral host range extension",
abstract = "Alpharetroviruses provide a useful system for the study of the molecular mechanisms of host range and receptor interaction. These viruses can be divided into subgroups based on diverse receptor usage due to variability within the two host range determining regions, hr1 and hr2, in their envelope glycoprotein SU (gp85). In previous work, our laboratory described selection from a subgroup B avian sarcoma-leukosis virus of an extended-host-range variant (LT/SI) with two adjacent amino acid substitutions in hr1. This virus retains its ability to use the subgroup BD receptor but can also infect QT6/BD cells, which bear a related subgroup E receptor (R. A. Taplitz and J. M. Coffin, J. Virol 71:7814-7819, 1997). Here, we report further analysis of this unusual variant. First, one (L154S) of the two substitutions is sufficient for host range extension, while the other (T155I) does not alter host range. Second, these mutations extend host range to non-avian cell types, including human, dog, cat, mouse, rat, and hamster. Third, interference experiments imply that the mutants interact efficiently with the subgroup BD receptor and possibly the related subgroup E receptor, but they have another means of entry that is not dependent on these interactions. Fourth, binding studies indicate that the mutant SU proteins retain the ability to interact as monomers with subgroup BD and BDE receptors but only bind the subgroup E receptor in the context of an Env trimer. Further, the mutant SU proteins bind well to chicken cells but do not bind any better than wild-type subgroup B to QT6 or human cells, even though the corresponding viruses are capable of infecting these cells.",
author = "Rainey, {G. Jonah A} and Andrew Natonson and Maxfield, {Lori F.} and Coffin, {John M.}",
year = "2003",
month = "6",
day = "1",
doi = "10.1128/JVI.77.12.6709-6719.2003",
language = "English (US)",
volume = "77",
pages = "6709--6719",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "12",

}

TY - JOUR

T1 - Mechanisms of avian retroviral host range extension

AU - Rainey, G. Jonah A

AU - Natonson, Andrew

AU - Maxfield, Lori F.

AU - Coffin, John M.

PY - 2003/6/1

Y1 - 2003/6/1

N2 - Alpharetroviruses provide a useful system for the study of the molecular mechanisms of host range and receptor interaction. These viruses can be divided into subgroups based on diverse receptor usage due to variability within the two host range determining regions, hr1 and hr2, in their envelope glycoprotein SU (gp85). In previous work, our laboratory described selection from a subgroup B avian sarcoma-leukosis virus of an extended-host-range variant (LT/SI) with two adjacent amino acid substitutions in hr1. This virus retains its ability to use the subgroup BD receptor but can also infect QT6/BD cells, which bear a related subgroup E receptor (R. A. Taplitz and J. M. Coffin, J. Virol 71:7814-7819, 1997). Here, we report further analysis of this unusual variant. First, one (L154S) of the two substitutions is sufficient for host range extension, while the other (T155I) does not alter host range. Second, these mutations extend host range to non-avian cell types, including human, dog, cat, mouse, rat, and hamster. Third, interference experiments imply that the mutants interact efficiently with the subgroup BD receptor and possibly the related subgroup E receptor, but they have another means of entry that is not dependent on these interactions. Fourth, binding studies indicate that the mutant SU proteins retain the ability to interact as monomers with subgroup BD and BDE receptors but only bind the subgroup E receptor in the context of an Env trimer. Further, the mutant SU proteins bind well to chicken cells but do not bind any better than wild-type subgroup B to QT6 or human cells, even though the corresponding viruses are capable of infecting these cells.

AB - Alpharetroviruses provide a useful system for the study of the molecular mechanisms of host range and receptor interaction. These viruses can be divided into subgroups based on diverse receptor usage due to variability within the two host range determining regions, hr1 and hr2, in their envelope glycoprotein SU (gp85). In previous work, our laboratory described selection from a subgroup B avian sarcoma-leukosis virus of an extended-host-range variant (LT/SI) with two adjacent amino acid substitutions in hr1. This virus retains its ability to use the subgroup BD receptor but can also infect QT6/BD cells, which bear a related subgroup E receptor (R. A. Taplitz and J. M. Coffin, J. Virol 71:7814-7819, 1997). Here, we report further analysis of this unusual variant. First, one (L154S) of the two substitutions is sufficient for host range extension, while the other (T155I) does not alter host range. Second, these mutations extend host range to non-avian cell types, including human, dog, cat, mouse, rat, and hamster. Third, interference experiments imply that the mutants interact efficiently with the subgroup BD receptor and possibly the related subgroup E receptor, but they have another means of entry that is not dependent on these interactions. Fourth, binding studies indicate that the mutant SU proteins retain the ability to interact as monomers with subgroup BD and BDE receptors but only bind the subgroup E receptor in the context of an Env trimer. Further, the mutant SU proteins bind well to chicken cells but do not bind any better than wild-type subgroup B to QT6 or human cells, even though the corresponding viruses are capable of infecting these cells.

UR - http://www.scopus.com/inward/record.url?scp=0037604693&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037604693&partnerID=8YFLogxK

U2 - 10.1128/JVI.77.12.6709-6719.2003

DO - 10.1128/JVI.77.12.6709-6719.2003

M3 - Article

VL - 77

SP - 6709

EP - 6719

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 12

ER -