Binding site on the transferrin receptor for the parvovirus capsid and effects of altered affinity on cell uptake and infection

Laura B. Goodman, Sangbom M. Lyi, Natalie C. Johnson, Javier O. Cifuente, Susan L. Hafenstein, Colin R. Parrish

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Canine parvovirus (CPV) and its relative feline panleukopenia virus (FPV) bind the transferrin receptor type 1 (TfR) to infect their host cells but show differences in the interactions with the feline and canine TfRs that determine viral host range and tissue tropism. We changed apical and protease-like domain residues by introducing point mutations and adding or removing glycosylation signals, and we then examined the interactions of those mutant TfRs with the capsids. Most substitutions had little effect on virus binding and uptake. However, mutations of several sites in the apical domain of the receptor either prevented binding to the capsids or reduced the affinity of receptor binding to various degrees. Glycans within the virus binding face of the apical domain also controlled capsid binding. CPV, but not the related feline parvovirus, could use receptors containing a canine TfR-specific glycosylation to mediate efficient infection, while addition of other N-linked glycosylation sites into the virus binding face of the feline apical domain reduced or eliminated both binding and infection. Replacement of critical feline TfR residue 221 with every amino acid had effects on binding and infection which were significantly associated with the biochemical properties of the residue replaced. Receptors with reduced affinities mostly showed proportional changes in their ability to mediate infection. Testing feline TfR variants for their binding and uptake patterns in cells showed that low-affinity versions bound fewer capsids and also differed in attachment to the cell surface and filopodia, but transport to the perinuclear endosome was similar.

Original languageEnglish (US)
Pages (from-to)4969-4978
Number of pages10
JournalJournal of virology
Volume84
Issue number10
DOIs
StatePublished - May 1 2010

Fingerprint

Parvovirus
Protoparvovirus
Transferrin Receptors
capsid
Capsid
Felidae
transferrin
Virus Attachment
binding sites
Feline Panleukopenia Virus
Binding Sites
Canine Parvovirus
Glycosylation
uptake mechanisms
receptors
Infection
infection
Carnivore protoparvovirus 1
Canidae
glycosylation

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Goodman, Laura B. ; Lyi, Sangbom M. ; Johnson, Natalie C. ; Cifuente, Javier O. ; Hafenstein, Susan L. ; Parrish, Colin R. / Binding site on the transferrin receptor for the parvovirus capsid and effects of altered affinity on cell uptake and infection. In: Journal of virology. 2010 ; Vol. 84, No. 10. pp. 4969-4978.
@article{cc8f86590a3e4a24883ea3f217bb64e2,
title = "Binding site on the transferrin receptor for the parvovirus capsid and effects of altered affinity on cell uptake and infection",
abstract = "Canine parvovirus (CPV) and its relative feline panleukopenia virus (FPV) bind the transferrin receptor type 1 (TfR) to infect their host cells but show differences in the interactions with the feline and canine TfRs that determine viral host range and tissue tropism. We changed apical and protease-like domain residues by introducing point mutations and adding or removing glycosylation signals, and we then examined the interactions of those mutant TfRs with the capsids. Most substitutions had little effect on virus binding and uptake. However, mutations of several sites in the apical domain of the receptor either prevented binding to the capsids or reduced the affinity of receptor binding to various degrees. Glycans within the virus binding face of the apical domain also controlled capsid binding. CPV, but not the related feline parvovirus, could use receptors containing a canine TfR-specific glycosylation to mediate efficient infection, while addition of other N-linked glycosylation sites into the virus binding face of the feline apical domain reduced or eliminated both binding and infection. Replacement of critical feline TfR residue 221 with every amino acid had effects on binding and infection which were significantly associated with the biochemical properties of the residue replaced. Receptors with reduced affinities mostly showed proportional changes in their ability to mediate infection. Testing feline TfR variants for their binding and uptake patterns in cells showed that low-affinity versions bound fewer capsids and also differed in attachment to the cell surface and filopodia, but transport to the perinuclear endosome was similar.",
author = "Goodman, {Laura B.} and Lyi, {Sangbom M.} and Johnson, {Natalie C.} and Cifuente, {Javier O.} and Hafenstein, {Susan L.} and Parrish, {Colin R.}",
year = "2010",
month = "5",
day = "1",
doi = "10.1128/JVI.02623-09",
language = "English (US)",
volume = "84",
pages = "4969--4978",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "10",

}

Binding site on the transferrin receptor for the parvovirus capsid and effects of altered affinity on cell uptake and infection. / Goodman, Laura B.; Lyi, Sangbom M.; Johnson, Natalie C.; Cifuente, Javier O.; Hafenstein, Susan L.; Parrish, Colin R.

In: Journal of virology, Vol. 84, No. 10, 01.05.2010, p. 4969-4978.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Binding site on the transferrin receptor for the parvovirus capsid and effects of altered affinity on cell uptake and infection

AU - Goodman, Laura B.

AU - Lyi, Sangbom M.

AU - Johnson, Natalie C.

AU - Cifuente, Javier O.

AU - Hafenstein, Susan L.

AU - Parrish, Colin R.

PY - 2010/5/1

Y1 - 2010/5/1

N2 - Canine parvovirus (CPV) and its relative feline panleukopenia virus (FPV) bind the transferrin receptor type 1 (TfR) to infect their host cells but show differences in the interactions with the feline and canine TfRs that determine viral host range and tissue tropism. We changed apical and protease-like domain residues by introducing point mutations and adding or removing glycosylation signals, and we then examined the interactions of those mutant TfRs with the capsids. Most substitutions had little effect on virus binding and uptake. However, mutations of several sites in the apical domain of the receptor either prevented binding to the capsids or reduced the affinity of receptor binding to various degrees. Glycans within the virus binding face of the apical domain also controlled capsid binding. CPV, but not the related feline parvovirus, could use receptors containing a canine TfR-specific glycosylation to mediate efficient infection, while addition of other N-linked glycosylation sites into the virus binding face of the feline apical domain reduced or eliminated both binding and infection. Replacement of critical feline TfR residue 221 with every amino acid had effects on binding and infection which were significantly associated with the biochemical properties of the residue replaced. Receptors with reduced affinities mostly showed proportional changes in their ability to mediate infection. Testing feline TfR variants for their binding and uptake patterns in cells showed that low-affinity versions bound fewer capsids and also differed in attachment to the cell surface and filopodia, but transport to the perinuclear endosome was similar.

AB - Canine parvovirus (CPV) and its relative feline panleukopenia virus (FPV) bind the transferrin receptor type 1 (TfR) to infect their host cells but show differences in the interactions with the feline and canine TfRs that determine viral host range and tissue tropism. We changed apical and protease-like domain residues by introducing point mutations and adding or removing glycosylation signals, and we then examined the interactions of those mutant TfRs with the capsids. Most substitutions had little effect on virus binding and uptake. However, mutations of several sites in the apical domain of the receptor either prevented binding to the capsids or reduced the affinity of receptor binding to various degrees. Glycans within the virus binding face of the apical domain also controlled capsid binding. CPV, but not the related feline parvovirus, could use receptors containing a canine TfR-specific glycosylation to mediate efficient infection, while addition of other N-linked glycosylation sites into the virus binding face of the feline apical domain reduced or eliminated both binding and infection. Replacement of critical feline TfR residue 221 with every amino acid had effects on binding and infection which were significantly associated with the biochemical properties of the residue replaced. Receptors with reduced affinities mostly showed proportional changes in their ability to mediate infection. Testing feline TfR variants for their binding and uptake patterns in cells showed that low-affinity versions bound fewer capsids and also differed in attachment to the cell surface and filopodia, but transport to the perinuclear endosome was similar.

UR - http://www.scopus.com/inward/record.url?scp=77951467569&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77951467569&partnerID=8YFLogxK

U2 - 10.1128/JVI.02623-09

DO - 10.1128/JVI.02623-09

M3 - Article

C2 - 20200243

AN - SCOPUS:77951467569

VL - 84

SP - 4969

EP - 4978

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 10

ER -