In vivo characterization of the integrin β3 as a receptor for Hantaan virus cellular entry

Jin Won Song, Ki-Joon Song, Luck Ju Baek, Blasie Frost, Mortimer Poncz, KwangSook Park

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Binding of viruses to cell surface molecules is an essential step in viral infection. In vitro studies suggested that the αvβ 3 integrin receptor is the epithelial cell receptor for Hantaan virus (HTNV). Whether β3 is in vivo the only or central cellular receptor for HTNV infection is not known. To investigate the role of β3 integrin for cellular entry of HTNV, we established an HTNV infection model in newborn murine pups. Infected pups died at an average age of 14.2 ± 1.1 days with high levels of viral antigen detected in their brain, lung, and kidney. Pre-injection of blocking monoclonal antibodies (mAb) specific for either β3 or αV prolonged survival significantly to a maximal average survival of 19.7 ± 1.5 days (P < 0.01) and 18.4 ± 0.9 days (P < 0.01), respectively. XT-199, a chemical blocker of the αVβ3 receptor also prolonged survival to 19.5 ± 1.3 days (P < 0.01). In contrast to these receptor blockades, anti-HTNV antibody was not only able to prolong survival, but 20% of infected pups achieved long-term survival. An anti-murine β1 antibody comparatively prolonged survival (19.0 ± 1.2 days), suggesting that HTNV infection is partly mediated through integrin β1 receptors as well as through β3 receptors in vivo. Our data demonstrate that the β3 receptor is important for HTNV infection in vivo, but also suggest that HTNV may utilize additional receptors beyond β3 for cellular entry within an organism.

Original languageEnglish
Pages (from-to)121-127
Number of pages7
JournalExperimental and Molecular Medicine
Volume37
Issue number2
Publication statusPublished - 2005 Apr 30

Fingerprint

Hantaan virus
Virus Internalization
Viruses
Integrins
Virus Diseases
Virus Attachment
Blocking Antibodies
Viral Antigens
Antibodies
Epithelial Cells
Brain
Monoclonal Antibodies
Kidney
Lung
Injections

Keywords

  • Hantaan virus
  • Integrin β
  • Integrin β
  • Receptor
  • Viral entry

ASJC Scopus subject areas

  • Biochemistry
  • Genetics

Cite this

In vivo characterization of the integrin β3 as a receptor for Hantaan virus cellular entry. / Song, Jin Won; Song, Ki-Joon; Baek, Luck Ju; Frost, Blasie; Poncz, Mortimer; Park, KwangSook.

In: Experimental and Molecular Medicine, Vol. 37, No. 2, 30.04.2005, p. 121-127.

Research output: Contribution to journalArticle

Song, Jin Won ; Song, Ki-Joon ; Baek, Luck Ju ; Frost, Blasie ; Poncz, Mortimer ; Park, KwangSook. / In vivo characterization of the integrin β3 as a receptor for Hantaan virus cellular entry. In: Experimental and Molecular Medicine. 2005 ; Vol. 37, No. 2. pp. 121-127.
@article{889431c2d3dc4b2f82a8e41076e9de05,
title = "In vivo characterization of the integrin β3 as a receptor for Hantaan virus cellular entry",
abstract = "Binding of viruses to cell surface molecules is an essential step in viral infection. In vitro studies suggested that the αvβ 3 integrin receptor is the epithelial cell receptor for Hantaan virus (HTNV). Whether β3 is in vivo the only or central cellular receptor for HTNV infection is not known. To investigate the role of β3 integrin for cellular entry of HTNV, we established an HTNV infection model in newborn murine pups. Infected pups died at an average age of 14.2 ± 1.1 days with high levels of viral antigen detected in their brain, lung, and kidney. Pre-injection of blocking monoclonal antibodies (mAb) specific for either β3 or αV prolonged survival significantly to a maximal average survival of 19.7 ± 1.5 days (P < 0.01) and 18.4 ± 0.9 days (P < 0.01), respectively. XT-199, a chemical blocker of the αVβ3 receptor also prolonged survival to 19.5 ± 1.3 days (P < 0.01). In contrast to these receptor blockades, anti-HTNV antibody was not only able to prolong survival, but 20{\%} of infected pups achieved long-term survival. An anti-murine β1 antibody comparatively prolonged survival (19.0 ± 1.2 days), suggesting that HTNV infection is partly mediated through integrin β1 receptors as well as through β3 receptors in vivo. Our data demonstrate that the β3 receptor is important for HTNV infection in vivo, but also suggest that HTNV may utilize additional receptors beyond β3 for cellular entry within an organism.",
keywords = "Hantaan virus, Integrin β, Integrin β, Receptor, Viral entry",
author = "Song, {Jin Won} and Ki-Joon Song and Baek, {Luck Ju} and Blasie Frost and Mortimer Poncz and KwangSook Park",
year = "2005",
month = "4",
day = "30",
language = "English",
volume = "37",
pages = "121--127",
journal = "Experimental and Molecular Medicine",
issn = "1226-3613",
publisher = "Korean Society of Med. Biochemistry and Mol. Biology",
number = "2",

}

TY - JOUR

T1 - In vivo characterization of the integrin β3 as a receptor for Hantaan virus cellular entry

AU - Song, Jin Won

AU - Song, Ki-Joon

AU - Baek, Luck Ju

AU - Frost, Blasie

AU - Poncz, Mortimer

AU - Park, KwangSook

PY - 2005/4/30

Y1 - 2005/4/30

N2 - Binding of viruses to cell surface molecules is an essential step in viral infection. In vitro studies suggested that the αvβ 3 integrin receptor is the epithelial cell receptor for Hantaan virus (HTNV). Whether β3 is in vivo the only or central cellular receptor for HTNV infection is not known. To investigate the role of β3 integrin for cellular entry of HTNV, we established an HTNV infection model in newborn murine pups. Infected pups died at an average age of 14.2 ± 1.1 days with high levels of viral antigen detected in their brain, lung, and kidney. Pre-injection of blocking monoclonal antibodies (mAb) specific for either β3 or αV prolonged survival significantly to a maximal average survival of 19.7 ± 1.5 days (P < 0.01) and 18.4 ± 0.9 days (P < 0.01), respectively. XT-199, a chemical blocker of the αVβ3 receptor also prolonged survival to 19.5 ± 1.3 days (P < 0.01). In contrast to these receptor blockades, anti-HTNV antibody was not only able to prolong survival, but 20% of infected pups achieved long-term survival. An anti-murine β1 antibody comparatively prolonged survival (19.0 ± 1.2 days), suggesting that HTNV infection is partly mediated through integrin β1 receptors as well as through β3 receptors in vivo. Our data demonstrate that the β3 receptor is important for HTNV infection in vivo, but also suggest that HTNV may utilize additional receptors beyond β3 for cellular entry within an organism.

AB - Binding of viruses to cell surface molecules is an essential step in viral infection. In vitro studies suggested that the αvβ 3 integrin receptor is the epithelial cell receptor for Hantaan virus (HTNV). Whether β3 is in vivo the only or central cellular receptor for HTNV infection is not known. To investigate the role of β3 integrin for cellular entry of HTNV, we established an HTNV infection model in newborn murine pups. Infected pups died at an average age of 14.2 ± 1.1 days with high levels of viral antigen detected in their brain, lung, and kidney. Pre-injection of blocking monoclonal antibodies (mAb) specific for either β3 or αV prolonged survival significantly to a maximal average survival of 19.7 ± 1.5 days (P < 0.01) and 18.4 ± 0.9 days (P < 0.01), respectively. XT-199, a chemical blocker of the αVβ3 receptor also prolonged survival to 19.5 ± 1.3 days (P < 0.01). In contrast to these receptor blockades, anti-HTNV antibody was not only able to prolong survival, but 20% of infected pups achieved long-term survival. An anti-murine β1 antibody comparatively prolonged survival (19.0 ± 1.2 days), suggesting that HTNV infection is partly mediated through integrin β1 receptors as well as through β3 receptors in vivo. Our data demonstrate that the β3 receptor is important for HTNV infection in vivo, but also suggest that HTNV may utilize additional receptors beyond β3 for cellular entry within an organism.

KW - Hantaan virus

KW - Integrin β

KW - Integrin β

KW - Receptor

KW - Viral entry

UR - http://www.scopus.com/inward/record.url?scp=18744381021&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=18744381021&partnerID=8YFLogxK

M3 - Article

C2 - 15886525

AN - SCOPUS:18744381021

VL - 37

SP - 121

EP - 127

JO - Experimental and Molecular Medicine

JF - Experimental and Molecular Medicine

SN - 1226-3613

IS - 2

ER -