In vivo characterization of the integrin beta3 as a receptor for Hantaan virus cellular entry.
Binding of viruses to cell surface molecules is an essential step in viral infection. In vitro studies suggested that the alpha(v)beta(3) integrin receptor is the epithelial cell receptor for Hantaan virus (HTNV). Whether beta(3) is in vivo the only or central cellular receptor for HTNV infection is not known. To investigate the role of beta(3) 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 beta(3) or av 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 alpha(v)beta(3) 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 beta(1) antibody comparatively prolonged survival (19.0 +/- 1.2 days), suggesting that HTNV infection is partly mediated through integrin beta(1) receptors as well as through beta(3) receptors in vivo. Our data demonstrate that the beta(3) receptor is important for HTNV infection in vivo, but also suggest that HTNV may utilize additional receptors beyond beta(3) for cellular entry within an organism.
Song
Jin-Won
JW
Department of Microbiology and the Institute for Viral Diseases, Division of Brain Korea 21 Program for Biomedical Science, College of Medicine Korea University, Seoul 136-705, Korea.
Song
Ki-Joon
KJ
Baek
Luck-Ju
LJ
Frost
Blasie
B
Poncz
Mortimer
M
Park
KwangSook
K
D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D018063:Hantaan virus / Q000378:metabolism* / Q000472:pathogenicity; D006480:Hemorrhagic Fever with Renal Syndrome / Q000401:mortality / Q000821:virology*; D007093:Imidazoles / Q000494:pharmacology; D039564:Integrin alphaV / Q000378:metabolism; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors; D019012:Integrin beta1 / Q000378:metabolism; D039661:Integrin beta3 / Q000378:metabolism*; D051379:Mice; D011991:Receptors, Virus / Q000378:metabolism*
C426703:3-(3-(3-(4,5-dihydroimidazol-2-ylamino)propyloxylisoxazol-5-yl)carbonylamino)-2-(phenylsulfonylamino)propionic acid; D000911:Antibodies, Monoclonal; D007093:Imidazoles; D039564:Integrin alphaV; D039302:Integrin alphaVbeta3; D019012:Integrin beta1; D039661:Integrin beta3; D011991:Receptors, Virus