Exp Mol Med.  2005 Apr;37(2):121-127.

In vivo characterization of the integrin beta3 as a receptor for Hantaan virus cellular entry

• Song JW
• Song KJ
• Baek LJ
• Frost B
• Poncz M
• Park KS

Abstract

Binding of viruses to cell surface molecules is an essential step in viral infection. In vitro studies suggested that the alpha v beta3 integrin receptor is the epithelial cell receptor for Hantaan virus (HTNV). Whether beta3 is in vivo the only or central cellular receptor for HTNV infection is not known. To investigate the role of beta3 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 beta3 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 beta3 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 beta1 antibody comparatively prolonged survival (19.0 +/- 1.2 days), suggesting that HTNV infection is partly mediated through integrin beta1 receptors as well as through beta3 receptors in vivo. Our data demonstrate that the beta3 receptor is important for HTNV infection in vivo, but also suggest that HTNV may utilize additional receptors beyond beta3 for cellular entry within an organism.

Keyword

Hantaan virus; integrin beta3; integrin beta1; receptor; viral entry

MeSH Terms

Animals
Animals, Newborn
Antibodies, Monoclonal/therapeutic use
Antigens, CD29/metabolism
Hantaan virus/*metabolism/pathogenicity
Hemorrhagic Fever with Renal Syndrome/mortality/*virology
Imidazoles/pharmacology
Integrin alphaV/metabolism
Integrin alphaVbeta3/antagonists & inhibitors
Integrin beta3/*metabolism
Mice
Receptors, Virus/*metabolism
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.