Cellular entry of Hantaan virus A9 strain: specific interactions with beta3 integrins and a novel 70kDa protein.
Cellular entry of pathogenic hantaviruses had been shown to be mediated by beta3 integrins. However, no direct evidence exists that hantavirus binds to beta3 integrins, and integrin beta3 subunit is not expressed on some cells permissive to hantavirus infection. In this report, utilizing beta3-integrin-transfected CHO cells, we demonstrated that integrin beta3 subunit renders CHO cells susceptible to Chinese Hantaan virus (HTN) strain A9 (isolated in China), and the viral infection was correspondingly inhibited by antibodies to alphavbeta3, alphaIIbbeta3, beta3, and alphav integrins. Furthermore, virus overlay protein-binding assay and 'quarternary Western' analysis indicate that HTN A9 directly interacts with beta3 integrins and an unidentified 70kDa protein. These findings indicate that beta3 integrins play a crucial role in cellular entry of HTN A9 via specific interactions with the virus. In addition, a novel 70kDa protein may serves as a candidate receptor or alternative cellular component for interaction with HTN.
Mou
Dan Lei
DL
Center of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China.
Wang
Ying Peng
YP
Huang
Chang Xing
CX
Li
Guang Yu
GY
Pan
Lei
L
Yang
Wei Song
WS
Bai
Xue Fan
XF
D000818:Animals; D000906:Antibodies / Q000276:immunology; D016466:CHO Cells; D006224:Cricetinae; D018063:Hantaan virus / Q000502:physiology*; D039661:Integrin beta3 / Q000276:immunology / Q000378:metabolism*; D008970:Molecular Weight; D011485:Protein Binding; D011991:Receptors, Virus / Q000737:chemistry* / Q000378:metabolism*; D013379:Substrate Specificity; D014162:Transfection
D000906:Antibodies; D039661:Integrin beta3; D011991:Receptors, Virus