Analysis of the integrin β₃ receptor for pathogenic orthohantaviruses in rodent host species

Host reservoir specificity of pathogens is complex and may depend on receptor variability. For pathogenic orthohantaviruses, integrin β₃ had been previously identified as entry receptor and the presence of aspartic acid residue at position 39 (D39) in human integrin β₃ was described to be a prerequisite for infection of primate cells with Hantaan virus (HTNV). However, the role of integrin β₃ in orthohantavirus infection of host animals is not completely understood. Therefore, we analyzed the nucleotide sequence of the integrin β₃ gene of Myodes glareolus and Apodemus agrarius, the hosts of Puumala virus (PUUV) and HTNV, respectively. Sequence analysis in tissue samples demonstrated that the amino acid residue D39 is not present in integrin β₃ of these natural orthohantavirus hosts. Furthermore, we analyzed the transcription and protein expression levels of integrin β₃ in the renal cell line BVK168 generated from the PUUV host, bank vole. Transcription level of integrin β₃ was 100-fold lower in BVK168 cells than in Vero E6 cells and integrin β₃ expression was not detectable in BVK168 cells. However, despite the absence of amino acid residue D39 and no detectable integrin β₃ expression, BVK168 cells are susceptible to infection with both PUUV and HTNV. These results indicate that the mechanism of orthohantaviral entry in rodent species does not correspond to the requirements that were described for the entry in primate cells in vitro.