Mutations in VP1 and 3A proteins improve binding and replication of rhinovirus C15 in HeLa-E8 cells

作者：Bochkov Yury A^*; Watters Kelly; Basnet Sarmila; Sijapati Shakher; Hill Marchel; Palmenberg Ann C; Gern James E

来源：Virology, 2016, 499: 350-360.

DOI：10.1016/j.virol.2016.09.025

• Rhinovirus C
• Pathogenesis
• Adaptation
• Receptor specificity
• Heparan sulfate

Viruses in the rhinovirus C species (RV-C) can cause severe respiratory illnesses in children including pneumonia and asthma exacerbations. A transduced cell line (HeLa-E8) stably expressing the CDHR3-Y-529 receptor variant, supports propagation of RV-C after infection. C15 clinical or recombinant isolates replicate in HeLa-E8, however progeny yields are lower than those of related strains of RV-A and RV-B. Serial passaging of C15 in HeLa-E8 resulted in stronger cytopathic effects and increased (>= 10-fold) virus binding to cells and progeny yields. The adaptation was acquired by two mutations which increased binding (VP1 T125K) and replication (3A E41K), respectively. A similar 3A mutation engineered into C2 and C41 cDNAs also improved viral replication (2-8 fold) in HeLa but the heparan sulfate mediated cell-binding enhancement by the VP1 change was C15-specific. The findings now enable large-scale cost-effective C15 production by infection and the testing of RV-C infectivity by plaque assay.

• 出版日期2016-12