Targeted inhibition of Hantavirus replication and intracranial pathogenesis by a chimeric protein-delivered siRNA.

Targeted inhibition of Hantavirus replication and intracranial pathogenesis by a chimeric protein-delivered siRNA. Antiviral Res. 2017 Oct 07;: Authors: Yang J, Sun JF, Wang TT, Guo XH, Wei JX, Jia LT, Yang AG Abstract Hantavirus (HV) infection, which underlies hantavirus hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome, remains to be a severe clinical challenge. Here, we synthesized small interfering RNAs (siRNAs) that target the encoding sequences of HV strain 76-118, and validated their inhibitory role in virus replication in HV-infected monkey kidney Vero E6 cells. A chimeric protein, 3G1-Cκ-tP, consisting of a single-chain antibody fragment (3G1) against the HV surface envelop glycoprotein, the constant region of human immunoglobulin κ chain (Cκ), and truncated protamine (amino acids 8-29, tP), was further generated. The fusion protein showed high affinity to HV antigen on the infected cell membrane, and internalized through clathrin-mediated endocytosis; it bound to siRNAs via the basic nucleic acid-rich protamine fragment, leading to their specific delivery into HV-infected cells and efficient inhibition of virus replication. An encephalitis mouse model was established via intracranial HV administration. Intraperitoneal injection of siRNAs complexed with 3G1-Cκ-tP achieved specific distribution of siRNAs in HV-infected brain cells, significantly reduced HV antigen levels, and effective protection fro...
Source: Antiviral Research - Category: Virology Authors: Tags: Antiviral Res Source Type: research