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SHVRI, CAAS Finds that Nucleolin Plays a Key Role in RHDV Internalization

Source: Shanghai Veterinary Research Institute

2018-11-07 10:15

Recently, the Small Animal Infectious Disease team from Shanghai Veterinary Research Institute (SHVRI) of Chinese Academy of Agricultural Sciences (CAAS) found that nucleolin (NCL) mediates the internalization of Rabbit hemorrhagic disease virus (RHDV) through clathrin-dependent endocytosis. The results have been published in PLoS Pathogens with Dr. Zhu Jie as the first author and Prof. Liu Guangqing as the corresponding author, who is the chief of Small Animals Infectious Disease Team of SHVRI.

RHDV is an important member of the Caliciviridae family and a highly lethal pathogen in rabbits. Although the cell receptor of RHDV has been identified, the mechanism underlying RHDV internalization remains unknown. The researchers have demonstrated that NCL efficiently mediates RHDV internalization by interacting with the RHDV capsid protein (VP60). The exact function domains of the interaction between NCL and VP60 were also determined. Notably, these functional domains are highly conserved in all RHDV genotypes. Further, the researchers revealed that NCL was involved in clathrin-dependent endocytosis through interactions with the C-terminal residues of clathrin light chain A. In addition, the researchers found that the artificial peptide (DVN peptide) based on the functional domain, which is responsible for RHDV VP60 binding to NCL, is able to inhibit RHDV infection, which indicates that the DVN peptide might be a candidate target for the design of antiviral drugs against RHDV infection.

This study was supported by grants from the National Natural Science Foundation of China (Grant No.: 31672572), the Key Project of Agriculture Science and Technology of Shanghai (Grant No.: 2016043), the Foundation of Shanghai Key Laboratory of Veterinary Biotechnology (Grant No.: klab201712) and the National Key Research and Development Program of China (Grant No.: 2016YFD0500108).

More details are available on the bellow links: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007383

By Zhu Jie

Fig 1. NCL is involved in RHDV internalization

Fig 2. The P1s domain of the RHDV VP60 protein contains a conserved sequence motif that binds to the NCL NTD domain

Fig 3. RHDV internalization model