Abstract
We tested the ability of retrocyclin 2, a type of θ defensin, to protect cells and chicken embryos from infection by H5N1 highly pathogenic avian influenza virus. A gene fragment of retrocyclin 2 was designed based on the protein sequence of retrocyclin 2 and cloned into the eukaryotic expression vector pcDNA4.01 (HismaxA), named pcDNA4-RC2. The expression vector pcDNA4-RC2 protected MDCK cells and chicken embryos from infection by the H5N1 virus through inhibition of virus replication and viral mRNA transcription. Retrocyclin 2 is therefore effective in preventing H5N1 virus infection in vivo and in vitro and could be considered as a new therapy for H5N1 influenza and other diseases.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Barry DG, Daly NL, Clark RJ et al (2003) Linearization of a naturally occurring circular protein maintains structure but eliminates hemolytic activity. Biochemistry 42:6688–6695
Cole AM, Hong T, Boo LM et al (2002) Retrocyclin: a primate peptide that protects cells from infection by T- and M-tropic strains of HIV-1. Proc Natl Acad Sci USA 99:1813–1818
Craik DJ, Daly NL, Saska I et al (2003) Structures of naturally occurring circular proteins from bacteria. J Bacteriol 185:4011–4021
Doss M, White MR, Tecle T et al (2009) Interactions of α-, β-, and θ-defensins with Influenza A virus and surfactant protein D. J Immunol 182:7878–7887
Ge Q, McManus M, Nguyen T et al (2003) RNA interference of influenza virus production by directly targeting mRNA for degradation and indirectly inhibiting all viralRNA transcription. Proc Natl Acad Sci USA 100:2718–2723
Kim C, Gajendran N, Mittrucker H et al (2005) Human α-defensins neutralize anthrax lethal toxin and protect against its fatal consequences. Proc Natl Acad Sci USA 102:4830–4835
Munk C, Wei G, Yang OO et al (2003) The theta-defensin, retrocyclin, inhibits HIV-1 entry. AIDS Res Hum Retrovir 19:875–881
Nguyen TX, Cole AM, Lehrer RI (2003) Evolution of primate θ-defensins: a serpentine path to a sweet tooth. Peptides 24:1647–1654
Rosengren KJ, Daly NL, Plan MR et al (2003) Twists, knots, and rings in proteins. Structural definition of the cyclotide framework. J Biol Chem 278:8606–8616
Tang YQ, Yuan J, Osapay G et al (1999) A cyclic antimicrobial peptide produced in primate leukocytes by the ligation of two truncated alpha-defensins. Science 286:498–502
Trabi M, Schirra HJ, Craik DJ (2001) Three-dimensional structure of RTD-1, a cyclic antimicrobial defensin from rhesus macaque leukocytes. Biochemistry 40:4211–4221
Wang W, Cole AM, Hong T et al (2003) Retrocyclin, an antiretroviral theta-defensin, is a lectin. J Immunol 170:4708–4716
WHO (2009) Cumulative number of confirmed human cases of avian influenza A/(H5N1) reported to WHO. http://www.who.int/csr/disease/avian_influenza/country/cases_table_2009_06_02/en/index.html
Yasin B, Wang W, Pang M et al (2004) θ Defensins protect cells from infection by herpes simplex virus by inhibiting viral adhesion and entry. J Virol 78:5147–5156
Acknowledgments
The study was supported by grants from CAS Innovation Program (KSCX2-YW-N-063), Hi-Tech Research and development program of China (863program) (2007AA100606), National Key Basic Research and Development Program of China (9732007BC109103), USDA and IDRC.
Author information
Authors and Affiliations
Corresponding author
Additional information
Qing-long Liang and Kai Zhou are co-first authors.
Rights and permissions
About this article
Cite this article
Liang, Ql., Zhou, K. & He, Hx. Retrocyclin 2: a new therapy against avian influenza H5N1 virus in vivo and vitro. Biotechnol Lett 32, 387–392 (2010). https://doi.org/10.1007/s10529-009-0167-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10529-009-0167-2