Recombinant protein of heptad-repeat HR212, a stable fusion inhibitor with potent anti-HIV action in vitro
- Center for Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101 (China)
- Laboratory of Molecular Immunopharmacology, Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223 (China)
HR212, a recombinant protein expressed in Escherichia coli, has been previously reported to inhibit HIV-1 membrane fusion at low nanomolar level. Here we report that HR212 is effective in blocking laboratory strain HIV-1{sub IIIB} entry and replication with EC{sub 50} values of 3.92 {+-} 0.62 and 6.59 {+-} 1.74 nM, respectively, and inhibiting infection by clinic isolate HIV-1{sub KM018} with EC{sub 50} values of 44.44 {+-} 10.20 nM, as well as suppressing HIV-1-induced cytopathic effect with an EC{sub 50} value of 3.04 {+-} 1.20 nM. It also inhibited HIV-2{sub ROD} and HIV-2{sub CBL-20} entry and replication in the {mu}M range. Notably, HR212 was highly effective against T20-resistant strains with EC{sub 50} values ranging from 5.09 to 7.75 nM. Unlike T20, HR212 showed stability sufficient to inhibit syncytia formation in a time-of-addition assay, and was insensitive to proteinase K digestion. These results suggest that HR212 has great potential to be further developed as novel HIV-1 fusion inhibitor for treatment of HIV/AIDS patients, particularly for those infected by T20-resistant variants.
- OSTI ID:
- 21141012
- Journal Information:
- Virology, Vol. 377, Issue 1; Other Information: DOI: 10.1016/j.virol.2008.04.013; PII: S0042-6822(08)00253-5; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0042-6822
- Country of Publication:
- United States
- Language:
- English
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