Influenza Virus Protecting RNA: an Effective Prophylactic and Therapeutic Antiviral

Dimmock, N. J. et al., J. Virol, 2008, 82: 8570-8578

Speaker: 李婉綺                                                   Time: 15:10-16:00, 29, Oct., 2008

Commentator: 陳舜華 老師                                Place: Room 601

Abstract:

      Infection with human influenza A virus can reach cataclysmic levels, with 40 or more ore million deaths arising from the 1918 pandemic. Currently, measures to counter human influenza include administration of killed and live vaccines and the antivirals oseltamivir (Tamiflu) and zanamivir (Relenza). However, antigenic drift of influenza viral surface is altered within 4 years on average, which can evade previously acquired immunity (1). Viral resistance to oseltamivir has already been recorded in human virus isolates and is causing concern. A new measures to combat this and seasonal influenza are urgently needed (2, 3). In this study (4), a new concept in antivirals based on a defined, naturally occurring defective influenza virus RNA that has the potential to protect against any influenza A virus in any animal host (5). This “protecting RNA” (244 RNA) is incorporated into virions which, although noninfectious, deliver the RNA to the respiratory cells are naturally infected by influenza virus. The 224 protecting virus protected mice against a simultaneous challenge of lethal doses of influenza A/WSN (H1N1) virus, and doses as well as H2N2, H3N2 and H3N8. The 244 virus was 10- to 100-fold more active than previously characterized defective influenza A viruses, and the protecting activity was confirmed to reside in the 244 RNA molecule by recovering a protecting virus entirely from cloned cDNA. In addition, when the 244 virus was administered 24 to 48 h after a lethal challenge, it provided a clear therapeutic benefit which has not been previously observed with any defective virus.

References:

1.      Mann, A., A. C. Marriott, S. Balasingam, R. Lambkin, J. S. Oxford, and N. J. Dimmock. 2006. Interfering vaccine (defective interfering influenza A virus) protects ferrets from influenza, and allows them to develop solid immunity to reinfection. Vaccine 24:4290-4296.

2.      Hayden, F. G. 2006. Antiviral resistance in influenza viruses—implications for management and pandemic response. N. Engl. J. Med. 354:785–788.

3.      Le, Q. L., M. Kiso, K. Someya, Y. Sakai, N. D. Nguyen, K. L. H. Nguyen, N. D. Pham, H. H. Ngyen, S. Yamada, Y. Muramoto, T. Horimoto, A. Takada, H. Goto, T. Suzuki, Y. Suzuki, and Y. Kawaoka. 2005. Isolation of drug-resistant H5N1 virus. Nature 437:1108.

4.      Nigel J. Dimmock, Edward W. Rainsford, Paul D. Scott, and Anthony C. Marriott. 2008.  Influenza Virus Protecting RNA: an Effective Prophylactic and Therapeutic Antiviral. J. Virol 82:857

5.      Huang, A. S., and D. Baltimore. 1970. Defective viral particles and viral disease processes. Nature (London) 226:325–327.