Abstract
Amantadine (1-aminoadamantane hydrochloride) is effective in the prophylaxis and treatment of influenza A infections. In tissue culture this selective, strain-specific antiviral activity occurs at relatively low concentrations (5 microM or less), which inhibit either the initiation of infection or virus assembly. The data reported here demonstrate that the basis of these actions is similar and resides in the virus-coded M2 membrane protein, the product of a spliced transcript of RNA segment 7. Mutations which confer resistance to amantadine are restricted to four amino acids within a hydrophobic sequence, indicating that the drug is targetted against the putative membrane-associated portion of the molecule. The influence of the virus haemagglutinin on the amantadine sensitivity of virus strains implies that the drug may interfere with interactions between these two virus proteins.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Appleyard G. Amantadine-resistance as a genetic marker for influenza viruses. J Gen Virol. 1977 Aug;36(2):249–255. doi: 10.1099/0022-1317-36-2-249. [DOI] [PubMed] [Google Scholar]
- Appleyard G., Maber H. B. A plaque assay for the study of influenza virus inhibitors. J Antimicrob Chemother. 1975 Dec;1(4 Suppl):49–53. doi: 10.1093/jac/1.suppl_4.49. [DOI] [PubMed] [Google Scholar]
- Daniels R. S., Downie J. C., Hay A. J., Knossow M., Skehel J. J., Wang M. L., Wiley D. C. Fusion mutants of the influenza virus hemagglutinin glycoprotein. Cell. 1985 Feb;40(2):431–439. doi: 10.1016/0092-8674(85)90157-6. [DOI] [PubMed] [Google Scholar]
- Dolin R., Reichman R. C., Madore H. P., Maynard R., Linton P. N., Webber-Jones J. A controlled trial of amantadine and rimantadine in the prophylaxis of influenza A infection. N Engl J Med. 1982 Sep 2;307(10):580–584. doi: 10.1056/NEJM198209023071002. [DOI] [PubMed] [Google Scholar]
- Hay A. J., Kennedy N. C., Skehel J. J., Appleyard G. The matrix protein gene determines amantadine-sensitivity of influenza viruses. J Gen Virol. 1979 Jan;42(1):189–191. doi: 10.1099/0022-1317-42-1-189. [DOI] [PubMed] [Google Scholar]
- Hay A. J. Studies on the formation of the influenza virus envelope. Virology. 1974 Aug;60(2):398–418. doi: 10.1016/0042-6822(74)90335-3. [DOI] [PubMed] [Google Scholar]
- Helenius A., Kartenbeck J., Simons K., Fries E. On the entry of Semliki forest virus into BHK-21 cells. J Cell Biol. 1980 Feb;84(2):404–420. doi: 10.1083/jcb.84.2.404. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Helenius A., Marsh M., White J. Inhibition of Semliki forest virus penetration by lysosomotropic weak bases. J Gen Virol. 1982 Jan;58(Pt 1):47–61. doi: 10.1099/0022-1317-58-1-47. [DOI] [PubMed] [Google Scholar]
- Lamb R. A., Lai C. J., Choppin P. W. Sequences of mRNAs derived from genome RNA segment 7 of influenza virus: colinear and interrupted mRNAs code for overlapping proteins. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4170–4174. doi: 10.1073/pnas.78.7.4170. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lamb R. A., Zebedee S. L., Richardson C. D. Influenza virus M2 protein is an integral membrane protein expressed on the infected-cell surface. Cell. 1985 Mar;40(3):627–633. doi: 10.1016/0092-8674(85)90211-9. [DOI] [PubMed] [Google Scholar]
- Lubeck M. D., Schulman J. L., Palese P. Susceptibility of influenza A viruses to amantadine is influenced by the gene coding for M protein. J Virol. 1978 Dec;28(3):710–716. doi: 10.1128/jvi.28.3.710-716.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McCauley J. W., Mahy B. W., Inglis S. C. Nucleotide sequence of fowl plague virus RNA segment 7. J Gen Virol. 1982 Jan;58(Pt 1):211–215. doi: 10.1099/0022-1317-58-1-211. [DOI] [PubMed] [Google Scholar]
- Ortín J., Martínez C., del Río L., Dávila M., López-Galíndez C., Villanueva N., Domingo E. Evolution of the nucleotide sequence of influenza virus RNA segment 7 during drift of the H3N2 subtype. Gene. 1983 Aug;23(2):233–239. doi: 10.1016/0378-1119(83)90055-0. [DOI] [PubMed] [Google Scholar]
- Oxford J. S., Galbraith A. Antiviral activity of amantadine: a review of laboratory and clinical data. Pharmacol Ther. 1980;11(1):181–262. doi: 10.1016/0163-7258(80)90072-8. [DOI] [PubMed] [Google Scholar]
- PORTERFIELD J. S. A simple plaque-inhibition test for the study of arthropod-borne viruses. Bull World Health Organ. 1960;22:373–380. [PMC free article] [PubMed] [Google Scholar]
- Patel T. P., Millican T. A., Bose C. C., Titmas R. C., Mock G. A., Eaton M. A. Improvements to solid phase phosphotriester synthesis of deoxyoligonucleotides. Nucleic Acids Res. 1982 Sep 25;10(18):5605–5620. doi: 10.1093/nar/10.18.5605. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Porter A. G., Barber C., Carey N. H., Hallewell R. A., Threlfall G., Emtage J. S. Complete nucleotide sequence of an influenza virus haemagglutinin gene from cloned DNA. Nature. 1979 Nov 29;282(5738):471–477. doi: 10.1038/282471a0. [DOI] [PubMed] [Google Scholar]
- Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schiffer M., Edmundson A. B. Use of helical wheels to represent the structures of proteins and to identify segments with helical potential. Biophys J. 1967 Mar;7(2):121–135. doi: 10.1016/S0006-3495(67)86579-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Scholtissek C., Faulkner G. P. Amantadine-resistant and -sensitive influenza A strains and recombinants. J Gen Virol. 1979 Sep;44(3):807–815. doi: 10.1099/0022-1317-44-3-807. [DOI] [PubMed] [Google Scholar]
- Skehel J. J., Hay A. J., Armstrong J. A. On the mechanism of inhibition of influenza virus replication by amantadine hydrochloride. J Gen Virol. 1978 Jan;38(1):97–110. doi: 10.1099/0022-1317-38-1-97. [DOI] [PubMed] [Google Scholar]
- Wallbank A. M., Matter R. E., Klinikowski N. G. 1-Adamantanamine hydrochloride: inhibition of Rous and Esh Sarcoma viruses in cell culture. Science. 1966 Jun 24;152(3730):1760–1761. doi: 10.1126/science.152.3730.1760. [DOI] [PubMed] [Google Scholar]
- Winter G., Fields S. Cloning of influenza cDNA ino M13: the sequence of the RNA segment encoding the A/PR/8/34 matrix protein. Nucleic Acids Res. 1980 May 10;8(9):1965–1974. doi: 10.1093/nar/8.9.1965. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yoshimura A., Kuroda K., Kawasaki K., Yamashina S., Maeda T., Ohnishi S. Infectious cell entry mechanism of influenza virus. J Virol. 1982 Jul;43(1):284–293. doi: 10.1128/jvi.43.1.284-293.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]