CHARACTERISATION OF INFLUENZA A (H1N1 AND H7N7) VARIANTS RESISTANT TO COMMERCIAL ANTIVIRAL DRUGS
Main Article Content
Authors
I.S. Korotetskiy
Scientific Centre for Anti-infectious Drugs, 84, Auezov srt. Almaty, Kazakhstan
N.V. Zubenko
Scientific Centre for Anti-infectious Drugs, 84, Auezov srt. Almaty, Kazakhstan
S.V. Shilov
Scientific Centre for Anti-infectious Drugs, 84, Auezov srt. Almaty, Kazakhstan
L.N. Ivanova
Scientific Centre for Anti-infectious Drugs, 84, Auezov srt. Almaty, Kazakhstan
S.V. Shvidko
Scientific Centre for Anti-infectious Drugs, 84, Auezov srt. Almaty, Kazakhstan
R.D. Toxanbayev
Scientific Centre for Anti-infectious Drugs, 84, Auezov srt. Almaty, Kazakhstan
Abstract
Here, we describe the adaptation of influenza strains A/FPV/Weybridge/78 (H7N7) and A/Swine/Iowa/30 (H1N1) to the derivatives of adamantane (Rimantadine) and the neuraminidase inhibitor (Tamiflu). To determine the stability of the resistance phenotype, mutant strains were consecutively passaged in the absence of antiviral drugs for 5 passages. The IC50 value for FPV_RTam and Sw_RTam was >0.3 mg/ml for Tamiflu and >0.1 mg/ml for Rimantadine, respectively. Furthermore, the thermal stability of haemagglutinin and neuraminidase activity was determined in the study. Analysis of the amino acid sequence revealed the presence of a S31N substitution in the M2 protein of the FPV_RRim mutant strain, and an A30T substitution in Sw_RRim, which is responsible for the development of Rimantadine resistance. A specific substitution in position N207S of the amino acid sequences of the M1 protein in FPV_RTam and Sw_RTam mutants was also observed. Taken together, the results suggest that the nature of drug resistance is a multigene character.
Keywords
influenza virus, drug resistance, Tamiflu, Rimantadine, sequencing, mutation
Article Details
References
Rotanov M. Kontrol' chuvstvitel'nosti shtammov virusa grippa A k protivovirusnym lekarstvennym sredstvam: avtoref. … kand. biol. nauk: 15.00.02. M., 2008, 133 s. – 003171132.
Choung U.K., Xiaowu Ch., Dirk B.M. Neuraminidase inhibitors as anti-influenza virus agents. Antiviral Chemistry and Chemotherapy, 1999, vol. 10, рр. 141-154. PMID: 10480735.
Brandi M.B., Slavish P.J., DuBois R.M., Boyd V.A., White S.W., Webb T.R. Identification of influenza endonuclease inhibitors using a novel fluorescence polarization assay. ACS Chem. Biol., 2012, vol. 7, no. 3, рр. 526-534. DOI: 10.1021/cb200439z.
Leneva I.A., Gus'kova T.A. Arbidol – jeffektivnyj preparat dlja lechenija i profilaktiki grippa i ORVI: obzor rezul'tatov klinicheskih issledovanij. Russkij medicinskij zhurnal: nezavisimoe izdanie dlja praktikujushhih vrachej, 2008, vol. 16, no. 29, ss. 3-9.
Pontoriero A., Baumeister E., Campos A.M., Savy V.L. Virological surveillance and antiviral resistance of human influenza virus in Argentina, 2005 – 2008. Rev Panam Salud Publica, 2011, vol. 30, no. 6, pp. 634-640. DOI: 10.1590/S1020-49892011001200023.
Smirnov V.S., Profilaktika i lechenie grippa i ostryh respiratornyh virusnyh infekcij. Ruk. dlja terapevtov, infekcionistov, semejnyh vrachej – SPb: AJSING, 2012, 56 s.
Kinchington D. Recent advances in antiviral therapy. J. Clin. Pathol., 1999, vol. 52, no. 2, pp. 89-94. DOI: 10.1136/jcp.52.2.89.
Chernova T.M., Timchenko V.N. Protivovirusnye preparaty i lechenie grippa. Vserossijskij mezhdisciplinarnyj medicinskij zhurnal, 2011, vol. 64, no. 1, ss. 10-14.
Bright R.A., Medina M.J., Xu X., Perez-Oronoz G., Wallis T.R., Davis X.M., Povinelli L., Cox N.J., Klimov A.I. Incidence of adamantane resistance among influenza A (H3N2) viruses isolated worldwide from 1994 to 2005: a cause for concern. Lancet, 2005, vol. 366, no. 9492, pp. 1175-1181. DOI: Crossref.
Ziegler T., Hemphill M.L., Ziegler M., Perez-Oronoz G., Klimov A.I., Hampson A.W., Regnery H.L., Cox N.J. Low Incidence of Rimantadine Resistance in Field Isolates of Influenza A Viruses. J. Infect. Dis., 1999, vol. 180, no. 4, pp. 935-939. DOI: 10.1086/314994.
Yi M., Cross T.A., Zhou H.-X. Conformational heterogeneity of the M2 proton channel and a structural model for channel activation. Proc. Natl. Acad. Sci. USA, 2009, vol. 106, no. 32, pp. 13311-13316. DOI: 10.1073/pnas.0906553106.
Wang J.-F., Wei D.-Q., Chou K.-C. Insights from investigating the interactions of adamantane–based drugs with the M2 proton channel from the H1N1 swine virus. Biochem. Biophys. Res. Commun., 2009, vol. 388, no. 2, pp. 413-417. DOI: 10.1016/j.bbrc.2009.08.026.
Silujanova Je.V. Jevoljucionnaja izmenchivost' virusov grippa A(H3N2) i V v period 2003-2013 gg. v RF: avtoref. … kand. biol. nauk: 03.02.02, 03.01.03. M., 2014, 167 s.
Erofeeva M.K., Pozdnjakova M.G., Maksakova V.L. Aktual'nye voprosy profilaktiki grippa i drugih ORVI. Russkij medicinskij zhurnal: nezavisimoe izdanie dlja praktikujushhih vrachej, 2011, vol. 19, ss. 2091-2095.
Szretter K.J., Balish A.L., Katz J.M. Current Protocols in Microbiology – 2006. – Unit. 15G.1 – 15G.1.22: Influenza: Propagation, quantification, and storage.
Reed L., Muench H. A simple method of estimating fifty percent endpoints. Amer. J. Hyg., 1938, vol. 27, pp. 493-497.
Zubenko N.V., Koroteckij I.S., Shilov S.V., Ivanova L.N. Adaptacija shtammov virusa grippa s razlichnoj antigennoj strukturoj k kommercheskim antivirusnym preparatam. I Mezhdunarodnaja konferencija molodyh uchenyh: biotehnologov, molekuljarnyh biologov i virusologov. Novosibirsk, 2014, ss. 41-45.
Barnett J.M., Cadman A., Burrell F.M., Madar S.H., Lewis A.P., Tisdale M., Bethell R. In Vitro selection and characterisation of influenza B/Beijing/1/87 isolates with altered susceptibility to zanamivir. Virology, 1999, vol. 265, no. 2, pp. 286-295. DOI: 10.1006/viro.1999.0058.
Aminoff D. Method for the quantitative estimation of N-acetylneuraminic acid and their application to hydrolysates of sialomucoids. Biochem. J., 1961, vol. 81, pp. 384-392. PMID: 13860975.
Carr C.M., Chaudhry C., Kim, P.S. Influenza hemagglutinin is spring-loaded by a metastable native conformation. Proc. Natl. Acad. Sci. USA, 1997, vol. 94, pp. 14306-14313. PMID: 9405608.