Schmidtke Michaela, Zell Roland, Bauer Katja, Krumbholz Andi, Schrader Christina, Suess Jochen, Wutzler Peter
Institute of Virology and Antiviral Therapy, Medical Centre of the Friedrich Schiller University Jena, Jena, Germany.
Intervirology. 2006;49(5):286-93. doi: 10.1159/000094244. Epub 2006 Jun 29.
This study was designed to gain insight into amantadine susceptibility of porcine influenza A viruses isolated in Germany between 1981 and 2001. The 12 studied H1N1, H1N2, and H3N2 porcine influenza virus strains were isolated in chicken eggs and passaged once in MDCK cells. Plaque reduction assays were applied to examine virus susceptibility to amantadine. Genotyping was used to confirm drug resistance. In the results of these antiviral studies, only 3 of the 12 isolates were shown to be amantadine-susceptible. All resistant strains contained the AA substitutions G16E, S31N, and R77Q in the membrane protein 2 (M2). Additionally, L27A was detected in two H1N1 strains. S31N and/or L27A are well-known amino acid substitutions in M2 that confer amantadine resistance. The role of the pig as an intermediate host of avian and human influenza A viruses, the possible involvement of genetic reassortment, and the high incidence of naturally amantadine-resistant porcine influenza A viruses suggest a real risk of emergence of amantadine resistant human viruses. Therefore, drug susceptibility monitoring appears to be warranted for effective application of those drugs.
本研究旨在深入了解1981年至2001年间在德国分离出的甲型猪流感病毒对金刚烷胺的敏感性。所研究的12株H1N1、H1N2和H3N2甲型猪流感病毒毒株在鸡胚中分离，并在MDCK细胞中传代一次。采用蚀斑减少试验检测病毒对金刚烷胺的敏感性。基因分型用于确认耐药性。在这些抗病毒研究结果中，12株分离株中只有3株对金刚烷胺敏感。所有耐药毒株在膜蛋白2（M2）中都含有氨基酸替换G16E、S31N和R77Q。此外，在两株H1N1毒株中检测到L27A。S31N和/或L27A是M2中已知的赋予金刚烷胺抗性的氨基酸替换。猪作为甲型禽流感病毒和人流感病毒中间宿主的作用、基因重配的可能参与以及天然金刚烷胺耐药甲型猪流感病毒的高发生率表明，出现金刚烷胺耐药人类病毒存在实际风险。因此，为有效应用这些药物，似乎有必要进行药物敏感性监测。
