Ferraris Olivier, Kessler Nicole, Valette Martine, Lina Bruno
Laboratoire de Virologie, Centre National de Référence pour la Grippe (France-Sud), Domaine Rockefeller, 8 avenue Rockefeller, 69373 Lyon Cedex 08, France.
Vaccine. 2006 Nov 10;24(44-46):6656-9. doi: 10.1016/j.vaccine.2006.05.050. Epub 2006 Jun 8.
In 2002, prior to the generalization of zanamivir and oseltamivir utilization in France, we had decided to test a large panel of influenza strains to establish the baseline sensitivity of these viruses to anti-neuraminidase drugs. Since 2002, routine monitoring of resistance relies mainly on the results of neuraminidase enzyme assay. The profile of sensitivity of A/H3N2 viruses has not changed during these three influenza seasons. Neuraminidase N2 was shown to be more sensitive to oseltamivir carboxylate than to zanamivir. Amongst 788 viruses tested, only 10 were found with outliers IC(50) values (seven in 2003, one in 2004, and two in 2005). After the sequencing of the neuraminidase segment of these viruses, seven mutations on the stalk or the head of the glycoprotein (A18S, L23F, C42R, R143V, E199K, S332K, R431N) were detected. Moreover during seasons 2003-2005, 12 additional viruses were characterized by a complete lack of neuraminidase activity. In these viruses, viral resistance to NA inhibitors can be related with the presence of a defective neuraminidase RNA segment as evaluated by a plaque reduction assay, these viruses having a reduced dependence on its neuraminidase activity.
2002年，在法国推广扎那米韦和奥司他韦使用之前，我们决定对大量流感毒株进行检测，以确定这些病毒对抗神经氨酸酶药物的基线敏感性。自2002年以来，耐药性的常规监测主要依赖神经氨酸酶酶活性测定的结果。在这三个流感季节中，A/H3N2病毒的敏感性概况没有变化。神经氨酸酶N2对奥司他韦羧酸盐比对扎那米韦更敏感。在检测的788株病毒中，仅发现10株具有异常的IC(50)值（2003年7株，2004年1株，2005年2株）。对这些病毒的神经氨酸酶片段进行测序后，在糖蛋白的柄部或头部检测到7个突变（A18S、L23F、C42R、R143V、E199K、S332K、R431N）。此外，在2003 - 2005年流感季节期间，又有12株病毒表现为完全缺乏神经氨酸酶活性。在这些病毒中，通过蚀斑减少试验评估，病毒对神经氨酸酶抑制剂的耐药性可能与存在缺陷的神经氨酸酶RNA片段有关，这些病毒对其神经氨酸酶活性的依赖性降低。
