Laboratory of Immunoregulation, US Food and Drug Administration, 29 Lincoln Drive, Bethesda, MD 20892, USA.
Virology. 2010 Nov 25;407(2):374-80. doi: 10.1016/j.virol.2010.08.027. Epub 2010 Sep 24.
The 2009 H1N1 pandemic highlights the need to better understand influenza A infectivity and antigenicity. Relative to other recent seasonal H1N1 influenza strains, the 2009 H1N1 virus grew less efficiently in eggs, which hindered efforts to rapidly supply vaccine. Using lentiviral pseudotypes bearing influenza hemagglutinin (HA-pseudotypes) we evaluated a glutamine to arginine mutation at position 223 (Q223R) and glycosylation at residue 276 in HA for their effects on infectivity and neutralization. Q223R emerged during propagation in eggs and lies in the receptor binding site. We found that the Q223R mutation greatly enhanced infectivity of HA-pseudotypes in human cells, which was further augmented by inclusion of the viral neuraminidase (NA) and M2 proteins. Loss of glycosylation at residue 276 did not alter infectivity. None of these modifications affected neutralization. These findings provide information for increasing 2009 H1N1HA-pseudotype titers without altering antigenicity and offer insights into receptor use.
2009 年 H1N1 大流行凸显了更好地了解甲型流感传染性和抗原性的必要性。与其他最近的季节性 H1N1 流感株相比，2009 年 H1N1 病毒在鸡蛋中的生长效率较低，这阻碍了快速供应疫苗的努力。我们使用带有流感血凝素（HA-假型）的慢病毒假型来评估 HA 位置 223 处的谷氨酰胺到精氨酸突变（Q223R）和 276 位的糖基化对感染性和中和作用的影响。Q223R 在鸡蛋中繁殖时出现，位于受体结合位点。我们发现，Q223R 突变极大地增强了 HA-假型在人细胞中的感染性，而包含病毒神经氨酸酶（NA）和 M2 蛋白则进一步增强了感染性。残基 276 处糖基化的丧失不会改变感染性。这些修饰都不影响中和作用。这些发现提供了在不改变抗原性的情况下提高 2009 年 H1N1HA-假型效价的信息，并为受体利用提供了深入了解。
