Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, New Territories, Hong Kong SAR, China.
J Clin Virol. 2011 Apr;50(4):320-4. doi: 10.1016/j.jcv.2011.01.013. Epub 2011 Feb 16.
Aspartic acid to glycine substitution (D222G) of haemagglutinin subunit (HA1) was associated with adverse outcomes in 2009 pandemic influenza A (H1N1) infections.
To characterize the virological profile and antiviral response of patients infected with the HA1 D222G mutant.
Sixty-three adults admitted for pandemic influenza in Hong Kong were tested for D222G mutation by direct sequencing. Nasopharyngeal viral concentration on presentation was measured by real-time PCR to evaluate shedding from the upper respiratory tract. Serial upper and lower respiratory tract specimens were monitored to determine preferential tropism and document virological response to treatment.
The frequency of D222G infection was 17.4% among cases with severe pneumonia, and 26.7% among cases requiring intensive care. Altogether, four sporadic D222G cases spread across the first and second waves in Hong Kong were detected. A significant association between D222G infection with severe pneumonia (100% vs. 32.2%, P=0.015) and intensive care admission (100% vs. 18.6%, P=0.002) was observed. D222G was associated with lower concentrations of virus in the upper respiratory tract compared to wildtype, but persisted in the lower respiratory tract at high concentrations, despite clearance from the upper respiratory tract following antiviral treatment.
These observations suggest that D222G can arise de novo, sheds less virus from the upper respiratory tract and may be less transmissible, but more pneumotropic and more resistant to antiviral treatment. D222G is associated with a higher chance of developing critical disease. Lower respiratory tract specimen is needed for a reliable detection of this mutant.
血凝素亚单位（HA1）中的天门冬氨酸到甘氨酸取代（D222G）与 2009 年大流行性流感 A（H1N1）感染的不良结局相关。
描述感染具有 HA1 D222G 突变的患者的病毒学特征和抗病毒反应。
在香港，对 63 名因大流行性流感住院的成年人进行直接测序以检测 D222G 突变。通过实时 PCR 测量就诊时鼻咽病毒浓度，以评估上呼吸道的脱落情况。监测连续的上呼吸道和下呼吸道标本，以确定优先嗜性并记录对治疗的病毒学反应。
在患有严重肺炎的病例中，D222G 感染的频率为 17.4%，在需要重症监护的病例中为 26.7%。总共检测到在香港第一波和第二波传播的 4 例散发性 D222G 病例。D222G 感染与严重肺炎（100%比 32.2%，P=0.015）和重症监护入院（100%比 18.6%，P=0.002）显著相关。与野生型相比，D222G 在上呼吸道的病毒浓度较低，但在下呼吸道仍保持高浓度，尽管在上呼吸道经抗病毒治疗清除后仍存在。
这些观察结果表明，D222G 可能是从头产生的，从上呼吸道脱落的病毒较少，并且可能传染性较低，但对肺部的亲和性更高，对抗病毒治疗的抵抗力更强。D222G 与发生严重疾病的机会更高相关。需要下呼吸道标本才能可靠地检测到这种突变。
