Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Center, Peking Union Medical Collage (PUMC), Beijing 100021, China.
Virol J. 2010 Nov 18;7:325. doi: 10.1186/1743-422X-7-325.
The novel pandemic A (H1N1) virus was first identified in Mexico in April 2009 and since then it spread world wide over a short period of time. Although the virus infection is generally associated with mild disease and a relatively low mortality, it is projected that mutations in specific regions of the viral genome, especially within the receptor binding domain of the hemagglutinin (HA) protein could result in more virulent virus stains, leading to a more severe pandemic.
Here, we found that a single amino acid substitution of Asp-to-Gly at position 222 in the HA protein of the A (H1N1) virus occurred after two passage propagation in the allantoic cavities of chicken embryonated eggs, and this single residue variation dramatically increased the viral replication ability in MDCK cells and pathogenicity in BALB/c mice.
A substitution of Asp-to-Gly at position 222 in the HA protein was prone to occur under positive selection pressures, and this single amino acid mutation could dramatically increase the virus replication ability in vitro and pathogenicity in vivo. Our finding offers a better understanding of the transmission and evolution of the 2009 pandemic A (H1N1) virus and brings attention to further potentially severe influenza pandemic that may result from cross-host evolution of the influenza viruses.
新型 A（H1N1）病毒于 2009 年 4 月在墨西哥首次被发现，此后在短时间内迅速传播到世界各地。尽管该病毒感染通常与轻度疾病和相对较低的死亡率相关，但据预测，病毒基因组特定区域（特别是血凝素（HA）蛋白的受体结合域）的突变可能导致更具毒性的病毒株，从而引发更严重的大流行。
在这里，我们发现 A（H1N1）病毒的 HA 蛋白在鸡胚尿囊腔中连续传代两次后，第 222 位的天冬氨酸被甘氨酸取代，这种单一残基的变化极大地提高了病毒在 MDCK 细胞中的复制能力和在 BALB/c 小鼠中的致病性。
HA 蛋白第 222 位的天冬氨酸到甘氨酸取代容易受到正选择压力的影响，这种单一的氨基酸突变可以显著提高病毒在体外的复制能力和体内的致病性。我们的发现更好地理解了 2009 年大流行 A（H1N1）病毒的传播和进化，并引起了对可能由流感病毒跨宿主进化引起的进一步严重流感大流行的关注。
