Molecular study of influenza C virus evolution

我们对1964年至1988年在日本分离的20株丙型流感病毒株的血凝素酯酶（HE）基因进行了测序，并与其他国家分离的10株病毒株的序列进行了联合进化分析。以下是所得结果的总结.分析的日本分离株可分为四个不同的谱系（I-IV）。然而，目前，三个谱系（I，II，IV）在我国可能是共同传播的，因为1977年以后根本没有分离出属于谱系III（以青森/74为代表）的病毒。在日本境外分离的10株病毒均属于目前在我国流行的三个谱系之一，这表明丙型流感病毒能够在全球范围内传播。通过比较1971 - 1988年Ⅰ系分离株的HE基因序列，估计HE基因的进化速率为0.509 × 10 ^置换/位点/年，表明HE基因的进化比甲型流感病毒HA基因慢得多.<-3>我们以前报道过，在HE蛋白中，大多数中和表位聚集在残基180至214之间的区域。在本研究中变得清楚的是，该结构域在属于不同谱系的毒株之间变化很大，但在属于相同谱系的毒株之间几乎相同，这提高了抗体压力可能在产生新谱系中发挥作用的可能性，但一旦建立了这样的谱系，即使在抗体压力存在的情况下，病毒也不再能够经历抗原性变化，大概是因为功能限制。

We sequenced the hemagglutinin-esterase (HE) genes of 20 influenza C strains isolated in Japan between 1964 and 1988 and performed a combined evolutionary analysis with the sequences of 10 strains isolated in other countries. The followings are the summaries of the results obtained.1. The Japanese isolates analyzed could be divided into four distinct lineages (I-IV). At present, however, three lineages (I,II,IV) seemes to be cocirculating in our country because no virus belonging to lineage III (represented by Aomori/74) has been isolated at all after 1977.2. The 10 strains isolated outside Japan were all found to belong to one of the three lineages currently circulating in our country, suggesting that influenza C virus is capable of spreading worldwide.3. By comparing the HE gene sequence among the 1971-1988 isolates that belong to lineage I, the evolutionary rate of HE gene was estimated to be 0.509x10^<-3> substitutions/site/year, indicating that the HE gene evolves much more slowly than the HA gene of influenza A virus.4. We reported previously that in the HE protein most of neutralizing epitopes are clustered in the region spanning from residue 180 to 214. It became clear in the present study that this domain is considerably variable among the strains belonging to different lineages but is nearly identical among the strains belonging to the same lineage, raising the possibility that antibody pressure may have playd a role in producing new lineage but that once such a lineage was established, the virus was no longer able to undergo antigenic changes even in the presence of antibody pressure, presumably because of the hunctional constraints.