Wittke V, Robb T E, Thu H M, Nisalak A, Nimmannitya S, Kalayanrooj S, Vaughn D W, Endy T P, Holmes E C, Aaskov J G
School of Life Sciences, Queensland University of Technology, Brisbane, Australia.
Virology. 2002 Sep 15;301(1):148-56. doi: 10.1006/viro.2002.1549.
Strains of dengue 3 (DEN-3) virus circulating in Thailand prior to 1992 appear to have disappeared from that location and to have been replaced by two new lineages which have evolved locally, rather than being introduced. Similar DEN-3 virus extinctions may have occurred previously in Thailand in 1962 and 1973. Although no causal relationship could be shown, this strain replacement event was accompanied by DEN-3 replacing DEN-2 as the serotype recovered most frequently from patients in Thailand. Although this implies a change in selection pressure, we found no evidence for positive natural selection at the level of either the E protein or the E protein gene. Further, the extinction of the pre-1992 strains and the appearance of the new lineages occurred during an interepidemic period, suggesting that a genetic bottleneck, rather than selection, might have been important in the emergence of these two new strains of virus. The pre-1992 DEN-3 virus lineage could still be found in 1998, to the west, in Myanmar. The ratio of nonsynonymous-to-synonymous nucleotide changes within a DEN-3 virus population from a single patient was less than the ratio among the consensus sequences of DEN-3 viruses from different patients, suggesting that many of the nonsynonymous nucleotide changes which occurred naturally in the E protein were deleterious and removed by purifying selection.
1992年之前在泰国传播的登革热3型（DEN-3）病毒株似乎已从该地区消失，并被在当地进化而非引入的两个新谱系所取代。类似的DEN-3病毒灭绝事件可能此前于1962年和1973年在泰国发生过。尽管无法证明存在因果关系，但这种毒株替代事件伴随着DEN-3取代DEN-2成为泰国患者中最常检出的血清型。虽然这意味着选择压力发生了变化，但我们未发现E蛋白或E蛋白基因水平上存在正自然选择的证据。此外，1992年前毒株的灭绝和新谱系的出现发生在疫情间期，这表明遗传瓶颈而非选择可能在这两种新病毒株的出现中起了重要作用。1992年前的DEN-3病毒谱系在1998年仍能在西部的缅甸发现。来自单个患者的DEN-3病毒群体内非同义核苷酸变化与同义核苷酸变化的比率低于来自不同患者的DEN-3病毒一致序列之间的比率，这表明E蛋白中自然发生的许多非同义核苷酸变化是有害的，并通过纯化选择被去除。
