Emergence of genotype Cosmopolitan of dengue virus type 2 and genotype III of dengue virus type 3 in Thailand

Dengue is a mosquito-borne disease that has spread to over 100 countries. Dengue fever is caused by dengue virus (DENV), which belongs to the Flavivirus genus of the family Flaviviridae. DENV comprises 4 serotypes (DENV-1 to DENV-4), and each serotype is divided into distinct genotypes. Thailand is an endemic area where all 4 serotypes of DENV co-circulate. To understand the current genotype distribution of DENVs in Thailand, we enrolled 100 cases of fever with dengue-like symptoms at the Bamrasnaradura Infectious Diseases Institute during 2016–2017. Among them, 37 cases were shown to be dengue-positive by real-time PCR. We were able to isolate DENVs from 21 cases, including 1 DENV-1, 8 DENV-2, 4 DENV-3, and 8 DENV-4. To investigate the divergence of the viruses, RNA was extracted from isolated DENVs and viral near-whole genome sequences were determined. Phylogenetic analysis of the obtained viral sequences revealed that DENV-2 genotype Cosmopolitan was co-circulating with DENV-2 genotype Asian-I, the previously predominating genotype in Thailand. Furthermore, DENV-3 genotype III was found instead of DENV-3 genotype II. The DENV-2 Cosmopolitan and DENV-3 genotype III found in Thailand were closely related to the respective strains found in nearby countries. These results indicated that DENVs in Thailand have increased in genotypic diversity, and suggested that the DENV genotypic shift observed in other Asian countries also might be taking place in Thailand.

登革热是一种经蚊媒传播的传染病，目前已在全球100余个国家流行。登革热由登革病毒（Dengue Virus, DENV）引发，该病毒隶属于黄病毒科（Flaviviridae）黄病毒属（Flavivirus）。登革病毒共分为4个血清型（DENV-1至DENV-4），每一血清型又可进一步划分为不同的基因型。泰国是登革热地方性流行区，境内4种登革病毒血清型均存在共同循环传播现象。为明确泰国当前登革病毒的基因型分布特征，研究团队于2016—2017年期间，在班拉沙拉杜拉传染病研究所（Bamrasnaradura Infectious Diseases Institute）招募了100例表现出登革热样症状的发热患者。经实时荧光定量PCR（real-time PCR）检测，其中37例样本呈登革病毒阳性。研究人员成功从21例阳性样本中分离得到登革病毒，具体毒株类型包括1株DENV-1、8株DENV-2、4株DENV-3以及8株DENV-4。为探究这些分离毒株的进化分化情况，研究人员从登革病毒分离物中提取RNA，并完成了病毒近全基因组序列的测定。对获得的病毒序列开展系统发育分析后发现，DENV-2的Cosmopolitan基因型与此前在泰国占主导地位的DENV-2亚洲I（Asian-I）基因型出现了共同循环传播的现象。此外，研究还发现泰国境内的DENV-3基因型II已被DENV-3基因型III取代。本次在泰国检出的DENV-2 Cosmopolitan基因型与DENV-3基因型III毒株，与周边国家检出的对应毒株亲缘关系极为密切。上述研究结果表明，泰国境内登革病毒的基因型多样性显著提升，同时提示其他亚洲国家曾报道的登革病毒基因型转变现象，或许也正在泰国发生。