Ariyaratne Dinuka, Jayadas Tibutius Thanesh Pramanayagam, Jeewandara Chandima, Senadheera Bhagya, De Silva Malithi, Gomes Laksiri, Bary Farha, Syenina Ayesa, Ranasinghe Diyanath, Kuruppu Heshan, Wijewickrama Ananda, Ooi Eng Eong, Malavige Gathsaurie Neelika
University of Sri Jayewardenepura.
Duke-NUS Medical School.
Res Sq. 2025 Jun 29:rs.3.rs-6726277. doi: 10.21203/rs.3.rs-6726277/v1.
Surveillance and characterization of different dengue virus (DENV) lineages of different serotypes causing outbreaks is crucial for initiation of timely dengue control measures and for implementing dengue vaccines. Therefore, we characterized the DENV-2 strains in Sri Lanka from 2016, until end of 2023 and their evolutionary dynamics to understand the geographical spread and mutations arising with the DENV-2 serotypes in Sri Lanka.
Sequencing was carried out on 80 DENV-2 samples collected from patients with acute dengue recruited from 2016 to 2018 and on 12 DENV-2 samples from 2022 to 2023 using Oxford Nanopore Technology. Phylogenetic analysis was carried out using the IQ-TREE tool within Galaxy to construct a phylogenetic tree from the aligned sequence data. The sequences were also analyzed for non-synonymous amino acid changes in the envelope and NS1 regions.
The Sri Lankan DENV-2 sequences circulating from 2016 to end of 2023 were found to belong to genotype II.F.1 lineage. They were closely related to strains circulating during the same period in South Asia and Southeast Asia. We identified 15 non-synonymous mutations within the envelope region and 22 non-synonymous mutations within the NS1 region, with 7 non-synonymous mutations within the E region (M6I, Q52H, E71A, V129I, N390S, I484V, T478S) and 10 non-synonymous mutations within the NS1 region (S80T, T117A, Q131H, K174R, F178S, N222S, L247F, I264T, T265A, K272R) seen in all sequenced samples. Some of these mutations were previously shown to be associated with increase in viral replication, NS1 secretion and immune evasion, while some have not been reported elsewhere.
Given the increase in dengue transmission in many countries, it is important to further strengthen DENV surveillance for studying the evolutionary patterns of the DENV to initiate timely and appropriate control measures.
监测和鉴定导致疫情爆发的不同血清型登革病毒（DENV）谱系，对于及时启动登革热控制措施和实施登革热疫苗至关重要。因此，我们对2016年至2023年底斯里兰卡的DENV-2毒株及其进化动态进行了鉴定，以了解DENV-2血清型在斯里兰卡的地理传播和出现的突变。
使用牛津纳米孔技术对2016年至2018年招募的急性登革热患者的80份DENV-2样本以及2022年至2023年的12份DENV-2样本进行测序。使用Galaxy中的IQ-TREE工具进行系统发育分析，从比对后的序列数据构建系统发育树。还对包膜和NS1区域的非同义氨基酸变化进行了序列分析。
发现2016年至2023年底在斯里兰卡传播的DENV-2序列属于基因型II.F.1谱系。它们与同期在南亚和东南亚传播的毒株密切相关。我们在包膜区域鉴定出15个非同义突变，在NS1区域鉴定出22个非同义突变，在所有测序样本中，E区域有7个非同义突变（M6I、Q52H、E7A、V129I、N390S、I484V、T478S），NS1区域有10个非同义突变（S80T、T117A、Q131H、K174R、F178S、N222S、L247F、I264T、T265A、K272R）。其中一些突变先前已被证明与病毒复制增加、NS1分泌和免疫逃逸有关，而有些突变在其他地方尚未见报道。
鉴于许多国家登革热传播增加，进一步加强DENV监测以研究DENV的进化模式，从而及时启动适当的控制措施非常重要。
