Tropical Infectious Diseases Research and Education Centre, Universiti Malaya, Kuala Lumpur 50603, Malaysia.
Institute for Advanced Studies, Universiti Malaya, Kuala Lumpur 50603, Malaysia.
Viruses. 2022 Apr 30;14(5):942. doi: 10.3390/v14050942.
Getah virus is an emerging mosquito-borne animal pathogen. Four phylogenetic groups of GETV, Group I (GI), GII, GIII and GIV, were identified. However, only the GETV GIII was associated with disease epidemics suggesting possible virulence difference in this virus group. Here, we compared the genetic and in vitro phenotypic characteristics between the epidemic and non-epidemic GETV. Our complete coding genome sequence analyses revealed several amino acid substitutions unique to the GETV GIII and GIV groups, which were found mainly in the hypervariable domain of nsP3 and E2 proteins. Replication kinetics of the epidemic (GIII MI-110 and GIII 14-I-605) and non-epidemic GETV strains (prototype GI MM2021 and GIV B254) were compared in mammalian Vero cells and mosquito C6/36 and U4.4 cells. In all cells used, both epidemic GETV GIII MI-110 and GIII 14-I-605 strains showed replication rates and mean maximum titers at least 2.7-fold and 2.3-fold higher than those of GIV B254, respectively (Bonferroni posttest, p < 0.01). In Vero cells, the epidemic GETV strains caused more pronounced cytopathic effects in comparison to the GIV B254. Our findings suggest that higher virus replication competency that produces higher virus titers during infection may be the main determinant of virulence and epidemic potential of GETV.
基孔肯雅病毒是一种新兴的蚊媒动物病原体。已鉴定出四种基孔肯雅病毒(GETV)的进化枝群,即 I 群(GI)、GII、GIII 和 GIV。然而,只有 GETV GIII 与疾病流行有关,这表明该病毒群可能存在毒力差异。在这里,我们比较了流行和非流行 GETV 的遗传和体外表型特征。我们对完整编码基因组序列的分析揭示了 GETV GIII 和 GIV 群特有的几个氨基酸取代,这些取代主要存在于 nsP3 和 E2 蛋白的高变区。在哺乳动物 Vero 细胞和蚊子 C6/36 和 U4.4 细胞中比较了流行(GIII MI-110 和 GIII 14-I-605)和非流行 GETV 株(原型 GI MM2021 和 GIV B254)的复制动力学。在所有使用的细胞中,流行的 GETV GIII MI-110 和 GIII 14-I-605 株的复制率和平均最大滴度至少比 GIV B254 高 2.7 倍和 2.3 倍(Bonferroni 后检验,p < 0.01)。在 Vero 细胞中,与 GIV B254 相比,流行的 GETV 株引起更明显的细胞病变效应。我们的研究结果表明,在感染过程中产生更高病毒滴度的更高病毒复制能力可能是 GETV 毒力和流行潜力的主要决定因素。