Reversion to ancestral Zika virus NS1 residues increases competence of Aedes albopictus.
Reversion to ancestral Zika virus NS1 residues increases competence of Aedes albopictus.
复制标题
向祖先寨卡病毒NS1残基的恢复增加了伊德斯白细胞的能力。
DOI：
10.1371/journal.ppat.1008951
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发表时间：
2020-10
期刊：
影响因子：
6.7
通讯作者：
Ciota AT
中科院分区：
文献类型：
--
作者：
Kuo L;Jaeger AS;Banker EM;Bialosuknia SM;Mathias N;Payne AF;Kramer LD;Aliota MT;Ciota AT
蚊子物种特异性差异和病毒株特异性差异都影响病媒能力。本实验室以前的研究结果表明，N.美国蚊子支持埃及伊蚊比Ae更有能力的研究。白纹伊蚊对美国寨卡病毒（ZIKV）毒株的敏感性，并证明美国Ae.白纹伊蚊对祖先亚洲ZIKV毒株具有更高的感受态。A982 V是在美国爆发之前获得的NS 1基因中的氨基酸替换，已被证明可以增加Ae的能力。埃及人。因此，我们假设NS 1的变异性可能导致物种特异性差异，并基于2016年洪都拉斯ZIKV分离株（ZIKV-WTic）开发了一种反向遗传学系统，以评估单个氨基酸取代的表型相关性。除A982 V外，我们还评价了在美洲流通期间获得的G894 A。982和894的祖先残基的逆转增加了感染性，传播性和病毒载量在Ae。白纹伊蚊，但没有影响的能力或复制在Ae。埃及人。此外，尽管测量了NS 1分泌的宿主细胞特异性差异，但哺乳动物细胞中的分泌相对于蚊子细胞显著更高，尽管先前有报道，但未检测到分泌的菌株特异性差异。这些结果表明，在NS 1的个别突变可以影响能力在一个物种特异性的方式独立的差异，在NS 1分泌，并进一步表明，祖先NS 1残基赋予Ae的能力增加。白纹伊蚊最后，Ifnar 1-/-小鼠的实验感染表明，这些NS 1取代可以影响宿主中的病毒复制，具体地说，G894 A可以代表具有某些病毒遗传背景的A982 V适应性丧失后的补偿性变化。总之，这些数据表明上位相互作用在无脊椎动物和脊椎动物宿主中ZIKV适应性中的可能作用，并证明在美国Ae.白纹伊蚊可能会出现促进ZIKV在美洲出现和快速传播的因素，以及ZIKV传播中菌株变异和适应性进化的具体作用尚未完全了解。已经表明，在美国爆发之前获得的NS 1基因中的氨基酸替换赋予Ae的感染性增加。埃及人。因此，我们假设NS 1的变异性可能有助于物种特异性差异。为了研究ZIKV NS 1在Ae.埃及伊蚊和埃及伊蚊。我们利用反向遗传学回复到祖先NS 1残基，并表征所得突变株。逆转增加了Ae的感染性，传播性和病毒载量。白纹伊蚊，但没有影响的能力或复制在Ae。埃及人。此外，我们使用ZIKV小鼠模型评估了这些突变对NS 1分泌以及毒力和病毒血症动力学的影响。NS 1分泌，以及脊椎动物的发病率或死亡率，菌株之间是相似的，但病毒血症水平的菌株特异性差异进行了鉴定。这些结果表明，在NS 1的个别突变可以影响能力在一个物种特异性的方式独立的差异，在NS 1分泌，并进一步表明，祖先NS 1残基赋予Ae的能力增加。白纹伊蚊此外，将这些数据与先前的研究进行对比表明上位相互作用在无脊椎动物和脊椎动物宿主中的ZIKV适应性中的作用。
Both mosquito species-specific differences and virus strain -specific differences impact vector competence. Previous results in our laboratory with individual populations of N. American mosquitoes support studies suggesting Aedes aegypti are more competent than Ae. albopictus for American Zika virus (ZIKV) strains and demonstrate that U.S. Ae. albopictus have higher competence for an ancestral Asian ZIKV strain. A982V, an amino acid substitution in the NS1 gene acquired prior to the American outbreak, has been shown to increase competence in Ae. aegypti. We hypothesized that variability in the NS1 could therefore contribute to species-specific differences and developed a reverse genetics system based on a 2016 ZIKV isolate from Honduras (ZIKV-WTic) to evaluate the phenotypic correlates of individual amino acid substitutions. In addition to A982V, we evaluated G894A, which was acquired during circulation in the Americas. Reversion of 982 and 894 to ancestral residues increased infectivity, transmissibility and viral loads in Ae. albopictus but had no effect on competence or replication in Ae. aegypti. In addition, while host cell-specific differences in NS1 secretion were measured, with significantly higher secretion in mammalian cells relative to mosquito cells, strain-specific differences in secretion were not detected, despite previous reports. These results demonstrate that individual mutations in NS1 can influence competence in a species-specific manner independent of differences in NS1 secretion and further indicate that ancestral NS1 residues confer increased competence in Ae. albopictus. Lastly, experimental infections of Ifnar1-/- mice demonstrated that these NS1 substitutions can influence viral replication in the host and, specifically, that G894A could represent a compensatory change following a fitness loss from A982V with some viral genetic backgrounds. Together these data suggest a possible role for epistatic interactions in ZIKV fitness in invertebrate and vertebrate hosts and demonstrate that strains with increased transmission potential in U.S. Ae. albopictus could emerge. The factors that facilitated the emergence and rapid dissemination of ZIKV in the Americas, and the specific role of strain variation and adaptive evolution in ZIKV transmission, are not fully understood. It has been shown that an amino acid substitution in the NS1 gene acquired prior to the American outbreak confers increased infectivity in Ae. aegypti. Therefore, we hypothesized that variability in the NS1 could contribute to species-specific differences. To investigate the role of the ZIKV NS1 in competence of both Ae. aegypti and Ae. albopictus we utilized reverse genetics to revert to the ancestral NS1 residues and characterized the resultant mutant strains. Reversions increased infectivity, transmissibility and viral loads in Ae. albopictus but had no effect on competence or replication in Ae. aegypti. Additionally, we assessed the effect of these mutations on NS1 secretion and both virulence and viremia kinetics using a ZIKV mouse model. NS1 secretion, as well as vertebrate morbidity or mortality, were similar among strains, yet strain-specific differences in viremia levels were identified. These results demonstrate that individual mutations in NS1 can influence competence in a species-specific manner independent of differences in NS1 secretion and further indicate that ancestral NS1 residues confer increased competence in Ae. albopictus. Moreover, contrasting these data with previous studies suggests a role for epistatic interactions in ZIKV fitness in invertebrate and vertebrate hosts.
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影响因子：
3.7
作者：
Diagne CT;Diallo D;Faye O;Ba Y;Faye O;Gaye A;Dia I;Faye O;Weaver SC;Sall AA;Diallo M
通讯作者：
Diallo M
影响因子：
3.8
作者：
Lednicky J;Beau De Rochars VM;El Badry M;Loeb J;Telisma T;Chavannes S;Anilis G;Cella E;Ciccozzi M;Rashid M;Okech B;Salemi M;Morris JG Jr
通讯作者：
Morris JG Jr
影响因子：
3.8
作者：
Chouin-Carneiro T;Vega-Rua A;Vazeille M;Yebakima A;Girod R;Goindin D;Dupont-Rouzeyrol M;Lourenço-de-Oliveira R;Failloux AB
通讯作者：
Failloux AB
受感染宿主血清中的黄病毒 NS1 蛋白增强蚊子获取病毒的能力
影响因子：
28.3
作者：
Liu, Jianying;Liu, Yang;Nie, Kaixiao;Du, Senyan;Qiu, Jingjun;Pang, Xiaojing;Wang, Penghua;Cheng, Gong
通讯作者：
Cheng, Gong