Transmission patterns and evolution of respiratory syncytial virus in a community outbreak identified by genomic analysis.
Transmission patterns and evolution of respiratory syncytial virus in a community outbreak identified by genomic analysis.
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DOI：
10.1093/ve/vex006
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发表时间：
2017-01
期刊：
影响因子：
5.3
通讯作者：
Nokes DJ
中科院分区：
文献类型：
--
作者：
Agoti CN;Munywoki PK;Phan MVT;Otieno JR;Kamau E;Bett A;Kombe I;Githinji G;Medley GF;Cane PA;Kellam P;Cotten M;Nokes DJ
关于呼吸道合胞病毒（RSV）在季节性社区暴发期间的来源、传播和进化的详细信息仍然很少。对住院病例的附着 (G) 基因序列的分子分析表明，多种基因型和变种在流行期间共同传播，RSV 在连续季节中持续存在的特点是替换和多个新引入的变种。尚无研究明确 RSV 在当地社区和家庭层面的引入、传播和演变模式。我们对 2010 年肯尼亚沿海 12 平方公里区域内为期 6 个月的家庭 RSV 感染监测期间收集的 131 种 RSV A 组病毒进行了全基因组序列分析。 RSV 感染是通过每周两次对所有家庭成员进行定期的与症状无关的筛查来确定的。系统发育分析显示，9个家庭的RSV A病毒与GA2基因型密切相关，属于全球系统发育的一个分支。基因组分析允许检测七个家庭的家庭特异性变异。为了进行比较，仅使用 G 基因分析，仅在 9 个家庭中的一个中发现了家庭特异性变异。在宿主内部（在后续采样中从同一个人中识别出病毒）和宿主间（从不同家庭成员中识别出病毒）观察到核苷酸变化，这些变化与采样日期相结合，使得能够部分重建家庭内部传播链。家庭数据集的基因组进化率估计为 2.307 × 10 − 3（95%最高后验密度：0.935–4.165× 10 − 3）替换/位点/年。我们的结论是：(i) 在家庭层面，大多数 RSV 感染是由于引入单一病毒变种引起的，然后是家庭特定变异的积累；(ii) 完整病毒基因组的分析对于更好地了解病毒在社区中的传播至关重要。出现的一个关键问题是，通过为关键传播家庭成员接种疫苗来预防 RSV 在家庭内的引入或传播是否会导致社区范围内的进一步传播减少。
Detailed information on the source, spread and evolution of respiratory syncytial virus (RSV) during seasonal community outbreaks remains sparse. Molecular analyses of attachment (G) gene sequences from hospitalized cases suggest that multiple genotypes and variants co-circulate during epidemics and that RSV persistence over successive seasons is characterized by replacement and multiple new introductions of variants. No studies have defined the patterns of introduction, spread and evolution of RSV at the local community and household level. We present a whole genome sequence analysis of 131 RSV group A viruses collected during 6-month household-based RSV infection surveillance in Coastal Kenya, 2010 within an area of 12 km2. RSV infections were identified by regular symptom-independent screening of all household members twice weekly. Phylogenetic analysis revealed that the RSV A viruses in nine households were closely related to genotype GA2 and fell within a single branch of the global phylogeny. Genomic analysis allowed the detection of household-specific variation in seven households. For comparison, using only G gene analysis, household-specific variation was found only in one of the nine households. Nucleotide changes were observed both intra-host (viruses identified from same individual in follow-up sampling) and inter-host (viruses identified from different household members) and these coupled with sampling dates enabled a partial reconstruction of the within household transmission chains. The genomic evolutionary rate for the household dataset was estimated as 2.307 × 10 − 3 (95% highest posterior density: 0.935–4.165× 10 − 3) substitutions/site/year. We conclude that (i) at the household level, most RSV infections arise from the introduction of a single virus variant followed by accumulation of household specific variation and (ii) analysis of complete virus genomes is crucial to better understand viral transmission in the community. A key question arising is whether prevention of RSV introduction or spread within the household by vaccinating key transmitting household members would lead to a reduced onward community-wide transmission.