A comparative study of human TLR 7/8 stimulatory trimer compositions in influenza A viral genomes.
A comparative study of human TLR 7/8 stimulatory trimer compositions in influenza A viral genomes.
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DOI：
10.1371/journal.pone.0030751
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Chen SM
中科院分区：
文献类型：
--
作者：
Yang CW;Chen SM
单链RNA病毒基因组的变异对其感染性和致病性有两方面的影响。首先，病毒基因组序列的变异会导致病毒蛋白序列和活性的变化。其次，病毒基因组序列变异在核苷酸组成水平上产生多样性，在病毒RNA与宿主Toll样受体(TLRs)相互作用中产生多样性。基于这种多样性的病毒基因组分型方法尚未建立。在这项研究中，我们提出了一种新的基因组性状，称为TLR刺激三聚体组成(TSTC)和两个定量指标，得分S和得分N，称为TLR刺激得分(TSS)。利用10,994株甲型流感病毒和251株乙型流感病毒的全基因组序列进行序列分析，发现不同宿主分离的甲型流感病毒和乙型流感病毒的S评分和N评分存在一定的差异性。此外，我们还发现，S评分越低，IAV的致病性越高，流行的可能性越大。最后，我们使用S评分和N评分构建Logistic回归模型来识别高致病性或高流行潜力的IAV毒株。TSTC分析结果表明，人和禽源IAV基因组(除片段3外)存在较大的差异，Score S表明，片段1、2、3和4可能是刺激人TLR7和8的主要决定因素。我们还发现，评分较低的S值与IAV的高致病性和大流行潜力有关。TSS衍生的Logistic回归模型的π值有助于识别具有高致病性和大流行潜力的新出现的IAV。
Variation in the genomes of single-stranded RNA viruses affects their infectivity and pathogenicity in two ways. First, viral genome sequence variations lead to changes in viral protein sequences and activities. Second, viral genome sequence variation produces diversity at the level of nucleotide composition and diversity in the interactions between viral RNAs and host toll-like receptors (TLRs). A viral genome-typing method based on this type of diversity has not yet been established. In this study, we propose a novel genomic trait called the “TLR stimulatory trimer composition” (TSTC) and two quantitative indicators, Score S and Score N, named “TLR stimulatory scores” (TSS). Using the complete genome sequences of 10,994 influenza A viruses (IAV) and 251 influenza B viruses, we show that TSTC analysis reveals the diversity of Score S and Score N among the IAVs isolated from various hosts. In addition, we show that low values of Score S are correlated with high pathogenicity and pandemic potential in IAVs. Finally, we use Score S and Score N to construct a logistic regression model to recognize IAV strains that are highly pathogenic or have high pandemic potential. Results from the TSTC analysis indicate that there are large differences between human and avian IAV genomes (except for segment 3), as illustrated by Score S. Moreover, segments 1, 2, 3 and 4 may be major determinants of the stimulatory activity exerted on human TLRs 7 and 8. We also find that a low Score S value is associated with high pathogenicity and pandemic potential in IAV. The π value from the TSS-derived logistic regression model is useful for recognizing emerging IAVs that have high pathogenicity and pandemic potential.
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影响因子：
64.8
作者：
Rambaut, Andrew;Pybus, Oliver G.;Holmes, Edward C.
通讯作者：
Holmes, Edward C.
DOI：
10.1073/pnas.85.2.324
发表时间：
1988-01-01
影响因子：
11.1
作者：
KAWAOKA, Y;WEBSTER, RG
通讯作者：
WEBSTER, RG
影响因子：
3.7
作者：
Greninger AL;Chen EC;Sittler T;Scheinerman A;Roubinian N;Yu G;Kim E;Pillai DR;Guyard C;Mazzulli T;Isa P;Arias CF;Hackett J;Schochetman G;Miller S;Tang P;Chiu CY
通讯作者：
Chiu CY
影响因子：
11.8
作者：
Chen GW;Shih SR
通讯作者：
Shih SR
影响因子：
4.4
作者：
Wang, Jennifer P.;Liu, Ping;Libraty, Daniel H.
通讯作者：
Libraty, Daniel H.