Dissecting HIV Virulence: Heritability of Setpoint Viral Load, CD4+ T-Cell Decline, and Per-Parasite Pathogenicity.
Dissecting HIV Virulence: Heritability of Setpoint Viral Load, CD4+ T-Cell Decline, and Per-Parasite Pathogenicity.
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DOI：
10.1093/molbev/msx246
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发表时间：
2018-01-01
影响因子：
10.7
通讯作者：
Swiss HIV Cohort Study
中科院分区：
文献类型：
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作者：
Bertels F;Marzel A;Leventhal G;Mitov V;Fellay J;Günthard HF;Böni J;Yerly S;Klimkait T;Aubert V;Battegay M;Rauch A;Cavassini M;Calmy A;Bernasconi E;Schmid P;Scherrer AU;Müller V;Bonhoeffer S;Kouyos R;Regoes RR;Swiss HIV Cohort Study
病原体菌株的毒力可能不同，因为它们在宿主中获得不同的负荷，或者因为它们诱导不同的致病机制，而与它们的负荷无关。在进化生态学中，后者被称为“每寄生虫致病性”。使用2014年参加瑞士HIV队列研究的HIV-1亚型B感染者的病毒载量和CD 4 + T细胞测量值，我们调查了毒力（以CD 4 + T细胞下降率衡量）和每种寄生虫的致病性是否可从供体遗传给受体。我们估计遗传力的供体-受体回归应用到196个以前确定的传输对，并通过系统发育混合模型应用到从HIV聚合酶序列推断的系统发育树。回归的CD 4 + T细胞下降和每寄生虫的致病性的传输对没有产生显着不同的遗传力估计为零。然而，使用系统发育混合模型，我们对CD 4 + T细胞下降的遗传率的最佳估计为17%（5-30%），对每寄生虫致病性的最佳估计为17%（4-29%）。此外，我们确认设定点病毒载量是可遗传的，并估计遗传率为29%（12-46%）。有趣的是，所有这些性状的进化模式与中性显著不同，并且与设定点病毒载量的稳定选择以及CD 4 + T细胞下降和每寄生虫致病性的定向选择最一致。我们的分析表明，病毒基因型影响毒力主要是通过调节每寄生虫的致病性，而通过设定点病毒载量的间接影响是次要的。
Pathogen strains may differ in virulence because they attain different loads in their hosts, or because they induce different disease-causing mechanisms independent of their load. In evolutionary ecology, the latter is referred to as “per-parasite pathogenicity”. Using viral load and CD4+ T-cell measures from 2014 HIV-1 subtype B-infected individuals enrolled in the Swiss HIV Cohort Study, we investigated if virulence—measured as the rate of decline of CD4+ T cells—and per-parasite pathogenicity are heritable from donor to recipient. We estimated heritability by donor–recipient regressions applied to 196 previously identified transmission pairs, and by phylogenetic mixed models applied to a phylogenetic tree inferred from HIV pol sequences. Regressing the CD4+ T-cell declines and per-parasite pathogenicities of the transmission pairs did not yield heritability estimates significantly different from zero. With the phylogenetic mixed model, however, our best estimate for the heritability of the CD4+ T-cell decline is 17% (5–30%), and that of the per-parasite pathogenicity is 17% (4–29%). Further, we confirm that the set-point viral load is heritable, and estimate a heritability of 29% (12–46%). Interestingly, the pattern of evolution of all these traits differs significantly from neutrality, and is most consistent with stabilizing selection for the set-point viral load, and with directional selection for the CD4+ T-cell decline and the per-parasite pathogenicity. Our analysis shows that the viral genotype affects virulence mainly by modulating the per-parasite pathogenicity, while the indirect effect via the set-point viral load is minor.
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影响因子：
6.4
作者：
Barbour, JD;Hecht, FM;Grant, RM
通讯作者：
Grant, RM
DOI：
10.1126/science.1254031
发表时间：
2014-07-11
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Carlson JM;Schaefer M;Monaco DC;Batorsky R;Claiborne DT;Prince J;Deymier MJ;Ende ZS;Klatt NR;DeZiel CE;Lin TH;Peng J;Seese AM;Shapiro R;Frater J;Ndung'u T;Tang J;Goepfert P;Gilmour J;Price MA;Kilembe W;Heckerman D;Goulder PJ;Allen TM;Allen S;Hunter E
通讯作者：
Hunter E
影响因子：
6.7
作者：
Hodcroft, Emma;Hadfield, Jarrod D.;Brown, Andrew J. Leigh
通讯作者：
Brown, Andrew J. Leigh
影响因子：
4.3
作者：
Bartha, Istvan;McLaren, Paul J.;Fellay, Jacques
通讯作者：
Fellay, Jacques
影响因子：
6.4
作者：
Baeten, Jared M.;Chohan, Bhavna;Overbaugh, Julie
通讯作者：
Overbaugh, Julie