Unmapped exome reads implicate a role for Anelloviridae in childhood HIV-1 long-term non-progression.
Unmapped exome reads implicate a role for Anelloviridae in childhood HIV-1 long-term non-progression.
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DOI：
10.1038/s41525-021-00185-w
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发表时间：
2021-03-19
影响因子：
5.3
通讯作者：
Hanchard NA
中科院分区：
文献类型：
--
作者：
Mwesigwa S;Williams L;Retshabile G;Katagirya E;Mboowa G;Mlotshwa B;Kyobe S;Kateete DP;Wampande EM;Wayengera M;Mpoloka SW;Mirembe AN;Kasvosve I;Morapedi K;Kisitu GP;Kekitiinwa AR;Anabwani G;Joloba ML;Matovu E;Mulindwa J;Noyes H;Botha G;Collaborative African Genomics Network (CAfGEN);TrypanoGEN Research Group;Brown CW;Mardon G;Matshaba M;Hanchard NA
人类免疫缺陷病毒（HIV）感染仍然是全球重大的公共卫生负担。病毒合并感染在 HIV 感染进展速度中的作用已被提出，但尚未经过实证检验，特别是在儿童中。我们从博茨瓦纳和乌干达 813 名 HIV 感染儿童的全外显子组测序 (WES) 数据中提取并分类了 42 种病毒，分为长期非进展者 (LTNP) 或快速进展者 (RP)。与博茨瓦纳相比，乌干达参与者的病毒群落多样性指数更高（p = 4.6 × 10−13），LTNP 中检测到的病毒序列比 RP 中更常见（24% vs 16%；p = 0.008；OR，1.9；95% CI，1.6–2.3），指环病毒科与LTNP 状态（p = 3 × 10−4；q = 0.004，OR，3.99；95% CI，1.74–10.25）。当按国家、性别和测序平台分层时，以及在调整年龄、性别、国家和测序平台的逻辑回归分析后，这种趋势仍然很明显（p = 0.02；q = 0.03；OR，7.3；95% CI，1.6-40.5）。占指环病毒科读数 95% 的 Torque teno 病毒 (TTV) 与免疫激活降低有关。我们确定了病毒合并感染与延长无艾滋病生存状态之间的关联，该关联可能可作为 LTNP 的生物标志物，并可以为儿童 HIV 进展提供机制见解，证明在队列研究中询问脱靶 WES 读数的附加价值。
Human immunodeficiency virus (HIV) infection remains a significant public health burden globally. The role of viral co-infection in the rate of progression of HIV infection has been suggested but not empirically tested, particularly among children. We extracted and classified 42 viral species from whole-exome sequencing (WES) data of 813 HIV-infected children in Botswana and Uganda categorised as either long-term non-progressors (LTNPs) or rapid progressors (RPs). The Ugandan participants had a higher viral community diversity index compared to Batswana (p = 4.6 × 10−13), and viral sequences were more frequently detected among LTNPs than RPs (24% vs 16%; p = 0.008; OR, 1.9; 95% CI, 1.6–2.3), with Anelloviridae showing strong association with LTNP status (p = 3 × 10−4; q = 0.004, OR, 3.99; 95% CI, 1.74–10.25). This trend was still evident when stratified by country, sex, and sequencing platform, and after a logistic regression analysis adjusting for age, sex, country, and the sequencing platform (p = 0.02; q = 0.03; OR, 7.3; 95% CI, 1.6–40.5). Torque teno virus (TTV), which made up 95% of the Anelloviridae reads, has been associated with reduced immune activation. We identify an association between viral co-infection and prolonged AIDs-free survival status that may have utility as a biomarker of LTNP and could provide mechanistic insights to HIV progression in children, demonstrating the added value of interrogating off-target WES reads in cohort studies.
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影响因子：
64.8
作者：
Gurdasani, Deepti;Carstensen, Tommy;Tekola-Ayele, Fasil;Pagani, Luca;Tachmazidou, Ioanna;Hatzikotoulas, Konstantinos;Karthikeyan, Savita;Iles, Louise;Pollard, Martin O.;Choudhury, Ananyo;Ritchie, GrahamR. S.;Xue, Yali;Asimit, Jennifer;Nsubuga, Rebecca N.;Young, Elizabeth H.;Pomilla, Cristina;Kivinen, Katja;Rockett, Kirk;Kamali, Anatoli;Doumatey, Ayo P.;Asiki, Gershim;Seeley, Janet;Sisay-Joof, Fatoumatta;Jallow, Muminatou;Tollman, Stephen;Mekonnen, Ephrem;Ekong, Rosemary;Oljira, Tamiru;Bradman, Neil;Bojang, Kalifa;Ramsay, Michele;Adeyemo, Adebowale;Bekele, Endashaw;Motala, Ayesha;Norris, Shane A.;Pirie, Fraser;Kaleebu, Pontiano;Kwiatkowski, Dominic;Tyler-Smith, Chris;Rotimi, Charles;Zeggini, Eleftheria;Sandhu, Manjinder S.
通讯作者：
Sandhu, Manjinder S.
影响因子：
30.3
作者：
Demeulemeester, Jonas;Vets, Sofie;Gijsbers, Rik
通讯作者：
Gijsbers, Rik
影响因子：
8
作者：
Berhane, R;Bagenda, D;Olness, K
通讯作者：
Olness, K
影响因子：
64.5
作者：
De Vlaminck I;Khush KK;Strehl C;Kohli B;Luikart H;Neff NF;Okamoto J;Snyder TM;Cornfield DN;Nicolls MR;Weill D;Bernstein D;Valantine HA;Quake SR
通讯作者：
Quake SR
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y