Unmapped exome reads implicate a role for <i>Anelloviridae</i> in childhood HIV-1 long-term non-progression



Mwesigwa, Savannah, Williams, Lesedi, Retshabile, Gaone, Katagirya, Eric, Mboowa, Gerald, Mlotshwa, Busisiwe, Kyobe, Samuel, Kateete, David P, Wampande, Eddie Mujjwiga, Wayengera, Misaki
et al (show 16 more authors) (2021) Unmapped exome reads implicate a role for <i>Anelloviridae</i> in childhood HIV-1 long-term non-progression. NPJ GENOMIC MEDICINE, 6 (1). 24-.

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Abstract

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<sup>-13</sup>), 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<sup>-4</sup>; 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.

Item Type: Article
Uncontrolled Keywords: Collaborative African Genomics Network (CAfGEN), TrypanoGEN Research Group
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User: Symplectic Admin
Date Deposited: 25 Mar 2021 08:21
Last Modified: 18 Oct 2023 17:06
DOI: 10.1038/s41525-021-00185-w
Open Access URL: http://doi.org/10.1038/s41525-021-00185-w
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3118131