Publication
Unmapped exome reads implicate a role for Anelloviridae in childhood HIV-1 long-term non-progression
Publisher:
Springer Science and Business Media LLC
Date:
19-03-2021
DOI:
10.1038/S41525-021-00185-W
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 ersity 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.