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

• Main Authors: Savannah Mwesigwa, Lesedi Williams, Gaone Retshabile, Eric Katagirya, Gerald Mboowa, Busisiwe Mlotshwa, Samuel Kyobe, David P. Kateete, Eddie Mujjwiga Wampande, Misaki Wayengera, Sununguko Wata Mpoloka, Angella N. Mirembe, Ishmael Kasvosve, Koketso Morapedi, Grace P. Kisitu, Adeodata R. Kekitiinwa, Gabriel Anabwani, Moses L. Joloba, Enock Matovu, Julius Mulindwa, Harry Noyes, Gerrit Botha, Collaborative African Genomics Network (CAfGEN), TrypanoGEN Research Group, Chester W. Brown, Graeme Mardon, Mogomotsi Matshaba, Neil A. Hanchard
• Format: Article
• Language: English
• Published: Nature Publishing Group 2021-03-01
• Series: npj Genomic Medicine
• Online Access: https://doi.org/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 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.