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

Mwesigwa, S. et al. (2021) Unmapped exome reads implicate a role for Anelloviridae in childhood HIV-1 long-term non-progression. npj Genomic Medicine, 6(1), 24. (doi: 10.1038/s41525-021-00185-w) (PMID:33741997) (PMCID:PMC7979878)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: MacLeod, Professor Annette
• Authors: Mwesigwa, S., Williams, L., Retshabile, G., Katagirya, E., Mboowa, G., Mlotshwa, B., Kyobe, S., Kateete, D. P., Wampande, E. M., Wayengera, M., Mpoloka, S. W., Mirembe, A. N., Kasvosve, I., Morapedi, K., Kisitu, G. P., Kekitiinwa, A. R., Anabwani, G., Joloba, M. L., Matovu, E., Mulindwa, J., Noyes, H., Botha, G., TrypanoGEN Research Group, , Brown, C. W., Mardon, G., Matshaba, M., and Hanchard, N. A.
• College/School: College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
• Journal Name: npj Genomic Medicine
• Publisher: Nature Research
• ISSN: 2056-7944
• ISSN (Online): 2056-7944
• Published Online: 19 March 2021
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in npj Genomic Medicine 6(1):24
• Publisher Policy: Reproduced under a Creative Commons licence