Unmapped exome reads implicate a role for Anelloviridae in childhood HIV-1 long-term non-progression
Year: 2021
Type: article
Study design: Observational Study
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), withAnelloviridaeshowing 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 theAnelloviridaereads, 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.
Source: npj Genomic Medicine
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), Masego Tsimako-Johnstone, Fred. A. Katabazi, Edgar Kigozi, Keofentse Mathuba, Chester W. Brown, Graeme Mardon, Mogomotsi Matshaba, Neil A. Hanchard
Institutions: Makerere University, University of Botswana, Baylor College of Medicine Children’s Foundation, Botswana-Baylor Children's Clinical Center of Excellence, University of Liverpool, University of Cape Town, Institute of Infectious Disease and Molecular Medicine, University of Tennessee Health Science Center, Le Bonheur Children's Hospital, Baylor College of Medicine, National Institutes of Health, National Human Genome Research Institute
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,490
OpenAlex ID: W3136633095