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

Article scientifique 2021 Anglais

Résumé

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.

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Mwesigwa, S., Williams, L., Retshabile, G., Katagirya, E., Mboowa, G., Mlotshwa, B., Kyobe, S., Kateete, D., Wampande, E., Wayengera, M., Mpoloka, S., Mirembe, A., Kasvosve, I., Morapedi, K., Kisitu, G., Kekitiinwa, A., Anabwani, G., Joloba, M., Matovu, E., Mulindwa, J., Noyes, H., Botha, G., (CAfGEN), C., Tsimako-Johnstone, M., Katabazi, F., Kigozi, E., Mathuba, K., Brown, C., Mardon, G., Matshaba, M., Hanchard, N. (2021). Unmapped exome reads implicate a role for Anelloviridae in childhood HIV-1 long-term non-progression. https://doi.org/10.1038/s41525-021-00185-w

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Auteur(s)

Savannah Mwesigwa Lesedi Williams Gaone Retshabile Eric Katagirya Gerald Mboowa Busisiwe Mlotshwa Samuel Kyobe David Patrick Kateete Eddie M. Wampande Misaki Wayengera Sununguko Wata Mpoloka Angella N. Mirembe Ishmael Kasvosve Koketso Morapedi Grace P. Kisitu Adeodata Kekitiinwa Gabriel Anabwani Moses Joloba Enock Matovu Julius Mulindwa Harry Noyes Gerrit Botha Collaborative African Genomics Network (CAfGEN) Masego Tsimako-Johnstone Fred Ashaba Katabazi Edgar Kigozi Keofentse Mathuba Chester Brown Graeme Mardon Mogomotsi Matshaba Neil A. Hanchard

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