Abstract

Apolipoprotein L1 (APOL1), an innate immune factor against African trypanosoma brucei, inhibits HIV-1 in vitro. The impact of APOL1 G1-G2 variants on HIV-1-associated opportunistic infections (OIs) is unknown. Here, we report findings from a metaanalysis of four HIV/AIDS prospective cohorts (ALIVE, LSOCA, MACS, and WIHS) including 2066 African American participants. Using a global test combining all four cohorts, carriage of two APOL1 variant alleles is associated with a 50% reduction in odds of OI (combined OR 0.50, 95% CI 0.33-0.76). Subgroup analysis of OI etiological categories (viral, parasitic, fungal and Mycobacterial) suggests the possibility of specific protection from fungal infections (OR 0.54. 95% CI 0.32-0.93; PBonferroni corrected = 0.08). We observe an association of APOL1 variant alleles with host protection against OI in HIV-positive individuals. The study suggests a broader role of APOL1 variant alleles in innate immunity in vivo.

An et al. determine the presence of variants of the innate immune factor APOL1 in four cohorts of HIV-positive patients. The study suggests that APOL1 might confer carriers of two variant alleles protection from HIV related opportunistic infections, especially fungal infections.

Details

Title
APOL1 variant alleles associate with reduced risk for opportunistic infections in HIV infection
Author
An, Ping 1   VIAFID ORCID Logo  ; Efe, Sezgin 2   VIAFID ORCID Logo  ; Kirk, Gregory D 3 ; Duggal Priya 4   VIAFID ORCID Logo  ; Binns-Roemer, Elizabeth 1 ; Nelson, George 5 ; Limou Sophie 6 ; Van Natta Mark L 4 ; Jabs, Douglas A 7 ; Estrella, Michelle 8 ; Kopp, Jeffrey B 9   VIAFID ORCID Logo  ; Winkler, Cheryl A 1   VIAFID ORCID Logo 

1  Basic Research Laboratory, Molecular Genetic Epidemiology Section, Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, USA (GRID:grid.418021.e) (ISNI:0000 0004 0535 8394) 
2  Basic Research Laboratory, Molecular Genetic Epidemiology Section, Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, USA (GRID:grid.418021.e) (ISNI:0000 0004 0535 8394); Department of Epidemiology, the Johns Hopkins Bloomberg School of Public Health, Baltimore, USA (GRID:grid.21107.35) (ISNI:0000 0001 2171 9311); Izmir Institute of Technology, Laboratory of Nutrigenomics and Epidemiology, Izmir, Turkey (GRID:grid.419609.3) (ISNI:0000 0000 9261 240X) 
3  Department of Epidemiology, the Johns Hopkins Bloomberg School of Public Health, Baltimore, USA (GRID:grid.21107.35) (ISNI:0000 0001 2171 9311); the Johns Hopkins University School of Medicine, Department of Medicine, Baltimore, USA (GRID:grid.21107.35) (ISNI:0000 0001 2171 9311) 
4  Department of Epidemiology, the Johns Hopkins Bloomberg School of Public Health, Baltimore, USA (GRID:grid.21107.35) (ISNI:0000 0001 2171 9311) 
5  Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Center for Cancer Research Informatics Core, Frederick, USA (GRID:grid.418021.e) (ISNI:0000 0004 0535 8394) 
6  Basic Research Laboratory, Molecular Genetic Epidemiology Section, Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, USA (GRID:grid.418021.e) (ISNI:0000 0004 0535 8394); CRTI UMR1064, Inserm, Université de Nantes & ITUN, CHU Nantes, Nantes, France (GRID:grid.277151.7) (ISNI:0000 0004 0472 0371); Ecole Centrale de Nantes, Nantes, France (GRID:grid.16068.39) (ISNI:0000 0001 2203 9289) 
7  Department of Epidemiology, the Johns Hopkins Bloomberg School of Public Health, Baltimore, USA (GRID:grid.21107.35) (ISNI:0000 0001 2171 9311); the Wilmer Eye Institute, the Johns Hopkins University School of Medicine, Department of Ophthalmology, Baltimore, USA (GRID:grid.21107.35) (ISNI:0000 0001 2171 9311) 
8  University of California San Francisco, Kidney Health Research Collaborative, Department of Medicine, San Francisco, USA (GRID:grid.266102.1) (ISNI:0000 0001 2297 6811); San Francisco VA Health Care System, San Francisco, USA (GRID:grid.429734.f) 
9  Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, USA (GRID:grid.429734.f) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
23993642
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s42003-021-01812-z
ProQuest document ID
2497364005
Copyright
© This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.