Innovative analytics to help protect against HIV
HIV peptidome-wide association study reveals patient-specific epitope repertoires associated with HIV control. Arora J, McLaren PJ*, Chaturvedi N, Carrington M, Fellay J, Lenz TL. Proc Natl Acad Sci U S A. 2019 Jan 15;116(3):944-9. doi: https://doi.org/10.1073/pnas.1812548116. Epub 2019 Jan 2. PMID: 30602460
This collaborative publication examines the development of an innovative computational approach to identify therapeutic targets for the prevention and control of HIV/AIDS. The NML plays a valuable leadership role in protecting Canadians from sexually transmitted and blood-borne infections (STBBI) and supports the uptake of modern innovative technologies to reduce the burden of HIV/AIDS. The NML undertakes many activities to help reduce the spread and public health impact of this infectious disease, and our various activities align with federal and global Initiatives to address HIV/AIDS, for example, the Canadian Federal Initiative, the Federal STBBI Framework, and the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets.
What was known about this area prior to your work, and why was the research done?
An allele is a variant form of a gene that can affect an organism’s health outcome. The severity of HIV can be strongly influenced by the Human Leukocyte Antigen (HLA) class I family of genes. While some alleles provide strong protection against HIV, others are associated with rapid disease progression. The full complement of HIV viral protein sequences (i.e., epitopes) and their relation with HIV-protective/increased risk HLA alleles are technically challenging to examine through traditional lab-based assays due to the large number of possible HLA/epitope combinations. In order to overcome this technical challenge, we developed a computational method to predict allele/epitope interactions from viral sequences. Further, we were able to test which epitopes most strongly correlate with HIV-protective or increased risk alleles.
What are your most significant findings from this work?
While previous studies have identified several HIV epitopes from HLA class I family of genes resulting in either HIV-protection or increased HIV risk, not all HLA allele/epitope combinations have been exhaustively tested or described. By simulating these interactions computationally, we were able to demonstrate that the majority of epitopes associating with HIV protection mapped to the envelope gene (env), with a smaller but substantial contribution by epitopes in the virulence infectivity factor (vif) and group specific antigen (gag) genes. By focusing on env and gag, we identified a large number of previously undescribed epitope/HLA combinations that are associated with protection against HIV. These finding can greatly impact potential therapeutic and vaccine targets for HIV.
What are the implications or impact of the research?
Our new computational method allows for the identification of specific epitopes associated with HIV-protective HLA alleles. This information is very important in the development of HIV therapeutics and vaccines, and has the potential to accelerate the development of targeted and/or more effective treatments to decrease HIV viral load in infected patients. Globally, suppressing HIV viral load in HIV infected individuals is a key strategy to eradicate HIV spread, as stated by UNAIDS. Our computational method and research findings provide additional information to approach and address the public health impacts of HIV/AIDS.
Additional References of Significance:
- McLaren PJ*, et al. Polymorphisms of large effect explain the majority of the host genetic contribution to variation of HIV-1 virus load. Proc Natl Acad Sci USA 2015 Nov 24; 112:14658–63. doi: https://doi.org/10.1073/pnas.1514867112
- Bartha I, et al. A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control. Elife 2013 Oct 29; 2:e01123. doi: https://doi.org/10.7554/eLife.01123
- Date modified: