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Publications of the Week

Genotypic and Mechanistic Characterization of Subtype-Specific HIV Adaptation to Host Cellular Immunity

By October 25, 2018No Comments

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This week we profile a recent publication in the Journal of Virology from the laboratory of Dr. Zabrina
(pictured, front row 2nd from right) at SFU and the BC Centre for Excellence in HIV/AIDS.

Can you provide a brief overview of your lab’s current research focus?

The Brumme laboratory at SFU and the BC Centre for Excellence in HIV/AIDS integrates molecular biology, epidemiology and computational approaches to examine questions at the interface of HIV virology, immunology and pathogenesis with the ultimate goal of preventing and curing HIV infection.

What is the significance of the findings in this publication?

The identification of specific mutational pathways in HIV that allow the virus to evade host cellular immune responses, and the elucidation of their impact on viral fitness and protein function, can help identify immunogenic viral regions for prophylactic and/or therapeutic vaccine design. However, HIV isolates are extremely genetically variable (the HIV-1 group M “pandemic” isolates can be classified into 9 subtypes and nearly 100 circulating recombinant forms), and our knowledge of immune-driven escape pathways and their functional costs is largely limited to HIV subtype B, and to a lesser extent C. Our study represents the first characterization of immune-driven adaptation pathways in HIV subtypes A1 and D, which dominate in East Africa, and the first statistically rigorous characterization of differential immune-driven escape across viral subtypes. Results support a considerable impact of viral genetic context on HIV adaptation to host immunity, where HIV subtype-specific sequence variation influences both viral epitope presentation and the fitness costs of escape. Integrated bioinformatic and mechanistic characterization of these and other instances of differential escape could aid rational immunogen selection for both subtype-specific and universal HIV vaccines. 

What are the next steps for this research?

We would like to continue to study pathways of HIV adaptation to host immune responses in different HIV-1 subtypes, geographical areas and host populations, with the goal of leveraging this information for vaccine design.

This research was funded by:

A project grant from CIHR.

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