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​Santiago and Wilson Labs report on the role of Interferon-α Subtypes in mucosal HIV-1 Infection

Developing therapeutic strategies against HIV/AIDS may require an understanding of the earliest events during HIV-1 infection, which occur predominantly in the gut. These early stages are in part influenced by the host ‘innate’ immune response mediated by the antiviral cytokine, interferon-alpha (IFNα). Recently, IFNα was found to activate ‘restriction factors’– host proteins that can directly inhibit HIV-1. Notably, the therapeutic potential of recombinant IFNα against HIV-1 infection was explored for 25 years, but its effectiveness was inconsistent. However, these clinical trials administered IFNα2, which is only one member of a 12-protein family of IFNα subtypes. To date, it remains unknown which IFNα subtypes are produced by professional IFNα producing cells known as plasmacytoid dendritic cells and which IFNα subtypes are more effective in inhibiting HIV-1 infection in critical target cells in the gut. 

 

      Reporting in PLOS Pathogens (published Nov. 3, 2015), Harper et al. now show that weaker IFNα subtypes were more highly expressed following HIV-1 infection. Using an infection platform that captures important characteristics of HIV-1 infection in the gut, several IFNα subtypes were found to be more effective at inhibiting HIV-1 than IFNα2. In particular, IFNα8 and IFNα14 more potently reduced the infectivity of HIV-1 virions, an activity that can be attributed to the APOBEC3 proteins. The findings strongly support the evaluation of potent IFNα subtypes in currently evolving HIV-1 curative strategies.

 

 

The study was supported by the National Institutes of Health R56 AI116271 (Santiago), R01 108404 (Wilson) and the Department of Medicine Early Career Scholar Program (Santiago). Co-authors include CU Department of Medicine researchers Michael Harper, Kejun Guo, Eric Lee, Stephanie Dillon, Brad Barrett and Martin McCarter.