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