Interferon-α Subtypes in an Ex Vivo Model of Acute HIV-1 Infection: Expression, Potency and Effector Mechanisms

• DOI: 10.1371/journal.ppat.1005254
• Publication Date: 2015-11-03T13:58:09Z
• Authors: Michael S. Harper; Kejun Guo; Kathrin Gibbert; Eric J. Lee; Stephanie M. Dillon; Bradley S. Barrett; Martin D. McCarter; Kim J. Hasenkrug; Ulf Dittmer; Cara C. Wilson; Mario L. Santiago
• Keywords: Ex vivo; Infectivity; Tetherin; Interferon type I; APOBEC3G

HIV-1 is transmitted primarily across mucosal surfaces and rapidly spreads within the intestinal mucosa during acute infection. The type I interferons (IFNs) likely serve as a first line of defense, but relative expression antiviral properties 12 IFNα subtypes against infection tissues remain unknown. Here, we evaluated all in HIV-1-exposed plasmacytoid dendritic cells by next-generation sequencing. We then determined potency each subtype ex vivo using human Lamina Propria Aggregate Culture model. transcripts from centromeric half IFNA gene complex were highly expressed pDCs following exposure. There was an inverse relationship between potency. IFNα8, IFNα6 IFNα14 most potent restricting IFNα2, clinically-approved subtype, IFNα1 both exhibited relatively weak activity. potencies correlated with binding affinity to IFN receptor induction levels restriction factors Mx2 Tetherin/BST-2 not APOBEC3G, F D. However, despite lack APOBEC3 transcriptional induction, higher IFNα8 stronger inhibition virion infectivity, which linked deaminase-independent By contrast, (IFNα8) (IFNα1) significantly induced GG-to-AG hypermutation. results unravel non-redundant functions infection, strong implications for immunity, viral evolution IFNα-based functional cure strategies.