Differential Inhibition of HIV Replication by the 12 Interferon Alpha Subtypes
Alexandra Tauzin, Armando Espinosa Ortiz, Olivia Blake, Calaiselvy Soundaramourty, Charles Joly-Beauparlant, Alexandre Nicolas, Arnaud Droit, Jacques Dutrieux, Jérôme Estaquier, Fabrizio Mammano
Abstract
The initial response against viruses relies in large part on type I interferons, which include 12 subtypes of IFN-α. These cytokines bind to a common receptor on the cell surface and trigger the expression of incompletely overlapping sets of genes. Whether the anti-HIV responses induced by IFN-α subtypes differ in the extent of expression or in the nature of the genes involved remains debated. Also, RNA expression profiles led to opposite conclusions, depending on the importance attributed to the induction of common or distinctive genes. To explore if relevant anti-HIV activities can be differently induced by the IFN-α subtypes, we compared their relative efficacies on specific steps of the replication cycle. We show that the hierarchy of IFN potencies depends on the step analyzed, supporting qualitatively different responses. This work will also prompt the search for novel IFN-induced anti-HIV factors acting on specific steps of the replication cycle.