Resistance to type 1 interferons is a major determinant of HIV-1 transmission fitness
Iyer SS., Bibollet-Ruche F., Sherrill-Mix S., Learn GH., Plenderleith L., Smith AG., Barbian HJ., Russell RM., Gondim MVP., Bahari CY., Shaw CM., Li Y., Decker T., Haynes BF., Shaw GM., Sharp PM., Borrow P., Hahn BH.
Significance Effective prevention strategies are urgently needed to control the spread of HIV-1. A critical barrier to developing such strategies is the lack of understanding of the host antiviral defenses that control HIV-1 replication in the mucosa at the site of entry. Here, we characterized viruses from matched donor and recipient pairs to determine whether transmitted HIV-1 strains exhibit traits that increase their transmission fitness. Characterizing 300 limiting dilution-derived isolates, we identified several properties that enhance virus replication in the face of a vigorous innate immune response, of which resistance to type 1 IFNs is the most important. These results provide new insights into the HIV-1 transmission process and define possible new targets for AIDS prevention and therapy.