CD4 and infection: But perhaps the most powerful evidence of the importance of directly antiviral ISGs in HIV-1 pathogenesis comes from the observation that viruses that represent the most likely founder of an individual’s infection, called transmitted/founder (TF) viruses, display a considerably higher resistance to the effects of IFN-I in their replication in primary CD4+ T cells than viruses isolated during the chronic phase (31, 48).