Our choice of mucosally transmissible CCR5-tropic viruses for primary and secondary infections was based on the fact that gut-derived CD4+ T cells are the primary targets for CCR5-tropic SHIVs during primary infection [16], [21], [22], and previously published vaccine trials in rhesus macaques showed effective protection after CXCR4-tropic SHIV challenge but difficulty in containment of CCR5-tropic SIV/SHIV infection [23]–[25]. This evidence concerns the gene CD4 and infection.