Initially revealed using HIV-1 strains expressing CCR5-using M-tropic viral envelopes, we have recently showed that primary viral variants isolated from infected patients, using either CCR5 and/or CXCR4 and characterized by cell-free infection assays as non-M tropic, including some R5-tropic T/F viruses, can be efficiently transferred from infected T cells and then disseminate in macrophages through cell–cell fusion, resulting in the formation of productively infected MGCs [89]. This evidence concerns the gene CXCR4 and infection.