Yet, prolonged infection often leads to the emergence of X4-tropic or R5X4-tropic strains in some patients, associated with rapid CD4+ T lymphocyte decline and exacerbated immune function deterioration due to their ability to utilize various host cells for replication and induce stronger apoptotic effects (Koot et al., 1993; Yamashita et al., 1994). Here, CD4 is linked to infection.