CD4 and infection: HIV-1 Env spike is a trimeric glycoprotein comprised of three gp120-gp41 heterodimers which mediate viral attachment, fusion, and entry into CD4+ T cells during cell-free and/or direct cell-to-cell infection [44,89]; however, it has been proposed that only cell-to-cell HIV-1 transmission can overcome deficiencies of viral Env incorporation [44].