Three mechanisms of HIV propagation. (A) Cell-free viral transmission. The classical route of viral propagation occurs via the binding of cell-free virions to a permissive host cell via CD4 and viral coreceptors (CCR5 or CXCR4), followed by viral entry into the cytoplasm by fusion and subsequent viral replication. (B) DC–T cell viral transmission. In the mucosal epithelia, DCs capture HIV virions via viral binding to C-type lectin–related (CLR) molecules or other cell-surface receptors, without necessarily becoming infected, and re-present infectious virus to CD4⁺ T cells after migration to the lymph nodes. (C) T cell–T cell viral transmission. An HIV-1–infected CD4⁺T cell infects a second CD4+ T cell without the requirement for release of cell-free virions into the surrounding extracellular milieu, which represents viral propagation through direct cell-to-cell transmission.