CD4 and infection: HIV-1 can infect CD4+ T cells via two major pathways: (1) cis-infection, a pathway in which cell-free viruses directly infect CD4+ T cells, and (2) trans-infection, where cell-to-cell HIV-1 transmission is mediated by CD4+ T cells or professional antigen-presenting cells (APCs), i.e., myeloid dendritic cells (DCs), monocytes/macrophages, and B lymphocytes (Figure 1).