As in any reconstitution attempt of complex biological processes, this prototype model system does not recapitulate all aspects relevant to HIV-1 spread in an infected individual as it lacks, e.g., adaptive and cellular immune responses with their corresponding cytokine milieus, does not reflect the precise tissue architecture and cell heterogeneity/density characteristic for individual target organs, and relies on non-physiological activation stimuli to render CD4 T cells permissive to HIV-1 infection. The gene discussed is CD4; the disease is HIV-1 infection.