SIGNIFICANCE OF MACROPHAGE TROPISM OF SIV IN THE MACAQUE MODEL OF HIVDISEASE

Microglia, alveolar macrophages, and Langerhans cells are representati ves of cells of macrophage lineage that are susceptible to infection w ith HIV-1 and they play important roles in the pathogenesis of AIDS de mentia, lymphoid interstitial pneumonia, and systemic viral invasion f rom mucosal surfaces, respectively, In contrast, elimination of CD4(+) T cells with resultant development of immunosuppression and AIDS is t hought to be reflective of the exclusive tropism of the virus for CD4( +) T cells, Examination of these concepts in macaques infected with mo lecularly cloned strains of SIVmac suggested that all strains of the v irus are both macrophage- and lymphocyte-tropic and that all aspects o f pathogenesis including loss of CD4(+) T cells are dependent on infec tion in both cell types, However, viral clones that caused productive lytic infection in macrophages were less virulent than those which cau sed persistent nonproductive infection, The former caused subclinical and even immunizing infections, whereas the latter caused activation a nd productive infection in CD4(+) T cells, AIDS, and systemic infectio n, even after inoculation of the virus on mucosal surfaces. If these f indings on SIVmac are relevant to HIV-1 disease, then demonstration th at HIV-1 isolates are macrophage-tropic probably does not necessarily correlate with their pathogenic potential.