Cellular compartments of human immunodeficiency virus type 1 replication in vivo: Determination by presence of virion-associated host proteins and impact of opportunistic infection

Antigens derived from host cells are detectable in the envelope of human im munodeficiency virus type 1 (HIV-1) and result in a distinctive viral pheno type reflecting that of the host cell. An immunomagnetic capture assay targ eting discriminatory host proteins was developed to differentiate between H IV-1 derived from macrophages and lymphocytes. HIV-1 propagated in macropha ges or lymphocytes in vitro was selectively captured by monoclonal antibodi es directed against the virally incorporated cell-type-specific host marker s CD36 (macrophages) and CD26 (lymphocytes). Furthermore, by targeting thes e markers, virus of defined cellular origin was selectively captured from a mixed pool of in vitro-propagated viruses. This technique was further refi ned in order to determine the impact of opportunistic infection on HIV-1 ex pression from these cellular compartments in vivo. Analysis of cell-free vi rus purified from plasma of patients with HIV-1 infection suggested that in those with an opportunistic infection, viral replication occurred in activ ated lymphocytes, Interestingly, there was also significant replication in activated macrophages in those patients with untreated pulmonary tuberculos is. Thus, in addition to lymphocytes, the macrophage cellular pool may serv e as an important source of cell-free HIV-1 in patients with opportunistic infections that lead to marked macrophage activation. This novel viral capt ure technique may allow researchers to address a wide range of important qu estions regarding virus-host dynamics.