Functional gene transfer of HIV DNA by an HIV receptor-independent mechanism

HIV-1 enters target cells mainly via binding to CD4 and its coreceptors. Th e presence of HIV-1 in CD4(-) cells suggests, however, that there exist oth er mechanisms for viral entry, Here it is reported that HIV-1 DNA may be tr ansferred from one cell to another by uptake of apoptotic bodies in a CD4-i ndependent way. This was investigated by coculturing CD4(-), chemokine rece ptor CCR5(-) and CXCR4(-) human fetal fibroblasts with apoptotic HIV-1-infe cted HuT78 cells or apoptotic PBMC isolated from HIV-1-infected patients. A fter 2 wk of coculture, fibroblasts contained HIV-1 DNA and expressed HIV-1 proteins p24 and gp120, Transfer of HIV-1 DNA was verified by coculturing fibroblasts with apoptotic bodies derived from cells infected with a defect ive HIV-1 virus. These cells contain one integrated copy of a reverse trans criptase (RT)-negative HIV-1 strain (8E5/LAV RT- cells) and consequently ca nnot produce free virus, Intracellular HIV-1 gag DNA was detected in both f ibroblasts and dendritic cells after coculture with apoptotic 8E5/LAV RT- c ells. Transfer of viral DNA after uptake of apoptotic bodies mag explain HI V-1 infection of CD4(-) cells in vivo and furthermore may be relevant for A g presentation.