Functional Gene Transfer of HIV DNA by an HIV Receptor-Independent Mechanism

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Abstract
HIV-1 enters target cells mainly via binding to CD4 and its coreceptors. The presence of HIV-1 in CD4− cells suggests, however, that there exist other mechanisms for viral entry. Here it is reported that HIV-1 DNA may be transferred from one cell to another by uptake of apoptotic bodies in a CD4-independent way. This was investigated by coculturing CD4−, chemokine receptor CCR5− and CXCR4− human fetal fibroblasts with apoptotic HIV-1-infected HuT78 cells or apoptotic PBMC isolated from HIV-1-infected patients. After 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 defective HIV-1 virus. These cells contain one integrated copy of a reverse transcriptase (RT)-negative HIV-1 strain (8E5/LAV RT− cells) and consequently cannot produce free virus. Intracellular HIV-1 gag DNA was detected in both fibroblasts and dendritic cells after coculture with apoptotic 8E5/LAV RT− cells. Transfer of viral DNA after uptake of apoptotic bodies may explain HIV-1 infection of CD4− cells in vivo and furthermore may be relevant for Ag presentation.