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Functional gene transfer of HIV DNA by an HIV receptor-independent mechanism
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- Spetz, Anna-Lena (author)
- Karolinska Institutet
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- Patterson, Bruce K. (author)
- Northwestern University Medical School, Chicago, USA
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- Lore, Karin (author)
- Karolinska Institutet
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- (creator_code:org_t)
- American Association of Immunologists, 1999
- 1999
- English.
- In: Journal of Immunology. - : American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 163:2, s. 736-742
- Journal article (peer-reviewed)
Abstract
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- 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 mag explain HIV-1 infection of CD4(-) cells in vivo and furthermore may be relevant for Ag presentation.
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