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. 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.
Department of Immunology, Microbiology, Pathology and Infectious Diseases, Division of Infectious Diseases, Center for Genomics Research, Karolinska Institute, Huddinge University, Sweden. anna-lena.spetz@impi.ki.se
A L
AL
Spetz
B K
BK
Patterson
K
K
Lore
J
J
Andersson
L
L
Holmgren
D017209:Apoptosis / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques; D004279:DNA, Viral / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D005347:Fibroblasts / Q000737:chemistry / Q000378:metabolism / Q000821:virology; D018014:Gene Transfer Techniques; D016655:HIV Core Protein p24 / Q000032:analysis; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015728:Receptors, HIV / Q000502:physiology*
D004279:DNA, Viral; D016655:HIV Core Protein p24; D015728:Receptors, HIV