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.
Spetz
A L
AL
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
Patterson
B K
BK
Lore
K
K
Andersson
J
J
Holmgren
L
L
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