An anti-HIV-1 gp120 antibody expressed as an endocytotic transmembrane protein mediates internalization of HIV-1.
In this study, we used HIV-1 as a model to demonstrate a novel approach for receptor-independent cell entry of virus. The heavy chain of an anti-HIV-1 gp120 antibody was engineered with endocytotic and transmembrane motifs from either the cation-independent mannose 6-phosphate receptor or the low-density lipoprotein receptor. Flow cytometry and immunofluorescence studies showed that the chimeric antibodies were expressed on the cell surface and can undergo rapid internalization. Furthermore, one of the chimeric antibodies was able to bind and internalize HIV-1. Using a luciferase reporter HIV-1, we further showed that internalized viruses could undergo replication. Therefore, we have demonstrated a proof-of-principle of a novel method that can be used to internalize virus into cells, without prior knowledge of the cellular receptor for the virus. We propose that this approach would be particularly useful for studying viruses whose cellular receptor(s) is not known.
Collaborative Anti-Viral Research Group, Institute of Molecular and Cell Biology, 30 Medical Drive, Singapore 117609. mcbtanyj@imcb.nus.edu.sg
Yee-Joo
YJ
Tan
Siew-Pheng
SP
Lim
Anthony E
AE
Ting
Phuay-Yee
PY
Goh
Y H
YH
Tan
Seng-Gee
SG
Lim
Wanjin
W
Hong
D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D004705:Endocytosis; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005803:Genes, Immunoglobulin; D017930:Genes, Reporter; D015483:HIV Antibodies / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000378:metabolism / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins; D008969:Molecular Sequence Data
D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D008565:Membrane Proteins; D008156:Luciferases