Specific infection of CD4+ target cells by recombinant rabies virus pseudotypes carrying the HIV-1 envelope spike protein.
A recombinant rabies virus (RV) mutant deficient for the surface spike glycoprotein (G) gene was used to study the incorporation of envelope proteins from HIV-1 expressed from transfected plasmids. A hybrid HIV-1 protein in which the cytoplasmic domain was replaced with that of RV G was incorporated into the virus envelope and rescued the infectivity of the RV mutant. The RV(HIV-1) pseudotype viruses could infect only CD4+ cells, and their infectivity was neutralized specifically by anti-HIV-1 sera. In contrast to the chimeric protein, wild-type HIV-1 envelope protein or mutants with truncated cytoplasmic domains failed to produce pseudotyped particles. This indicates the presence of a specific signal in the RV G cytoplasmic domain, allowing correct incorporation of a spike protein into the envelope of rhabdovirus particles. The possibility of directing the cell tropism of RV by replacement of the RV G with proteins of defined receptor specificity should prove useful for future development of targetable gene delivery vectors.
Mebatsion
T
T
Department of Clinical Virology, Federal Research Centre for Virus Diseases of Animals, Tübingen, Germany.
Conzelmann
K K
KK
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000502:physiology*; D015704:CD4 Antigens / Q000502:physiology*; D017353:Gene Deletion; D015686:Gene Products, env / Q000096:biosynthesis / Q000737:chemistry; D005816:Genetic Complementation Test; D005822:Genetic Vectors; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000737:chemistry; D008969:Molecular Sequence Data; D011820:Rabies virus / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry; D015183:Restriction Mapping; D014616:Vaccinia virus; D014763:Viral Matrix Proteins / Q000096:biosynthesis* / Q000737:chemistry
D015703:Antigens, CD; D015704:CD4 Antigens; D015686:Gene Products, env; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D014763:Viral Matrix Proteins