AIDSWEEKLY Plus, Monday, 18 August 1997
Daniel J. DeNoon, Senior Editor
An RNA virus engineered to express the HIV-1 gp120 envelope glycoprotein can be used to deliver gene therapies or as a possible AIDS vaccine.
Yale University researchers J. Erik Johnson et al. found a way to get recombinant vesicular stomatitis virus (VSV) to express the HIV-1 envelope: they removed the large cytoplasmic portion of the gp41 glycoprotein and replaced it with the cytoplasmic domain of the VSV transmembrane glycoprotein.
Extra transcription units also engineered into the recombinant VSV resulted in stable, replication competent viruses capable of high-level expression of HIV-1 proteins.
"Our results illustrate that it is possible to express functional HIV envelopes from the VSV genome and target the recombinant virus to an alternative receptor," Johnson et al. wrote. "The recombinants may also prove useful as HIV vaccines."
Johnson et al. reported their findings in the Journal of Virology ("Specific Targeting to CD4(+) Cells of Recombinant Vesicular Stomatitis Virus Encoding Human Immunodeficiency Virus Envelope Proteins," J Virol, 1997;71:5060-8).
The envelopes of the recombinant VSV expressed properly processed HIV-1 gp120 on the cell surface. Both laboratory and primary isolates of HIV-1 were used to create the VSV recombinants.
When cell-recognition elements on the VSV recombinants were neutralized with anti-VSV antibodies, the recombinants could infect only HeLa cells expressing CD4. Addition of anti-HIV antibodies abolished this ability to infect CD4(+) cells.
Of possible concern is that the anti-VSV-treated VSV recombinants expressing gp120 from wild-type HIV-1 strains were 100-fold less infectious for the CD4(+) cells than were recombinants expressing gp120 from laboratory strains.
The corresponding author for this study is J. Erik Johnson, Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06510.
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