HIV-1-induced cytopathogenicity in cell culture despite very decreased amounts of fusion-competent viral glycoprotein.
In order to examine the potential role of env-induced membrane fusion in the cytopathogenic properties of HIV-1 in cell culture, the effects of mutations within the proteolytic cleavage site of gp160, which result in a reduction but not a complete absence of proteolytic processing have been further studied. Cells expressing the mutant glycoproteins were shown to be severely reduced in their capacity to form syncytia. However, viruses encoding these glycoproteins could infect cell culture cells, albeit with delayed kinetics, and, at late infection time points, resulted in complete cytolysis of the infected culture. Since amplification by polymerase chain reaction and direct sequencing of the DNA in the infected cultures confirmed the presence of the mutant and the absence of revertant DNA, this shows that the amount of fusion competent viral glycoprotein does not influence HIV-1 cytopathogenicity, but rather that other parameters must be involved in inducing cell death.
Bosch
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Forschungsschwerpunkt Angewandte Tumorvirologie, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Pfeiffer
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D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D015686:Gene Products, env / Q000235:genetics / Q000378:metabolism; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D006801:Humans; D008561:Membrane Fusion; D016297:Mutagenesis, Site-Directed; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D014760:Viral Fusion Proteins / Q000235:genetics / Q000378:metabolism*
D015686:Gene Products, env; D019302:HIV Envelope Protein gp160; D011498:Protein Precursors; D014760:Viral Fusion Proteins