ISOLATION OF THE HUMAN PC6 GENE ENCODING THE PUTATIVE HOST PROTEASE FOR HIV-1 GP160 PROCESSING IN CD4(-LYMPHOCYTES() T)

Production of infectious HIV-1 virions is dependent on the processing of envelope glycoprotein gp160 by a host cell protease, The protease i n human CD4(+) T lymphocytes has not been unequivocally identified, ye t members of the family of mammalian subtilisin-like protein convertas es (SPCs), which are soluble or membrane-bound proteases of the secret ory pathway, best fulfill the criteria. These proteases are required f or proprotein maturation and cleave at paired basic amino acid motifs in numerous cellular and viral glycoprotein precursors, both in vivo a nd in vitro, To identify the gp160 processing protease, we have used r everse transcription-PCR and Northern blot analyses to ascertain the s pectrum of SPC proteases in human CD4(+) T cells. We have cloned novel members of the SPC family, known as the human PC6 genes, Two isoforms of the hPC6 protease are expressed in human T cells, hPC6A and the la rger hPC6B, The patterns of SPC gene expression in human T cells has b een compared with the furin-defective LoVo cell line, both of which ar e competent in the production of infectious HIV virions, This comparis on led to the conclusion that the hPC6 gene products are the most like ly candidates for the host cell protease responsible for HIV-1 gp160 p rocessing in human CD4(+) T cells.