The promoters for human and monkey poliovirus receptors. Requirements for basic and cell type-specific activity

The cellular receptors for poliovirus (PVR) are glycoproteins belonging to the immunoglobulin superfamily. Functional receptors for poliovirus are only expressed by primates; known rodent homologues lack the ability to bind virus due to amino acid differences. Human poliovirus infections are targeted to the gastrointestinal tract and, rarely, to motor neurons in the central nervous system. Available evidence suggests that poliovirus uses only one cellular receptor, implying that the tissue tropism of poliovirus is likely to be related to the expression of the human PVR (hPVR). However, low levels of expression of hPVR-specific mRNAs can be detected in many human tissues other than the apparent target cells. The nonpathogenic function of hPVR is unknown. For a study of the transcriptional control of hPVR expression, we have isolated and characterized the promoter of the hPVR gene. Deletion analysis defined an approximately 280 base pair minimal promoter fragment that: 1) lacks TATA- and CAAT-like elements, 2) is distinguished by a high GC content, and 3) promotes transcription at multiple start sites. The pattern of activity caused by transfection of serial 5'- and 3'-promoter deletions is almost identical in HEp2, HeLa, COS-1, and mouse L929 cells, indicating a similar transcriptional regulation of the hPVR promoter in these cell lines. However, on transfection of Raji cells, a Burkitt's lymphoma cell line harboring a transcriptionally inactive hPVR gene, all promoter reporter constructs tested exerted only residual activity. These results suggest that the cis-element(s) governing cell type-specific hPVR expression resides in the minimal promoter region. We also report the sequences of the promoters of two monkey homologues to hPVR (AGMalpha1 and AGMalpha2). Transcripts encoding the monkey poliovirus receptors originate from a region analogous to that identified for hPVR transcripts.