CD34+ hematopoietic stem cells support entry and replication of poliovirus: a potential new gene introduction route.

Pluripotent hematopoietic stem cells (HSC) are critical in sustaining and constantly renewing the blood and immune system. The ability to alter biological characteristics of HSC by introducing and expressing genes would have enormous therapeutic possibilities. Previous unpublished work suggested that human HSC co-express CD34 (cluster of differentiation 34; an HSC marker) and CD155 (poliovirus receptor; also called Necl-5/Tage4/PVR/CD155).

Biochemical characterization of the fidelity of poliovirus RNA-dependent RNA polymerase.

Background: Putative high mutation rates of RNA viruses are believed to mediate undesirable phenomena, such as emergence of drug resistance. However, very little is known about biochemical fidelity rates for viral RNA-dependent RNA polymerases. Using a recently developed in vitro polymerase assay for poliovirus polymerase 3Dpol [Arnold and Cameron (2000) JBC 275:5329], we measured fidelity for each possible mismatch.

Conserved aspartic acid 233 and alanine 231 are not required for poliovirus polymerase function in replicons.

Nucleic acid polymerases have similar structures and motifs. The function of an aspartic acid (conserved in all classes of nucleic acid polymerases) in motif A remains poorly understood in RNA-dependent RNA polymerases. We mutated this residue to alanine in a poliovirus replicon.

Fluorescent poliovirus for flow cytometric cell surface binding studies.

Specific cell-surface binding is the essential first step for cellular invasion by viruses. To understand this process, various methods to evaluate binding properties of viruses to cells have been developed. However, many rely on radioactive labeling or indirect immunofluorescence.

Lethal mutagens: broad-spectrum antivirals with limited potential for development of resistance?

RNA virus populations display extreme sequence variation. It is thought that this heterogeneity is advantageous to the population, permitting adaptation to rapidly changing environments that present varying types and degrees of selective pressure. A consequence of this efficient evolution of RNA viruses is the susceptibility of these viruses to compounds that further increase sequence variation as these agents force the virus into error catastrophe.