The human poliovirus receptor. Receptor-virus interaction and parameters of disease specificity.
The host range of poliovirus is determined by the expression of the hPVR, a member of the immunoglobulin superfamily. We characterized hPVR proteins biochemically and found them to be complex-type glycoproteins. The outermost V-like domain of three extracellular domains harbors the PVR function. A panel of single or multiple amino acid exchanges were introduced throughout this domain in order to localize regions involved in virus-receptor interactions. Putative contact amino acids were found to reside in the C'C"D and DE regions. Binding and uptake of poliovirus paralleled virus replication in all mutants tested suggesting that virus binding was affected without abrogating the ability to mediate subsequent events in the infection. Although the primate PVR is essential in conferring susceptibility to poliovirus infection, certain strains can induce neurological disease in rodents. Mouse neurovirulent PV isolates of divergent serotypical origin each provoked a distinctive, characteristic neurological syndrome upon intracerebral infection of wild-type mice. We analyzed clinical and histopathological features of diffuse encephalomyelitis caused by these PV strains and compared the condition with poliomyelitis in mice transgenic for the hPVR. Diffuse PV encephalomyelitis in wild-type mice could be distinguished clinically and histopathologically from hPVR-mediated poliomyelitis in trangenic mice. We localized the determinants of mouse neurovirulence of PV1(LS-a), a derivative of PV1 (Mahoney), in a portion of the viral genome encompassing parts of the capsid protein VP1 as well as the nonstructural protein 2A. Mouse neuropathogenicity could possibly be conferred by reduced particle stability of PV1(LS-a) inasmuch as we found particles to be thermolabile.
Gromeier
M
M
Department of Microbiology, School of Medicine, State University of New York at Stony Brook 11794-8621, USA.
Lu
H H
HH
Bernhardt
G
G
Harber
J J
JJ
Bibb
J A
JA
Wimmer
E
E
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D006801:Humans; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011051:Poliomyelitis / Q000473:pathology / Q000503:physiopathology*; D017955:Poliovirus / Q000502:physiology*; D011489:Protein Denaturation; D017434:Protein Structure, Tertiary; D011991:Receptors, Virus / Q000737:chemistry / Q000502:physiology*; D013329:Structure-Activity Relationship
D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011991:Receptors, Virus; C066100:poliovirus receptor