Three of these capsid amino acids are predicted to be located in the canyon encircling the fivefold axis of symmetry, one amino acid is found at the fivefold axis of symmetry, and one is located the interior of the capsid. The five EV70 residues define a region of the capsid that controls viral host range, DAF utilization, and cytopathogenicity.Acute hemorrhagic conjunctivitis (AHC) is a viral infection of the eye that was first reported in Ghana in 1969 (5). This highly contagious infection is transmitted through direct or indirect contact with eye secretions. An incubation period of 24 to 48 h is followed by rapid onset of ocular pain, swelling of the eyelids, excessive tearing, pain, and subconjunctival hemorrhage. The disease usually resolves in 3 to 7 days. Enterovirus type 70 (EV70), a member of the Picornaviridae, is one of the etiologic agents of AHC. This recently emerged virus (25) has caused two global AHC pandemics (4, 24), underscoring its highly transmissible nature.EV70 is an unusual enterovirus because AHC is not initiated through the alimentary tract but upon introduction of the virus directly into the eye. The pathogenesis of AHC has not been studied due to lack of a suitable animal model. EV70 has been shown to cause conjunctivitis in the rabbit (21), but little progress has been made with this animal model because there are few immunological reagents or defined mutants available. In humans, paralysis occurs in approximately 1 of 10,000 symptomatic EV70 infections (41). Unlike poliomyelitis, this complication is transient and involves both acute flaccid paralysis of the lower limbs and cranial nerve palsies. The mechanism by which EV70 enters the central nervous system (CNS) and the associated switch from eye to CNS pathogenesis has not been studied.Several mouse models for viral diseases have been established by producing transgenic mice expressing cell receptors for viruses. These animal models have proven valuable for studying the pathogenesis of poliomyelitis (15, 34), measles (3,9,16,28,33), and echovirus paralysis and myocarditis (17). At least one cell receptor for EV70 is decay accelerating factor (DAF), also known as CD55 (19). CD55 is a member of the family of regulators of complement activation and is an important modulator of the complement system (23). Treatment of cells with neuraminidase blocks binding of EV70 (1, 18, 39); however, this effect is not due to removal of sialic acid on CD55. Rather, a second sialylated cell surface protein may be required for EV70 binding. The finding that EV70 can infect human leukocyte cell lines that do not produce CD55 at detectable levels also suggests the presence of a second cell surface receptor for the virus (10).To facilitate genetic analysis of EV70 receptor utilization, the first infectious DNA copy of the EV70 genome was constructed and used to study two strains of the virus with a distinct host range. One virus isolate, EV70-Rmk, replicates in rhesus monkey kidney cells and poorly in HeLa cells and does not cause cytopathic effects. H...