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M. P. Chumakov Institute of Poliomyelitis and Viral Encephalitis, Russian Academy of Medical Sciences, Moscow The paper deals with the history of discovery of poliomyelitis virus by K. Landsteiner and E. Popper in 1908, the identification of three immunological types of the virus in 1949, the discovery of viral multiplication in the cultures of non-nerve cells with a cytopathogenic effect by A. Anders in 1949, the development of new diagnostic techniques, the design of inactivated poliovirus vaccine by D. Salk in 1953 and its live vaccine by A. Sabin in 1957. The advantages and disadvantages of these vaccines and the prospects for further poliomyelitis control are discussed. The characteristics and role of nonpoliomyelitis enteroviruses are considered. The most important scientific discoveries made in the study of enteroviruses are noted.

The review presents the currently available data on the receptor specificity of enteroviruses. It discusses whether changes in the receptor specificity of enteroviruses may play a role in their in vitro and in vivo reproduction.

Lines of human-mouse hybrid cells susceptible to infection with poliomyelitis types I, II, III, ECHO type 1 and 12, and Coxsackie A7 viruses have been derived. The presence in the hybrid cells of 2 and 3 genomes of the nonpermissive cell partner (mouse) was shown not to inhibit enterovirus reproduction. Hybrid cultures differed in their sensitivity to the mutagenic action of poliomyelitis virus. There was no correlation between poliomyelitis virus yield and the number of chromosome breaks in hybrid cells. Poliomyelitis virus type I-infected hybrid cultures passaged for 11/2 months eliminated this virus and subsequently became less sensitive to reinfection with poliomyelitis virus of all 3 types but retained their original sensitivity to Coxsackie and ECHO viruses.

Enterovirus type 71 (E71) strains isolated from specimens of the brain and feces of children during an outbreak of poliomyelitis-like infection in Bulgaria in 1975 produce paralytic disease in newborn and adult cotton rats, newborn white mice, and monkeys. By the type of the myo- and neurotropic properties manifested in animal experiments the Bulgarian E71 strains are very close to neuropathogenic strains of Coxsackie A7, A14, and A16 viruses. The infection induced by the Bulgarian E71 strains in green monkeys was by clinical symptoms (tremor, convulsions, death), the speed of the development of the process and the type of morphological lesions particularly similar to the clinical and morphological manifestations of infection observed in most severe cases in children during the outbreak in Bulgaria. Inoculation of newborn and adult cotton rats, newborn white mice and Macaca rhesus monkeys with large doses of the prototype BrCr strain of enterovirus 71 (10(5.0)--10(6) TCD50) caused no clinically manifest disease of the animals.

Strains of poliomyelitis, ECHO-11 and Coxsackie A7 viruses have first been shown to produce uveitis and keratouveitis in Javan macaca and green monkeys inoculated intraocularly. The most marked clinical picture of the eye affection in monkeys (keratoleukoma and opacity of the anterior chamber humor, edema and hyperemia of the iris, significant changes in the iris colour, development of posterior synechias, marked dilation of the pupil to 5-7 mm, no pupil reaction to light) was observed after inoculation with virulent strains of poliomyelitis virus types I, II, and III, and strains of ECHO-11 virus isolated from children with acute infectious uveitis. Uveitis symptoms in monkeys appeared within 20 hours after virus inoculation and persisted for 3 months of observation. No affection of the eyes developed after administration of flaviviruses or control material. In favour of freshly isolated strains of ECHO-11 virus being the cause of uveitis in the children examined are the following facts: ECHO-11 virus was isolated from 5 out of 10 children with uveitis, neutralizing antibody to ECHO-11 virus was found in 8 out of 9 children with uveitis, seven of them showing a rise in antibody titres to ECHO-11 virus to 1:256-1:1024, the clinical picture of uveitis reproduced in monkeys is very similar to that of uveitis in children. The potential role of poliomyelitis viruses and other enteroviruses in the etiology of human uveitis is discussed.

Studies of diabetogenic properties of Coxsackie A13 and B4 viruses in mice sensitive to diabetes (males, DBA line) and resistant (males and females F1(CBA X C57BL/6), females DBA/2 using in the latter case the subdiabetogenic doses of alloxan revealed in the infected animals biochemical changes manifested by reduction of glucose tolerance and disorders in the synthesis of immunoreactive insulin. Most marked changes were observed in males of DBA/2 line infected with Coxsackie B4 virus and in males F1 (CBA X C57BL/6) and females DBA/2 infected with Coxsackie A14 virus. With Coxsackie A13 virus such data have been obtained for the first time.

Virological examinations of 72 specimens obtained during an outbreak of a poliomyelitis-like disease in Bulgaria, 1975, yielded 23 strains of enterovirus type 71 (E71) and 5 strains of enteroviruses of other types. The viruses were isolated in green monkey kidney cell cultures, in newborn cotton rats, newborn white mice and in monkeys. Most of E71 strains (16 out of 23) were isolated from the autopsy materials (brains and spinal cords) from 9 children dying of poliomyelitis, meningoencephalitis, and encephalitis. The remaining E71 strains and all the strains of other enterovirus serotypes, with the exception of ECHO7, were isolated from stool specimens of children with aseptic meningitis and their contacts. The antigenic similarity of the group of Bulgarian strains and their relationship with the prototype BrCr strain of E71 was established. The conclusion is that E71 was the causative agent of an outbreak of a poliomyelitis-like disease in Bulgaria.