Inactivation of a range of viruses, such as adeno-, mumps, rota-, polio- (types 1 and 3), coxsackie-, rhino-, herpes simplex, rubella, measles, influenza and human immunodeficiency viruses, by povidone-iodine (PVP-I) and other commercially available antiseptics in Japan was studied in accordance with the standardized protocol in vitro. In these experiments, antiseptics such as PVP-I solution, PVP-I gargle, PVP-I cream, chlorhexidine gluconate, alkyldiamino-ethyl-glycine hydrochloride, benzalkonium chloride (BAC) and benzethonium chloride (BEC) were used. PVP-I was effective against all the virus species tested. PVP-I drug products, which were examined in these experiments, inactivated all the viruses within a short period of time. Rubella, measles, mumps viruses and HIV were sensitive to all of the antiseptics, and rotavirus was inactivated by BAC and BEC, while adeno-, polio- and rhinoviruses did not respond to the other antiseptics. PVP-I had a wider virucidal spectrum, covering both enveloped and nonenveloped viruses, than the other commercially available antiseptics.

A number of recombinants between the virulent Mahoney and attenuated Sabin strains of type 1 poliovirus were constructed by using infectious cDNA clones of the two strains. To identify a strong neurovirulence determinant(s) residing in the genome region upstream of nucleotide position 1122, these recombinant viruses were subjected to biological tests, including monkey neurovirulence tests. The results of the monkey neurovirulence tests suggested the important contribution of an adenine residue (Mahoney type) at position 480 to the expression of the neurovirulence phenotype of type 1 poliovirus. This nucleotide, however, had only a minor effect, if any, on viral temperature sensitivity. Monkey neurovirulence tests on the recombinant virus whose genome had a guanine residue (Sabin type) at position 480 and variants generated from this recombinant virus in the central nervous system of monkeys strongly suggested that only one nucleotide change, from adenine to guanine, was not sufficient for full expression of the attenuation phenotype encoded by this genome region. These results suggest that the expression of the attenuation phenotype depends on the highly ordered structure formed in the 5' noncoding sequence and that the formation of such a structure is possibly influenced by the nucleotide at position 480. Furthermore, in vitro biological tests performed on viruses recovered from the central nervous system of monkeys injected with a temperature-sensitive recombinant virus showing the small-plaque and d phenotypes revealed that most of the recovered viruses had even higher temperature sensitivities and that all of the recovered viruses that had acquired the large-plaque phenotype had lost the d phenotype to some extent. These results indicate that there may be an unknown selection pressure(s) in the central nervous system and that common determinants might be involved in the expression of the small-plaque and d phenotypes.

Mutations have been identified in variants of poliovirus, type 1 (Mahoney) on the basis of their resistance to neutralization by individual monoclonal antibodies. The phenotypes of these variants were defined in terms of antibody binding; the pattern of epitopes expressed or able to be exploited for neutralization were complex. Single amino acid changes can have distant (in terms of linear sequence) and generalized effects on the antigenic structure of poliovirus and similarly constituted virions.

Poliovirus exists as three stable serotypes (PV-1, PV-2, and PV-3). These viruses display three antigenic sites each, designated N-AgI, N-AgII, and N-AgIU. When mice are immunized with poliovirus, N-AgI is the major neutralization antigenic site for PV-3, whereas N-Agl and N-AgHI are immunodominant over N-AgI for PV-1. To study the relationship between structure and antigenicity, a hybrid virus was constructed in which N-AgI of PV-1 was replaced by N-AgI of PV-3. PV-3-and PV-1-specific antisera, including those elicited by PV-3 in primates, neutralized the hybrid virus. Injection of the hybrid virus into rabbits or into primates resulted in the production of antisera that neutralized both PV-1 and PV-3. The data show that sequence replacement at N-AgI of poliovirus is compatible with viral proliferation, an observation useful for the development of multivalent picornavirus vaccines.