Correlation of mutations and recombination with growth kinetics of poliovirus vaccine strains

Attenuated strains of Sabin poliovirus vaccine replicate in the human gut and, in rare cases, may cause vaccine-associated paralytic poliomyelitis (VAPP). The genetic instability of Sabin strains constitutes one of the main causes of VAPP, a disease that is most frequently associated with type 3 and type 2 Sabin strains, and more rarely with type 1 Sabin strains. In the present study, the growth phenotype of eight oral poliovirus vaccine (OPV) isolates (two non-recombinants and six recombinants), as well as of Sabin vaccine strains, was evaluated using two different assays, the reproductive capacity at different temperatures (Rct) test and the one-step growth curve test in Hep-2 cells at two different temperatures (37A degrees C and 40A degrees C). The growth phenotype of isolates was correlated with genomic modifications in order to identify the determinants and mechanisms of reversion towards neurovirulence. All of the recombinant OPV isolates showed a thermoresistant phenotype in the Rct test. Moreover, both recombinant Sabin-3 isolates showed significantly higher viral yield than Sabin 3 vaccine strain at 37A degrees C and 40A degrees C in the one-step growth curve test. All of the OPV isolates displayed mutations at specific sites of the viral genome, which are associated with the attenuated and temperature-sensitive phenotype of Sabin strains. The results showed that both mutations and recombination events could affect the phenotype traits of Sabin derivatives and may lead to the reversion of vaccinal strains to neurovirulent ones. The use of phenotypic markers along with the genomic analysis may shed additional light on the molecular determinants of the reversed neurovirulent phenotype of Sabin derivatives

The international penetration of ibusiness firms: Network effects, liabilities of outsidership and country clout

The burgeoning of ibusiness firms in the modern digital economy challenges the received internationalization theory. Given that ibusinesses such as social networking sites create value by providing a digital platform for users to interact with one another, we employ a user-network perspective and externalization logic, suggesting that ibusinesses’ internationalization process depends critically on users’ collective interactions, instead of being solely driven by firms’ market commitments, as noted by the Uppsala model. However, ibusinesses may suffer from liabilities of outsidership due to the boundedness of international network effects. Drawing on social network theory, we demonstrate that such liabilities can be mitigated by first diffusing the ibusiness platform in countries with higher clout. Our analysis using a unique dataset of mobile ibusiness platforms finds empirical support for the hypotheses. We discuss theoretical implications for the network approach of the Uppsala model in the digital era