An investigation of the genetic basis of increased susceptibility to neutralization by anti-fusion glycoprotein antibody arising on passage of human respiratory syncytial virus in cell culture.

Human respiratory syncytial virus isolates have previously been shown to exhibit resistance to neutralization by anti-fusion glycoprotein antibodies that is lost on passage in cell culture. Early passage resistant and late passage susceptible stocks of two virus isolates from different epidemics were cloned by plaque purification. Early passage stocks of both isolates yielded predominantly neutralization resistant clones while late passage stocks yielded predominantly susceptible clones. On further characterization of resistant and susceptible clones, resistant virus yields were lower and they were relatively resistant to both neutralization and fusion inhibition by anti-F murine monoclonal antibodies and were also resistant to neutralization by human sera and by Palivizumab. The full genome of resistant and susceptible clones from one of the isolates was sequenced. Four differences, confirmed by sequencing sister clones, were found between resistant and susceptible clones, one in each of the SH, G, F, and L genes.

A radical form of nitric oxide suppresses RNA synthesis of rabies virus.

Hydrophobia is an incurable disease of the central nervous system. Therefore, every mode of the immune response is important to inhibit and clear infection. Innate immunity such as nitric oxide is significantly upregulated during rabies virus infection in vivo. In this report, the possible role of nitric oxide in inhibition of rabies virus replication was studied. Rabies virus infected neuroblastoma cells were treated with nitric oxide generated from SNP or SNP in the presence of ascorbate. SNP-ascorbate generates mainly NO* in culture medium while NO(+) is the major product of SNP alone. Treatment with SNP-ascorbate resulted in delay and suppression of infectious viral particle production. In contrast, treatment with SNP alone did not interfere with multiplication of this virus. The mechanism of inhibition by NO was at the level of gene expression, which was demonstrated by reduction in the level of N, G and L gene expression. The effect of SNP-ascorbate generated NO on rabies virus protein synthesis was also investigated. Synthesis of N protein in the presence of NO was suppressed which correlated to down regulation of N gene expression. We hypothesize that one of the roles of NO in the central nervous system during rabies virus infection is to limit viral dissemination by down-regulating rabies virus production through transcription inhibition.