Meeting report: 30th International Conference on Antiviral Research, in Atlanta, GA, USA

Vere Hodge, R Anthony

During prolonged replication of OPV in immunocompromised subjects, polioviruses can evolve rapidly, the RNA replication error rate being $10 À4 /cycle. In an individual, there are about 1 or 2 base substitutions/ week, giving an overall evolution rate of about 1%/ year. For comparison, this mutation rate is faster than that for HIV, influenza viruses and HCV, viruses generally considered to be rapidly evolving. Most mutations will generate synonymous codons that do not alter the protein coding. However, the few, critical, attenuating mutations in OPV are under negative selection pressure to revert towards the wt. Vaccine-derived polioviruses (VDPVs) have been defined on the basis of threshold divergence in the VP1 capsid protein, There have been a few vaccine-associated paralytic polio cases, about 1-2/1,000,000 (cf. 1/200 from wt virus). Various types of immune deficiency can lead to prolonged virus shedding (>6 months) but severe combined immunodeficiency (SCID) and common variable immunodeficiency (CVID) can result in chronic shedding (>5 years). One individual has been shedding poliovirus for >30 years. Regardless of paralysis status, VDPV in immunodeficient subjects (iVDPV) has been identified as a major threat to polio eradication, especially in those countries that do not have a good medical system. In countries from which poliovirus has been eliminated for many years, the chronic excretors have largely either cleared the virus or died. For example, in the UK there is just one individual alive and still excreting virus after 32 years. In the USA, there may be none remaining, with one potential case lost to follow-up.