Perelygina L, Chen MH, Suppiah S, et al. - In this work, researchers described four primary immune deficiencies (PID) patients from whom isolation of infectious immunodeficiency-related vaccine-derived rubella viruses (iVDRV) from the skin biopsies collected at different times after vaccination was done. Full genomic sequences of these iVDRV were ascertained and the changes relative to the parental RA27/3 virus were portrayed with the purpose of identifying the RA27/3 evolution during persistent infection in PID patients. The duration of persistence seemed to influence the degree of divergence of each iVDRV; this indicates continuous intrahost evolution. Based on mutational spectra and signatures, they suggest a major role for APOBEC cytidine deaminases and a secondary role for ADAR adenosine deaminases in producing diversity of iVDRVs. They noted higher quasispecies diversity in granulomas than in recovered infectious iVDRVs. Complete reversion to wild type phenotype was not identified in any of the iVDRV isolates but differences were noted in replicative and persistence characteristics of iVDRVs from those of the RA27/3 vaccine strain; this creates difficulties in predictions of iVDRV transmissibility and teratogenicity. However, the discovery of iVDRV RNA in nasopharyngeal specimen and inadequate neutralization of some iVDRV strains by sera from vaccinated persons implies possible public health hazards correlated with iVDRV carriers. The suggested marker of virus persistence was the detection of IgM antibody to rubella viruses; this was observed in sera of two out of three patients and may assist in identifying patients with iVDRV before development of lesions.