Mutational Analysis of Measles Virus Suggests Constraints on Antigenic Variation of the Glycoproteins

Abstract

Summary Measles virus undergoes error-prone replication like other RNA viruses, but over time it has remained antigenically monotypic. The constraints on the virus that prevent the emergence of antigenic variants are unclear. As a first step in understanding this question, we subjected the measles virus genome to unbiased insertional mutagenesis and viruses that could tolerate insertions were rescued. Only insertions in the nucleoprotein, phosphoprotein, matrix protein, as well as intergenic regions were easily recoverable. Insertions in the glycoproteins of measles virus were severely under-represented in our screen. Host immunity depends on developing neutralizing antibodies to the hemagglutinin and fusion glycoproteins; our analysis suggests that these proteins occupy very little evolutionary space and therefore have difficulty changing in the face of selective pressures. We propose that the inelasticity of these proteins prevents the sequence variation required to escape antibody neutralization in the host, allowing for long-lived immunity after infection with the virus.

Future research to underpin successful peste des petits ruminants virus (PPRV) eradication

“…Future research should therefore focus on insuring against such an eventuality. One option is to concentrate analysis on the ectodomain region of the H ORF, as is the case for MeV [73], since these data can also be translated into functional information on receptor binding [74] or antigenicity [75], while still providing sufficient data to cluster the viruses phylogenetically along similar lines to the existing N-and F-based systems (Fig. 3).…”

Deconstructing the Antiviral Neutralizing-Antibody Response: Implications for Vaccine Development and Immunity

“…For example, due to a lack of significant antigenic drift, there has not been a need to reformulate the monovalent YFV 17D vaccine, even after 60ϩ years of use (195). Many factors may modulate viral antigenic evolution, including differences in virus host range (196) and the inherent mutational tolerance of virus surface glycoproteins (197,198).…”

Morbillivirus Experimental Animal Models: Measles Virus Pathogenesis Insights from Canine Distemper Virus

“…Morbillivirus vaccines have so far retained their efficacy, since the antigenic stability of these viruses is remarkably high compared to other RNA viruses, likely due to constraints on their glycoproteins [72]. Nonetheless, the development of a new generation of vaccines is actively ongoing to explore the potential of morbilliviruses as vaccine platforms, and, in the case of CDV, to increase safety for highly sensitive species.…”