Abstract
Measles virus (MeV) is monotypic. Live virus challenge provokes a broadly protective humoral immune response that neutralizes all known measles genotypes. The two surface glycoproteins, H and F, mediate virus attachment and entry, respectively, and neutralizing antibodies to H are considered the main correlate of protection. Herein, we made improvements to the MeV reverse genetics system and generated a panel of recombinant MeVs in which the globular head domain or stalk region of the H glycoprotein or the entire F protein, or both, were substituted with the corresponding protein domains from canine distemper virus (CDV), a closely related morbillivirus that resists neutralization by measles-immune sera. The viruses were tested for sensitivity to human or guinea pig neutralizing anti-MeV antisera and to ferret anti-CDV antisera. Virus neutralization was mediated by antibodies to both H and F proteins, with H being immunodominant in the case of MeV and F being so in the case of CDV. Additionally, the globular head domains of both MeV and CDV H proteins were immunodominant over their stalk regions. These data shed further light on the factors constraining the evolution of new morbillivirus serotypes.
Highlights
Morbilliviruses, of the Paramyxoviridae family, are highly infectious respiratory viruses and cause devastating disease in humans and animals
Hybrids of H proteins are expected to stay functional, on the basis of our experience in heterotypic fusion activity when both vaccine strains of Measles virus (MeV) (Edmonston) and canine distemper virus (CDV) (Onderstepoort) were used [42]
The H glycoprotein is a type II integral homotetrameric protein consisting of a large ectodomain structured as a helical stalk and a 6-blade, β-propeller, folded globular head that harbors the receptor-binding site
Summary
Morbilliviruses, of the Paramyxoviridae family, are highly infectious respiratory viruses and cause devastating disease in humans and animals (recently reviewed by Pfeffermann et al [1]). Canine distemper virus (CDV) is a rather promiscuous carnivore morbillivirus, able to infect even primates and cause a disease outbreak [2,3]. This characteristic poses a more than theoretical risk that CDV could extend into the human population after MeV eradication [4,5,6]. The morbillivirus envelope comprises two envelope glycoproteins that encompass the so-called virus fusion-membrane apparatus: the attachment (H) and the fusion (F). F glycoprotein can fuse adjacent cell membranes, forming syncytia when cells expressing H and F interact with cells expressing the receptors [8,9]. Vaccine strains of MeV and CDV have gained the ability to infect other
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