Summary auto-generated
This study demonstrates that wild-type rinderpest virus (RPV), a morbillivirus related to measles virus, uses SLAM (CD150) as its primary cellular receptor, while cell culture-adapted vaccine strains have evolved to use heparan sulfate as an alternative receptor. Using recombinant virus technology with the virulent Kabete O (KO) strain and the attenuated Plowright vaccine strain, the researcher identified the viral hemagglutinin (H) protein as responsible for receptor specificity. Wild-type KO virus infected cells efficiently only when SLAM was present, whereas the vaccine strain RBOK infected both SLAM-expressing and heparan sulfate-expressing cells. Domain swapping experiments showed that the carboxyl-terminal globular head of the H protein contains the SLAM-binding domain. Four amino acid changes in the H protein (T496I, R556K, I586V, E603K) were identified as enabling heparan sulfate binding, with the E603K mutation appearing particularly important for acquiring SLAM-independent infectivity. These findings parallel receptor adaptation mechanisms observed in other viruses and suggest that tissue culture adaptation in RPV involves selection for heparan sulfate-binding variants, similar to what occurs with measles virus and CD46.
Key findings
- Wild-type rinderpest virus requires SLAM (CD150) as a cellular receptor for efficient infection of lymphoid cells, while cell culture-adapted vaccine strains use heparan sulfate as an alternative receptor
- The viral hemagglutinin (H) protein determines receptor specificity, with the carboxyl-terminal globular head containing the SLAM-binding domain
- Four specific amino acid substitutions in the H protein (particularly E603K) enable the transition from SLAM-dependent to heparan sulfate-dependent infection during cell culture adaptation
- Wild-type RPV grows poorly in epithelial cells but efficiently in lymphoid cells expressing SLAM, reflecting the natural lymphotropic nature of the virus
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Abstract
Rinderpest virus (RPV) is a morbillivirus, related closely to the human pathogen Measles virus (MV). Although cell culture-adapted strains of RPV can infect many kinds of cell from different hosts, one such strain has previously been shown to have a detectable preference for cells expressing the MV receptor CD150 (SLAM), a protein found only on certain types of activated T cells, B cells and dendritic cells. Here, it is shown that the wild-type, virulent parent of the most common vaccine strain of RPV requires CD150 as a receptor, whilst the cell culture-adapted vaccine strain has acquired the ability to use heparan sulphate as an alternative receptor.