The zoonotic potential of sialic acid-binding paramyxoviruses: viral determinants of host tropism

Abstract

Animal viruses can cause zoonotic outbreaks when they acquire adaptations that enable them to infect and transmit between humans. Several spillover events have already been described or proposed for paramyxovirus species. In particular, henipaviruses have caused repeated, highly lethal zoonotic infections in humans. Paramyxoviruses with a haemagglutinin-neuraminidase (HN) protein as attachment protein bind specific oligosaccharides with terminal sialic acid residues, similar to influenza viruses. Especially members of the HN-bearing Orthorubulavirus and Respirovirus genus, which have a broad mammalian host range and already include important human pathogens, might spill over to human hosts. Viruses similar to the human-specific orthorubulaviruses mumps virus and human parainfluenza virus 4 have already been found in bats, suggesting that these viruses have a zoonotic origin. Viruses need to interact with many host proteins during their replication cycle and the viral host range is largely determined by the ability of viruses to adapt to the proteome and glycome of different species. While some key adaptations for zoonotic spillover have been identified for influenza viruses, not much is known about the mutations and interactions important for paramyxovirus zoonosis. Compared to influenza viruses, changes in receptor specificity seem to be less important for HN-bearing paramyxoviruses. While influenza viruses usually need to change their receptor specificity from α2,3-linked to α2,6-linked sialic acid to become human pathogens, animal and human HN-bearing paramyxoviruses have similar specificities and preferentially bind α2,3-linked sialic acid. Although receptor binding is one of the most important determinants of cell and host tropism, other virus-host interactions may also need to change when viruses spill over to new hosts. These interactions could be required for processes such as viral RNA synthesis, innate immune evasion and virion release and transmission. Future research is required to identify the most important host range barriers for paramyxoviruses. Screening of important paramyxovirus reservoirs in combination with phenotypical characterization of new viruses could help to assess the zoonotic threat of animal paramyxoviruses.