UNDERSTUDIED EMERGING PARAMYXOVIRUSES: FROM PATHOGENICITY TO CELL-CELL FUSION AND VIRAL ENTRY MECHANISMS

Abstract

The family Paramyxoviridae has a wide host range and includes viruses with high potential to induce future epidemics and pandemics. Two genera of the family, Morbillivirus and Henipavirus, include many pathogenic viruses. Feline morbillivirus (FeMV) and Mojiang virus (MojV) are two recently identified viruses in these genera, respectively. FeMV was firstly isolated from an infected stray cat in Hong Kong in 2012. Since its first detection, many strains with genetic diversity have been found worldwide. Although previous studies determined some of its characteristics, such as in vitro host range and clinical signs of FeMV-infected cats, further studies are still needed. For instance, FeMV’s tropism and viral entry mechanisms are still unknown, and its association with several feline kidney diseases is controversial. MojV is the first rat-originated henipavirus identified in China in 2012. The host cell receptor(s) of the MojV G is still undetermined, and its amino acid identity with other bat-originated henipaviruses is only 20%. Despite its uniqueness, our experimental data suggest that the G proteins of MojV and another deadly pathogenic henipavirus, Nipah (NiV), can complement each other, which confirms that MojV belongs to the genus Henipavirus. Our study results also showed that the three cysteines on the MojV G stalk domain are involved in many roles in cell-cell fusion and viral entry into host cells. Furthermore, the two surface glycoproteins of MojV, G and the fusion protein (F), are far less N-glycosylated than those of other henipaviruses. Different from MojV F whose two N-glycans were involved in F protein expression, proteolytic F2 cleavage, fusogenic capability, and viral entry levels, the sole N-glycan on the G protein did not show any roles, suggesting that N-glycosylation on MojV G only plays minor roles in modulating cell-cell fusion and viral entry mechanisms. My study highlights the two understudied emerging viruses and expands knowledge on membrane fusion and viral entry mechanisms amongst paramyxoviruses.