Multiple rotavirus species encode fusion-associated small transmembrane (FAST) proteins with cell type-specific...

Area of Science:

• Virology
• Cell Biology
• Structural Biology

Background:

• Fusion-associated small transmembrane (FAST) proteins are viral proteins crucial for mediating cell-cell fusion and forming syncytia.
• Previous research identified human species B rotavirus NSP1-1 as a FAST protein inducing syncytia in primate cells but not rodent cells.
• The host specificity of NSP1-1 proteins across different rotavirus species remained largely unexplored.

Purpose of the Study:

• To investigate whether NSP1-1 proteins from various rotavirus species can mediate cell-cell fusion.
• To determine if the cell-type specificity of NSP1-1 fusion activity is conserved across different rotavirus species.
• To identify the specific protein domains responsible for the cell-specific fusion activity of human species B rotavirus NSP1-1.

Main Methods:

• Bioinformatic prediction of NSP1-1 protein structures and domain organization for species B, G, and I rotaviruses.
• Transient expression of NSP1-1 proteins in a diverse range of cell types, including avian, canine, hamster, human, porcine, and simian.
• Engineering chimeric FAST proteins by exchanging domains between rotavirus NSP1-1 and orthoreovirus p10 to map functional domains.

Main Results:

• NSP1-1 proteins from rotavirus species B, G, and I consistently induced syncytia in primate cells, irrespective of their viral host origin.
• Fusion activity was limited in non-primate cell types, and this limitation could not always be explained by protein expression levels or RNA stability.
• The N-terminal and transmembrane domains of human species B rotavirus NSP1-1 were identified as key determinants of its cell-specific fusion activity.

Conclusions:

• Rotavirus species B, G, and I NSP1-1 proteins function as FAST proteins capable of mediating cell-cell fusion.
• The N-terminal domains of these NSP1-1 proteins play a significant role in specifying the target cell types for syncytium formation.
• These findings offer insights into viral host range determinants and the functional plasticity of FAST proteins, potentially impacting therapeutic strategies and understanding virus epidemiology.