Mechanistic basis for potent neutralization of Sin Nombre hantavirus by a human monoclonal antibody

Sin Nombre virus (SNV) belonging to Hantaviridae family, is responsible for causing hantavirus cardiopulmonary syndrome, a severe illness associated with high fatality. The transmission of SNV to humans can occur via inhalation of aerosolized excreta from rodent. Gn an Gc, the spike proteins on hantavirus, play an essential role as recognized compartment for antibodies. Prior research suggested that Gn-targeting mAbs potentially enhance neutralization ability against hantavirus. As an effective neutralizing human monoclonal antibody, SNV-42 was isolated from a memory B cell originating from a convalescent SNV donor.  This study aims to evaluate the neutralizing mechanism of SNV-42 through from genetic analysis and protein structure analysis. SNV-42 maintains gene segment which serves a vital part in promoting affinity maturation of antibodies, thereby enhancing antibody specificity. The results of crystallographic analysis on SNV-42 protein binding to SNV Gn protein suggests SNV-42 is capable of interfering with various stages of the viral entry pathway. Subsequently, overlaying SNV-42 and SNV (Gn−Gc) ultrastructure arrangement indicates SNV-42 combine to the distal region of SNV membrane. Furthermore, the researchers conduct a simulation to investigate the interaction between SNV-42 protein and SNV Gn spike protein, suggesting SNV-42 might contribute to receptor blocking and fusion inhibition.

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