Biological studies of the fusion function of California serogroup Bunyaviruses

Pobjecky, Nadine; Smith, Jonathan; Gonzalez-Scarano, Francisco

Like other enveloped viruses, La Crosse virus is capable of inducing membrane fusion after exposure to mild acid. This function is known to have biological significance at the level of the whole organism, since it has been related to infection in a mouse model. In this report the process of fusion-from-within (FFWI) for LAC and other members of the California serogroup of Bunyaviruses is characterized. Like fusion-from-without, FFWI is dependent on pH, temperature, and number of virus particles present in the supernatant of fusing cells. Electron micrographs demonstrate that LAC mediated cell membrane fusion is a rapid, multi-point event, and that other than fusion of their plasma membranes, the cells do not show any morphological change. In agreement with theory, lysosomotropic agents were capable of inhibiting La Crosse virus infection. This inhibition was not due to non-specific toxic effects on infected cells. Finally, fusion studies of other California serogroup members revealed minor differences in the pH of fusion induction in some strains. These differences were consistent with the known subtyping within the serogroup.