Deletion of the Cytoplasmic Tail of the Fusion Protein of the Paramyxovirus Simian Virus 5 Affects Fusion Pore Enlargement

Abstract

The fusion (F) protein of the paramxyovirus simian parainfluenza virus 5 (SV5) promotes virus-cell and cell-cell membrane fusion. Previous work had indicated that removal of the SV5 F protein cytoplasmic tail (F Tail؊ or F⌬19) caused a block in fusion promotion at the hemifusion stage. Further examination has shown that although the F Tail؊ mutant is severely debilitated in promotion of fusion as measured by using two reporter gene assays and is debilitated in the formation of syncytia relative to the wild-type F protein, the F Tail؊ mutant is capable of promoting the transfer of small aqueous dyes. These data indicate that F Tail؊ is fully capable of promoting formation of small fusion pores. However, enlargement of fusion pores is debilitated, suggesting that either the cytoplasmic tail of the F protein plays a direct role in pore expansion or that it interacts with other components which control pore growth.

Polybasic KKR Motif in the Cytoplasmic Tail of Nipah Virus Fusion Protein Modulates Membrane Fusion by Inside-Out Signaling

“…6B), we speculate that a step post 6HB formation, perhaps fusion pore enlargement, may be affected by the hypofusogenic mutation R3A. The CT of at least one other paramyxovirus, SV5, has been implicated in fusion pore enlargement (19). Our lipid raft results also highlight the mechanistic differences observed between the hypofusogenic K2A and R3A mutants observed in Fig.…”

“…The CTs of other paramyxovirus fusion proteins are known to be required for various protein functions, including proper surface expression, membrane fusion, fusion pore enlargement, transition from hemifusion to complete fusion, and/or budding (7,19,59,65,68), although removal of the CT has resulted in quite distinct phenotypes in different paramyxoviruses, ranging from no effect (12) to fusion pore formation (65) to fusion pore enlargement (19) to syncytium formation (59,65). In this report, we show that relatively large deletions in the NiV-F CT did not significantly compromise conformational integrity or CSE but can either reduce or enhance fusion (Fig.…”

Roles for the Cytoplasmic Tails of the Fusion and Hemagglutinin-Neuraminidase Proteins in Budding of the Paramyxovirus Simian Virus 5

“…After incubation for 1.5 h, the inocula were removed and the cells were washed three times with PBS. Cultures were grown in 0.5 ml of DMEM supplemented with 2% fetal bovine serum for the following time points: 0, 6,12,18,24,36,48,72, and 96 h p.i. at which point the medium was collected and the titer was determined based on the TCID 50 .…”

“…Previous studies on the fusion characteristics of a cytoplasmic tail-truncated F protein containing only a single charged residue at the transmembrane-cytoplasmic tail domain boundary (F⌬19) showed that the F⌬19 protein exhibited a defect in the expansion of viral fusion pores (12). Thus, one possibility for the altered plaque morphologies for mutant recombinant viruses having severely truncated F protein cytoplasmic tails (Fig.…”

A Y527A mutation in the fusion protein of Newcastle disease virus strain LaSota leads to a hyperfusogenic virus with increased replication and immunogenicity

“…We think that Y527A mutation may increase the interaction of the F protein with viral proteins M and HN, which in turn may modulate the fusion process. For example, in parainfluenza virus 5 F protein, the CT was important in regulating fusion-pore formation (Dutch & Lamb, 2001).The single mutation Y524A seems to have a more pronounced effect on growth kinetics, plaque size and immunogenicity than the double mutation Y524A+Y527A. We predict that the Y524A mutation is located in the transmembrane region of the F protein, which may affect the incorporation of the F protein into the membrane.…”