Canine Distemper Viruses Expressing a Hemagglutinin without N-Glycans Lose Virulence but Retain Immunosuppression

Sawatsky, Bevan; Messling, Véronika von

doi:10.1128/jvi.01813-09

Cited by 57 publications

(49 citation statements)

References 56 publications

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“…We noticed a difference in the electrophoretic mobility between Hwt and HOP, very likely resulting from alternative processed N-glycosylation sites (Fig. 1A) (21). Moreover, it appeared that total expression of HOPeF was substantially reduced compared to that of HwteF and HSBeF, thus suggesting some defects in protein stability and/or accelerated degradation.…”

mentioning

confidence: 92%

Identification of Key Residues in Virulent Canine Distemper Virus Hemagglutinin That Control CD150/SLAM-Binding Activity

Zipperle¹,

Langedijk

Örvell

et al. 2010

J Virol

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Morbillivirus cell entry is controlled by hemagglutinin (H), an envelope-anchored viral glycoprotein determining interaction with multiple host cell surface receptors. Subsequent to virus-receptor attachment, H is thought to transduce a signal triggering the viral fusion glycoprotein, which in turn drives virus-cell fusion activity. Cell entry through the universal morbillivirus receptor CD150/SLAM was reported to depend on two nearby microdomains located within the hemagglutinin. Here, we provide evidence that three key residues in the virulent canine distemper virus A75/17 H protein (Y525, D526, and R529), clustering at the rim of a large recessed groove created by ␤-propeller blades 4 and 5, control SLAM-binding activity without drastically modulating protein surface expression or SLAM-independent F triggering.

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mentioning

confidence: 92%

Identification of Key Residues in Virulent Canine Distemper Virus Hemagglutinin That Control CD150/SLAM-Binding Activity

Zipperle¹,

Langedijk

Örvell

et al. 2010

J Virol

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“…The extent of PBMC proliferation inhibition was assessed by stimulation of Ficoll-purified PBMC with 1 g/ml phytohemagglutinin (PHA) and subsequent detection of bromodeoxyuridine (BrdU) incorporation into proliferating cells by use of a cell proliferation BrdU enzyme-linked immunosorbent assay (ELISA) kit (Roche). Wild-type virus infection results include previously published data obtained from three animals (27). Two animals of each group were sacrificed on day 7 postinfection, and three were sacrificed on day 12 postinfection, to assess dissemination and to harvest tissues for histological analysis.…”

Section: Cells and Transfectionsmentioning

confidence: 99%

“…For the biochemical analysis of recombinant proteins, 12-well plates of VerodogSLAMtag cells were transfected at ap-proximately 90% confluence as described previously (26,27). Briefly, each well was transfected with 2 g each of the H expression plasmid pCG-H5804Pzeo (34) or the respective mutant H plasmid and a plasmid expressing either the MeV Edmonston (3) or CDV 5804P F protein by use of Turbofect (Fermentas).…”

Section: Cells and Transfectionsmentioning

confidence: 99%

Canine Distemper Virus Epithelial Cell Infection Is Required for Clinical Disease but Not for Immunosuppression

Sawatsky

Wong

Hinkelmann

et al. 2012

J Virol

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To characterize the importance of infection of epithelial cells for morbillivirus pathogenesis, we took advantage of the severe disease caused by canine distemper virus (CDV) in ferrets. To obtain a CDV that was unable to enter epithelial cells but retained the ability to enter immune cells, we transferred to its attachment (H) protein two mutations shown to interfere with the interaction of measles virus H with its epithelial receptor, human nectin-4. As expected for an epithelial receptor (EpR)-blind CDV, this virus infected dog and ferret epithelial cells inefficiently and did not cause cell fusion or syncytium formation. On the other hand, the EpR-blind CDV replicated in cells expressing canine signaling lymphocyte activation molecule (SLAM), the morbillivirus immune cell receptor, with similar kinetics to those of wild-type CDV. While ferrets infected with wild-type CDV died within 12 days after infection, after developing severe rash and fever, animals infected with the EpR-blind virus showed no clinical signs of disease. Nevertheless, both viruses spread rapidly and efficiently in immune cells, causing similar levels of leukopenia and inhibition of lymphocyte proliferation activity, two indicators of morbillivirus immunosuppression. Infection was documented for airway epithelia of ferrets infected with wild-type CDV but not for those of animals infected with the EpR-blind virus, and only animals infected with wild-type CDV shed virus. Thus, epithelial cell infection is necessary for clinical disease and efficient virus shedding but not for immunosuppression.

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“…This implies a greater contribution of the henipavirus glycoproteins to the budding process, suggesting a fundamentally different process of henipavirus assembly compared with other members of this virus family. (Sawatsky & von Messling, 2010;Sawatsky et al, 2012). Briefly, each well was transfected with 2 mg of the parental CDV H or NiV G protein expression plasmid, or the respective mutants, using Turbofect (Thermo Fisher).…”

Section: Incorporation Of Niv G Into Vlps Is Non-specificmentioning

confidence: 99%

Morbillivirus and henipavirus attachment protein cytoplasmic domains differently affect protein expression, fusion support and particle assembly

Sawatsky

Bente

Czub

et al. 2016

Journal of General Virology

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The amino-terminal cytoplasmic domains of paramyxovirus attachment glycoproteins include trafficking signals that influence protein processing and cell surface expression. To characterize the role of the cytoplasmic domain in protein expression, fusion support and particle assembly in more detail, we constructed chimeric Nipah virus (NiV) glycoprotein (G) and canine distemper virus (CDV) haemagglutinin (H) proteins carrying the respective heterologous cytoplasmic domain, as well as a series of mutants with progressive deletions in this domain. CDV H retained fusion function and was normally expressed on the cell surface with a heterologous cytoplasmic domain, while the expression and fusion support of NiV G was dramatically decreased when its cytoplasmic domain was replaced with that of CDV H. The cell surface expression and fusion support functions of CDV H were relatively insensitive to cytoplasmic domain deletions, while short deletions in the corresponding region of NiV G dramatically decreased both. In addition, the first 10 residues of the CDV H cytoplasmic domain strongly influence its incorporation into virus-like particles formed by the CDV matrix (M) protein, while the co-expression of NiV M with NiV G had no significant effect on incorporation of G into particles. The cytoplasmic domains of both the CDV H and NiV G proteins thus contribute differently to the virus life cycle.

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Canine Distemper Viruses Expressing a Hemagglutinin without N-Glycans Lose Virulence but Retain Immunosuppression

Cited by 57 publications

References 56 publications

Identification of Key Residues in Virulent Canine Distemper Virus Hemagglutinin That Control CD150/SLAM-Binding Activity

Identification of Key Residues in Virulent Canine Distemper Virus Hemagglutinin That Control CD150/SLAM-Binding Activity

Canine Distemper Virus Epithelial Cell Infection Is Required for Clinical Disease but Not for Immunosuppression

Morbillivirus and henipavirus attachment protein cytoplasmic domains differently affect protein expression, fusion support and particle assembly

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