Measles virus: both the haemagglutinin and fusion glycoproteins are required for fusion

Wild, T. F.; Malvoisin, Etienne; Buckland, Robin

doi:10.1099/0022-1317-72-2-439

Cited by 214 publications

(140 citation statements)

References 16 publications

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“…Viruses like measles virus carry on their surface glycoproteins that promote cell-to-cell fusion (2,45); cell-to-cell fusion of infected cells can be seen as an effective increase of the MOI. On the other hand, many viruses, including VSV, have mechanisms leading to superinfection exclusion (44), limiting the number of virions that coinfect the same cell.…”

Section: Discussionmentioning

confidence: 99%

Density-Dependent Selection in Vesicular Stomatitis Virus

Novella

Reissig

Wilke

2004

J Virol

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We used vesicular stomatitis virus to test the effect of complementation on the relative fitness of a deleterious mutant, monoclonal antibody-resistant mutant (MARM) N, in competition with its wild-type ancestor. We carried out competitions of MARM N and wild-type populations at different multiplicities of infection (MOIs) and initial ratios of the wild type to the mutant and found that the fitness of MARM N relative to that of the wild type is very sensitive to changes in the MOI (i.e., the degree of complementation) but depends little, if at all, on the initial frequencies of MARM N and the wild type. Further, we developed a mathematical model under the assumption that during coinfection both viruses contribute to a common pool of protein products in the infected cell and that they both exploit this common pool equally. Under such conditions, the fitness of all virions that coinfect a cell is the average fitness in the absence of coinfection of that group of virions. In the absence of coinfection, complementation cannot take place and the relative fitness of each competitor is only determined by the selective value of its own products. We found good agreement between our experimental results and the model predictions, which suggests that the wild type and MARM N freely share all of their gene products under coinfection.RNA viruses form highly polymorphic populations called quasispecies (8,9,13). The origin of much of their genetic diversity is high mutational pressure. Most RNA viruses have mutation rates on the order of one miscopied base per genome and generation (10, 11). However, high mutational pressure is not necessarily the only factor promoting genetic diversity. Niche differentiation can allow stable polymorphisms in an infected host. For instance, during a polyclonal immune response, different subpopulations may have different sensitivities to individual antibodies; variation within a host can also be related to differences in the tropism of different viral subpopulations. Virus-virus interactions may also promote stable polymorphisms in an infected host. In cell culture, such interactions readily occur during replication inside a cell and are likely to be an important contributor to the maintenance of variation. When two or more virions coinfect the same cell, complementation can take place. Not every function can be complemented in trans. In positive-stranded viruses, translation and replication are coupled (25); therefore, many functions need to be provided in cis and cannot be rescued by complementation (33, 37). Other proteins can freely interact with heterologous genomes or replicons, even from different viral species (18,21). In the absence of compartmentalization or other limitations to the diffusion of viral products, soluble proteins can interact with any genome inside the cell, potentially changing the phenotype of the virions and masking targets for natural selection to operate. A remarkable example of this phenomenon is phenotypic mixing and hiding, particularly for monoclonal antibody (...

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Section: Discussionmentioning

confidence: 99%

Density-Dependent Selection in Vesicular Stomatitis Virus

Novella

Reissig

Wilke

2004

J Virol

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“…Alternatively, it has been shown that the coexpression of the HA and F proteins was necessary for cell fusion [5,13,20,26,27,29]. Consequently, several models have been suggested that the HA protein was significant in triggering cell fusion [18,27].…”

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confidence: 99%

The Nucleotide and Predicted Amino Acid Sequence of the Fusion Protein of Recent Isolates of Canine Distemper Virus in Japan.

Iwatsuki

Miyashita

Yoshida

et al. 1998

The Journal of Veterinary Medical Science

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ABSTRACT. Analysis of the molecular properties of fusion (F) proteins of field isolates of canine distemper virus (CDV) by immunoprecipitation analysis revealed an identical molecular mass of F protein of 3 field isolates as well as the Onderstepoort laboratory strain. Sequencing showed that the F gene of a field isolate (the Yanaka strain) shared 90.1% and 95.7% identities with the Onderstepoort strain at nucleotide and amino acid levels, respectively. All of the 13 cysteine residues and 4 potential asparagine-linked glycosylation sites were completely conserved amongst these strains. These results indicate that the F proteins is much less heterogeneous than that observed in the hemagglutinin proteins of CDV.-KEY WORDS: CDV, field isolate, fusion protein.

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“…1 Antitumor activity of attenuated strains of measles virus derived from the Edmonston vaccine lineage has been demonstrated in models of lymphoma, 2 multiple myeloma, 3 ovarian cancer, 4 hepatocellular carcinoma, 5 glioblastoma multiforme 6 and breast cancer. 7 After infection of tumor cells, the virus causes a very characteristic cytopathic effect, the development of multinucleated giant cells (syncytia).…”

Section: Introductionmentioning

confidence: 99%

Heat shock protein inhibitors increase the efficacy of measles virotherapy

Liu

Erlichman

et al. 2008

Gene Ther

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Oncolytic measles virus strains have activity against multiple tumor types and are currently in phase I clinical testing. Induction of the heat shock protein 70 (HSP70) constitutes one of the earliest changes in cellular gene expression following infection with RNA viruses including measles virus, and HSP70 upregulation induced by heat shock has been shown to result in increased measles virus cytotoxicity. HSP90 inhibitors such as geldanamycin (GA) or 17-allylaminogeldanamycin result in pharmacologic upregulation of HSP70 and they are currently in clinical testing as cancer therapeutics. We therefore investigated the hypothesis that heat shock protein inhibitors could augment the measles virus-induced cytopathic effect. We tested the combination of a measles virus derivative expressing soluble human carcinoembryonic antigen (MV-CEA) and GA in MDA-MB-231 (breast), SKOV3.IP (ovarian) and TE671 (rhabdomyosarcoma) cancer cell lines. Optimal synergy was accomplished when GA treatment was initiated 6-24 h following MV infection. Western immunoblotting confirmed HSP70 upregulation in combination-treated cells. Combination treatment resulted in statistically significant increase in syncytia formation as compared to MV-CEA infection alone. Clonogenic assays demonstrated significant decrease in tumor colony formation in MV-CEA/GA combination-treated cells. In addition there was increase in apoptosis by 4,6-diamidino-2-phenylindole staining. Western immunoblotting for caspase-9, caspase-8, caspase-3 and poly(ADP-ribose) polymerase (PARP) demonstrated increase in cleaved caspase-8 and PARP. The pan-caspase inhibitor Z-VAD-FMK and caspase-8 inhibitor Z-IETD-FMK, but not the caspase-9 inhibitor Z-IEHD-FMK, protected tumor cells from MV-CEA/GA-induced PARP activation, indicating that apoptosis in combinationtreated cells occurs mainly via the extrinsic caspase pathway. Treatment of normal cells, such as normal human fibroblasts, however, with the MV-CEA/GA combination, did not result in cytopathic effect, indicating that GA did not alter the MV-CEA specificity for tumor cells. One-step viral growth curves, western immunoblotting for MV-N protein expression, QRT-PCR quantitation of MV-genome copy number and CEA levels showed comparable proliferation of MV-CEA in GAtreated vs -untreated tumor cells. Rho activation assays and western blot for total RhoA, a GTPase associated with the actin cytoskeleton, demonstrated decrease in RhoA activation in combination-treated cells, a change previously shown to be associated with increase in paramyxovirus-induced cell-cell fusion. The enhanced cytopathic effect resulting from measles virus/GA combination supports the translational potential of this approach in the treatment of cancer.

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Measles virus: both the haemagglutinin and fusion glycoproteins are required for fusion

Cited by 214 publications

References 16 publications

Density-Dependent Selection in Vesicular Stomatitis Virus

Density-Dependent Selection in Vesicular Stomatitis Virus

The Nucleotide and Predicted Amino Acid Sequence of the Fusion Protein of Recent Isolates of Canine Distemper Virus in Japan.

Heat shock protein inhibitors increase the efficacy of measles virotherapy

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