scholarly journals Sorting signals in the measles virus wild-type glycoproteins differently influence virus spread in polarized epithelia and lymphocytes

2009 ◽  
Vol 90 (10) ◽  
pp. 2474-2482 ◽  
Author(s):  
Nicole Runkler ◽  
Erik Dietzel ◽  
Mary Carsillo ◽  
Stefan Niewiesk ◽  
Andrea Maisner
Keyword(s):  
Epithelial Cells ◽  
Vaccine Strain ◽  
Measles Virus ◽  
Wild Type Virus ◽  
Type Virus ◽  
Virus Spread ◽  
Wild Type ◽  
Viral Spread ◽  
Sorting Signals ◽  
Polarized Epithelia

The spread of virus infection within an organism is partially dictated by the receptor usage of the virus and can be influenced by sorting signals present in the viral glycoproteins expressed in infected cells. In previous studies, we have shown that the haemagglutinin (H) and fusion protein (F) of the measles virus (MV) vaccine strain MVEdm harbour tyrosine-dependent sorting signals which influence virus spread in both lymphocytes and epithelial cells to a similar degree. In contrast with the vaccine strain, MV wild-type virus does not use CD46 but CD150/SLAM and a not clearly identified molecule on epithelial cells as receptors. To determine differences in viral spread between vaccine and wild-type virus, we generated recombinant MV expressing glycoproteins of both the wild-type strain WTFb and the corresponding tyrosine mutants. In contrast with observations based on vaccine virus glycoproteins, mutations in wild-type virus H and F differently influenced cell-to-cell fusion and replication in polarized epithelia and lymphocytes. For wild-type H, our data suggest a key role of the cytoplasmic tyrosine signal for virus dissemination in vivo. It seems to be important for efficient virus spread between lymphocytes, while the tyrosine signal in the F protein gains importance in epithelial cells as both signals have to be intact to allow efficient spread of infection within epithelia.

scholarly journals A double deletion prevents replication of the pestivirus bovine viral diarrhea virus in the placenta of pregnant heifers

2021 ◽  
Vol 17 (12) ◽  
pp. e1010107
Author(s):  
Jolene Carlson ◽  
Robert Kammerer ◽  
Jens Peter Teifke ◽  
Julia Sehl-Ewert ◽  
Christiane Pfarrer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Virus Replication ◽  
Post Infection ◽  
Deletion Mutant ◽  
Mutant Virus ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type ◽  
Double Deletion

In contrast to wild type bovine viral diarhea virus (BVDV) specific double deletion mutants are not able to establish persistent infection upon infection of a pregnant heifer. Our data shows that this finding results from a defect in transfer of the virus from the mother animal to the fetus. Pregnant heifers were inoculated with such a double deletion mutant or the parental wild type virus and slaughtered pairwise on days 6, 9, 10 and 13 post infection. Viral RNA was detected via qRT-PCR and RNAscope analyses in maternal tissues for both viruses from day 6 p.i. on. However, the double deletion mutant was not detected in placenta and was only found in samples from animals infected with the wild type virus. Similarly, high levels of wild type viral RNA were present in fetal tissues whereas the genome of the double deletion mutant was not detected supporting the hypothesis of a specific inhibition of mutant virus replication in the placenta. We compared the induction of gene expression upon infection of placenta derived cell lines with wild type and mutant virus via gene array analysis. Genes important for the innate immune response were strongly upregulated by the mutant virus compared to the wild type in caruncle epithelial cells that establish the cell layer on the maternal side at the maternal–fetal interface in the placenta. Also, trophoblasts which can be found on the fetal side of the interface showed significant induction of gene expression upon infection with the mutant virus although with lower complexity. Growth curves recorded in both cell lines revealed a general reduction of virus replication in caruncular epithelial cells compared to the trophoblasts. Compared to the wild type virus this effect was dramtic for the mutant virus that reached only a TCID50 of 1.0 at 72 hours post infection.

scholarly journals Vaccine-associated paralytic Poliomyelitis: a case report of domiciliary transmission

2000 ◽  
Vol 55 (3) ◽  
pp. 101-104 ◽  
Author(s):  
José A. Paz ◽  
Marcelo G. Vallada ◽  
Silvia N. C. H. Marques ◽  
Erasmo B. Casella ◽  
Heloisa H. S. Marques ◽  
...  
Keyword(s):  
Vaccine Strain ◽  
Wild Type Virus ◽  
Paralytic Poliomyelitis ◽  
Type Virus ◽  
Fecal Culture ◽  
Wild Type ◽  
Coding Region ◽  
Strain Vaccine ◽  
Unvaccinated Child ◽  
Type 3

Poliomyelitis associated with live strain vaccine is defined as the paralytic form of the acute anterior poliomyelitis related to the vaccine strain. Since these strains behave similarly to the wild-type virus, we can differentiate, epidemiologically, two types of vaccine-associated poliomyelitis: cases in which the patient was vaccinated and cases in which the patient had had contact with vaccinated individuals. We herein present the case of an unvaccinated child, with a clinical picture of an acute anterior poliomyelitis associated with the live strain vaccine, whose brother received the Sabin vaccine 20 days before the onset of the symptoms. Vaccine strain of the type 3 poliovirus was isolated in fecal culture and a presented mutation in nucleotide 472 (C<FONT FACE="Symbol">®</font>U) in the 5' non-coding region, which is strongly related to the higher strain virulence.

scholarly journals Attenuation of V- or C-Defective Measles Viruses: Infection Control by the Inflammatory and Interferon Responses of Rhesus Monkeys

2008 ◽  
Vol 82 (11) ◽  
pp. 5359-5367 ◽  
Author(s):  
Patricia Devaux ◽  
Gregory Hodge ◽  
Michael B. McChesney ◽  
Roberto Cattaneo
Keyword(s):  
Immune Responses ◽  
Measles Virus ◽  
Mononuclear Cells ◽  
Interferon Response ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type ◽  
Adaptive Immune Responses ◽  
C Protein ◽  
Adaptive Immune

ABSTRACT Patients recruited in virus-based cancer clinical trials and immunocompromised individuals in need of vaccination would profit from viral strains with defined attenuation mechanisms. We generated measles virus (MV) strains defective for the expression of either the V protein, a modulator of the innate immune response, or the C protein, which has multiple functions. The virulence of these strains was compared with that of the parental wild-type MV in a natural host, Macaca mulatta. Skin rash, viremia, and the strength of the innate and adaptive immune responses were characterized in groups of six animals. Replication of V- or C-protein-defective viruses was short-lived and reached lower levels in peripheral blood mononuclear cells and lymphatic organs compared to the wild-type virus; none of the mutants reverted to the wild type. The neutralizing antibody titers and MV-specific T-cell responses were equivalent in monkeys infected with the viral strains tested, documenting strong adaptive immune responses. In contrast, the inflammatory response was better controlled by wild-type MV, as revealed by inhibition of interleukin-6 and tumor necrosis factor alpha transcription. The interferon response was also better controlled by the wild-type virus than by the defective viruses. Since V- and C-defective MVs induce strong adaptive immune responses while spreading less efficiently, they may be developed as vaccines for immunocompromised individuals. Moreover, MV unable to interact with single innate immunity proteins may be developed for preferential replication in tumors with specific contexts of vulnerability.

scholarly journals Antigenic differences between wildtype measles viruses and vaccine viruses in Indonesia

2016 ◽  
Vol 48 (3) ◽  
pp. 125
Author(s):  
Made Setiawan ◽  
Agus Sjahrurachman ◽  
Fera Ibrahim ◽  
Agus Suwandono
Keyword(s):  
Measles Virus ◽  
Neutralization Test ◽  
Vaccine Virus ◽  
Structural Proteins ◽  
Wild Type Virus ◽  
Type Virus ◽  
Measles Vaccine ◽  
Wild Type ◽  
Examination Technique ◽  
Cross Neutralization

Background Measles virus has a single, negative strand RNAgenome which codes 6 structural proteins: N, F, P M, H and L.Currently there are several variances in the nucleotide sequencesof N, F, M and H genes across wild type measles viruses, hencemeasles viruses can be categorized into clades and genotypes. Theantigenicity of the previous genotype of measles is different fromthe current genotype.Objective To determine the antigenic differences between wildtype measles virus and measles vaccine virus.Methods Analysis of the antigenic differences between wild typevirus (G2, G3 and D9) and vaccine virus (CAM-70 and Schwarz)was performed by immunizing mice with the respective viruses.The serum was then tested with micro-cross-neutralizationtechnique using the G2, G3, D9 and CAM-70 virus. Tests withcross ELISA examination technique were also performed usingthe same set of virus.Results Analysis of the cross neutralization test and cross ELISAshowed that the highest antigenicity reaction was found betweenwild type virus with antibody against wild type virus, while thelowest reaction was between wild type virus with antibody againstCAM-70.Conclusions We conclude that the antigenicity of antigenic proteinfrom wild type virus is higher than antigenicity of vaccine virusprotein. In addition, it was found that the antigenicity of proteinsfrom Schwarz vaccine virus was higher than proteins CAM-70vaccine virus.

scholarly journals Differences of antigenic profiles on immunoblotting of wild type measles virus and vaccine virus in Indonesia

2016 ◽  
Vol 48 (6) ◽  
pp. 364
Author(s):  
Made Setiawan ◽  
Agus Sjahrurachman ◽  
Fera Lbrahim ◽  
Agus Suwandono
Keyword(s):  
Measles Virus ◽  
Vaccine Virus ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type ◽  
Mmr Vaccine ◽  
N Protein ◽  
Antibody Titers ◽  
Antigen Antibody ◽  
Very High

Background Measles virus has a negative, single strand RNAgenome which codes for six important structural proteins. Thegenes of the wild type measles virus have many variances hencethe nucleotide sequences of each wild type virus and vaccine virusare different. This differences lead to the antigenic differencesbetween wild type and vaccine virus.Objective The purpose of this research is to investigate thedifferences in the antigenic profiles on immunoblotting betweenwild type and vaccine virus.Results The analysis results are 1) the antigen ofCAM-70 vaccinevirus was less able in cross reacting with the antibodies from G2,G3, 09, CAM-70 and Schwarz; 2) The antibody aga inst CAM-70 was only able to cross react with antigens of N protein and afew of antigens ofF proteins; 3) The wild type virus were veryimmunogenic, hence the antibody titers were very high; 4) TheCAM-70 and MMR vaccine virus were less immunogenic, hencetheir antibody were very low; 5) The antibody responses thatalways occurred from all immunized mice serum were antibodyfor N and F proteins. However, the antibody against CAM-70vaccine virus was still able to react with wild type virus (G2, G3and 09).Conclusion All antigen-antibody reaction on immunoblottingresulted in different profiles especially between wild type virusand CAM-70 vaccine virus. Although CAM-70 vaccine virusshowed clear differences compared to G2, G3 and 09 genotypes,antibodies against CAM-70 were still able to cross react withantigens from other genotypes (G2, G3 and D9).

scholarly journals Difference of hemaglutinins between wild-type and vaccine measles virus in Indonesia

2008 ◽  
Vol 48 (1) ◽  
pp. 42
Author(s):  
Made Setiawan ◽  
Agus Sjahrurachman ◽  
Fera Ibrahim ◽  
Agus Suwandono
Keyword(s):  
Neutralizing Antibodies ◽  
Measles Virus ◽  
Vaccine Virus ◽  
Amino Acid Sequences ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type ◽  
Cell Infection ◽  
Aminoacid Sequence ◽  
H Protein

Background Hemaglutinin (H) protein of measles virus is veryimportant in the process of host cell infection. H protein is alsoable to induce specific antibodies which can neutralize measlesvirus and block the cell infection.Objective This study aimed to explore the nucleotide and aminoacid sequence differences between wild-type measles virus (G2,G3 and D9) with CAM-70, Schwarz and Edmonston-wt vaccinevirus.Methods The exctration and amplification of the gene wereconducted in the laboratory using biomolecular technology. Thegene and protein analysis were conducted using the bioinformatictechnology.Results The results showed that the differences in nucleotidesequences were highest between wild-type virus and CAM-70vaccine virus (76-77 nucleotides), followed by Schwarz (61-64nucleotides) and Edmonston (60-63 nucleotides). The differencesin amino acid sequences were highest between wild-type virusand CAM-70 (24-29 residues), followed by Schwarz (13-20residues) and Edmonston (12-19 residues).Conclusion The Indonesian wild-type measles virus was geneticallycloser to Schwarz vaccine virus than CAM-70 vaccine virus,hence the neutralizing antibodies generated by Schwarz vaccinewere more specific against Indonesian wild-type virus comparedto CAM-70 vaccine.

scholarly journals Infection of hepatocytes with 17-D vaccine-strain yellow fever virus induces a strong pro-inflammatory host response

2011 ◽  
Vol 92 (10) ◽  
pp. 2262-2271 ◽  
Author(s):  
Sara E. Woodson ◽  
Michael R. Holbrook
Keyword(s):  
Yellow Fever ◽  
Vaccine Strain ◽  
Host Response ◽  
Yellow Fever Virus ◽  
Vaccine Virus ◽  
Fever Virus ◽  
Productive Infection ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type

Yellow fever virus (YFV) causes serious disease in endemic areas of South America and Africa, even though a very well tolerated vaccine is available. YFV primarily targets the liver where as many as 80 % of hepatocytes may be involved during infection. The objective of this project was to compare and contrast the cytokine response from hepatocytes infected with either wild-type (Asibi) or vaccine (17-D-204) strains of YFV, with the goal of identifying responses that might be correlated with disease severity or vaccine efficacy. We report here that PH5CH8 hepatocytes support a productive infection with both wild-type and vaccine-strain YFV. Infection with either virus resulted in elevated expression of several pro- and anti-inflammatory cytokines [interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-10 and tumour necrosis factor-α) with a corresponding increase in transcription. Hepatocytes infected with vaccine virus had a more profound response than did cells infected with wild-type virus. Pre-stimulation of hepatocytes with IL-6 resulted in reduced viral titres, elevated concentrations of cytokines released from Asibi virus-infected cells and improved cell viability in cells infected with 17-D virus. Data reported here suggest that 17-D virus stimulates an appropriate antiviral inflammatory response in hepatocytes, while Asibi virus can attenuate the host response. These data identify potential mechanisms that are associated with increased virulence in wild-type virus infections and also provide clues towards potential immune-response limitations that may be associated with vaccine-related adverse events.

scholarly journals The R33 G Protein-Coupled Receptor Gene of Rat Cytomegalovirus Plays an Essential Role in the Pathogenesis of Viral Infection

1998 ◽  
Vol 72 (3) ◽  
pp. 2352-2363 ◽  
Author(s):  
Patrick S. Beisser ◽  
Cornelis Vink ◽  
Joanne G. Van Dam ◽  
Gert Grauls ◽  
Sabina J. V. Vanherle ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Epithelial Cells ◽  
Salivary Glands ◽  
G Protein ◽  
Mutant Strain ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type ◽  
Salivary Gland Epithelial Cells ◽  
G Protein Coupled

ABSTRACT We have identified a rat cytomegalovirus (RCMV) gene that encodes a G-protein-coupled receptor (GCR) homolog. This gene (R33) belongs to a family that includes the human cytomegalovirus UL33 gene. R33 was found to be transcribed during the late phase of RCMV infection in rat embryo fibroblasts. Unlike the mRNAs from all the other members of the UL33 family that have been studied to date, the R33 mRNA is not spliced. To study the function of the R33 gene, we constructed an RCMV strain in which the R33 open reading frame is disrupted. The mutant strain (RCMVΔR33) did not show differences in replication from wild-type RCMV upon infection of several rat cell types in vitro. However, marked differences were seen between the mutant and wild-type strain in the pathogenesis of infection in immunocompromised rats. First, the mutant strain induced a significantly lower mortality than the wild-type virus did. Second, in contrast to wild-type RCMV, the mutant strain did not efficiently replicate in the salivary gland epithelial cells of immunocompromised rats. Although viral DNA was detected in salivary glands of RCMVΔR33-infected rats up to 14 days postinfection, it could not be detected at later time points. This indicates that although the strain with R33 deleted is probably transported to the salivary glands in a similar fashion to that for wild-type virus, the mutant virus is not able to either enter or replicate in salivary gland epithelial cells. We conclude that the RCMV R33 gene plays a vital role in the pathogenesis of infection.

scholarly journals Extent of Measles Virus Spread and Immune Suppression Differentiates between Wild-Type and Vaccine Strains in the Cotton Rat Model (Sigmodon hispidus)

2003 ◽  
Vol 77 (1) ◽  
pp. 150-158 ◽  
Author(s):  
Joanna Pfeuffer ◽  
Karen Püschel ◽  
Volker ter Meulen ◽  
Jürgen Schneider-Schaulies ◽  
Stefan Niewiesk
Keyword(s):  
Rat Model ◽  
Immune Suppression ◽  
Measles Virus ◽  
Ex Vivo ◽  
Vaccine Virus ◽  
Wild Type Virus ◽  
Wild Type ◽  
Spleen Cells ◽  
Cotton Rat ◽  
Viral Spread

ABSTRACT Infection of humans with wild-type measles virus leads to strong immune suppression and secondary infections, whereas immunization with an attenuated vaccine strain does not. Using the cotton rat model (Sigmodon hispidus), we investigated whether vaccine and wild-type viruses differ in viral spread and whether this is correlated with inhibition of of proliferation of spleen cells ex vivo after mitogen stimulation. After intranasal infection of cotton rats with wild-type and vaccine strains, it was found that wild-type virus replicates better in lung tissue, spreads to the mediastinal lymph nodes, and induces a more pronounced and longer-lasting inhibition of proliferation of spleen cells ex vivo after mitogen stimulation than does vaccine virus. To induce the same degree of proliferation inhibition, 1,000-fold less wild-type virus was required than vaccine virus. With this system, the virulence of various measles virus isolates and recombinant viruses was tested. Four (in humans and/or monkeys) highly pathogenic virus strains were immunosuppressive, whereas viruses of vaccine virus genotype A were not. Using virus pairs which, due to passage on fibroblasts versus lymphoid cells or due to a point mutation in the hemagglutinin (N481 → Y), differed in their usage of the two receptor molecules CD46 and CD150 on human cells, it was found that viruses using exclusively CD150 in vitro spread to mediastinal lymph nodes and induced strong immune suppression. These data demonstrate that important parameters of virulence seen in humans, such as viral spread and immune suppression, are reflected in the cotton rat model.

scholarly journals A study of primary neuronal infection by mutants of herpes simplex virus type 1 lacking dispensable and non-dispensable glycoproteins

1999 ◽  
Vol 80 (9) ◽  
pp. 2403-2409 ◽  
Author(s):  
N. Babic ◽  
G. Rodger ◽  
J. Arthur ◽  
A. C. Minson
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Epithelial Cells ◽  
Dorsal Root ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type ◽  
Glycoprotein C ◽  
Simplex Virus

Cultures of primary rat dorsal root ganglia neurones were inoculated with various doses of herpes simplex virus mutants deficient in glycoproteins B, D, H, C, G, E, I or J, and the proportion of infected neurones was determined. The behaviour of these mutants on primary neurones was broadly similar to their behaviour on fibroblasts or epithelial cells. Thus, virions lacking the ‘non-dispensable’ glycoproteins B, D or H were incapable of infecting primary neurones, whereas mutants lacking glycoproteins G, E, I or J infected primary neurones with the same efficiency as wild-type virions. Two independently derived mutants lacking gC displayed a marginal phenotype, infecting neurones with a five- to tenfold reduced efficiency relative to wild-type virus and relative to non-neuronal cells in the same cultures. We conclude that the virion glycoprotein requirements for infection of mammalian neurones are similar to those required for infection of fibroblasts and epithelial cells but that glycoprotein C may enhance infection of neurones.

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