Yellow fever virus strains Asibi and 17D-204 infect human umbilical cord endothelial cells and induce novel changes in gene expression

In order to investigate the pathogenicity of the virus strain GOI 4191 that was isolated from a fatal adverse event after yellow fever virus (YFV) vaccination, an experimental assay using hamsters (Mesocricetus auratus) as animal model and YFV 17DD vaccine strain as virus reference was accomplished. The two virus strains were inoculated by intracerebral, intrahepatic and subcutaneous routes. The levels of viremia, antibody response, and aminotransferases were determined in sera; while virus, antigen and histopathological changes were determined in the viscera. No viremia was detected for either strain following infection; the immune response was demonstrated to be more effective to strain GOI 4191; and no significant aminotransferase levels alterations were detected. Strain GOI 4191 was recovered only from the brain of animals inoculated by the IC route. Viral antigens were detected in liver and brain by immunohistochemical assay. Histothological changes in the viscera were characterized by inflammatory infiltrate, hepatocellular necrosis, and viral encephalitis. Histological alterations and detection of viral antigen were observed in the liver of animals inoculated by the intrahepatic route. These findings were similar for both strains used in the experiment; however, significant differences were observed from those results previously reported for wild type YFV strains.

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Modulation of gene expression by hypoxia in human umbilical cord vein endothelial cells: A transcriptomic and proteomic study (vol. 4, Issue 6, pp. 1737-1760)

PROTEOMICS ◽

10.1002/pmic.200490057 ◽

2004 ◽

Vol 4 (9) ◽

pp. 2822-2822

Author(s):

Simone B. Scheurer ◽

Jascha N. Raybak ◽

Christoph Rösli ◽

Dario Neri ◽

Giuliano Elia

Keyword(s):

Gene Expression ◽

Endothelial Cells ◽

Umbilical Cord ◽

Human Umbilical Cord ◽

Proteomic Study ◽

Modulation Of Gene Expression ◽

Umbilical Cord Vein ◽

Human Umbilical Cord Vein

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Genomic and Phylogenetic Characterization of Brazilian Yellow Fever Virus Strains

Journal of Virology ◽

10.1128/jvi.00565-12 ◽

2012 ◽

Vol 86 (24) ◽

pp. 13263-13271 ◽

Cited By ~ 26

Author(s):

M. R. T. Nunes ◽

G. Palacios ◽

J. F. Cardoso ◽

L. C. Martins ◽

E. C. Sousa ◽

...

Keyword(s):

Yellow Fever ◽

Yellow Fever Virus ◽

Fever Virus ◽

Phylogenetic Characterization ◽

Virus Strains

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Genetic Heterogeneity of Yellow Fever Virus Strains from Africa and the Americas

Journal of General Virology ◽

10.1099/0022-1317-67-1-209 ◽

1986 ◽

Vol 67 (1) ◽

pp. 209-213 ◽

Cited By ~ 30

Author(s):

V. Deubel ◽

J.-P. Digoutte ◽

T. P. Monath ◽

M. Girard

Keyword(s):

Yellow Fever ◽

Genetic Heterogeneity ◽

Yellow Fever Virus ◽

Fever Virus ◽

Virus Strains

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A Sensitive Yellow Fever Virus Entry Reporter Identifies Valosin-Containing Protein (VCP/p97) as an Essential Host Factor for Flavivirus Uncoating

Proceedings ◽

10.3390/proceedings2020050147 ◽

2020 ◽

Vol 50 (1) ◽

pp. 147

Author(s):

Shuo Zhang ◽

Harish N. Ramanathan ◽

Florian Douam ◽

Katrina B. Mar ◽

Jinhong Chang ◽

...

Keyword(s):

Gene Expression ◽

Yellow Fever ◽

Yellow Fever Virus ◽

Virus Entry ◽

Critical Role ◽

Viral Gene Expression ◽

Rna Replication ◽

Fever Virus ◽

Viral Gene ◽

Positive Strand Rna

Flaviviruses are enveloped, arthropod-borne, positive-strand RNA viruses that cause significant human disease. While the basic mechanisms of flavivirus entry and fusion are understood, little is known about the postfusion events that precede RNA replication, such as nucleocapsid disassembly. We recently developed a sensitive, conditionally replication-defective yellow fever virus (YFV) entry reporter to quantitively monitor the translation of incoming virus particle-delivered genomes. We validated that viral gene expression can be neutralized by YFV-specific antisera and requires known pathways of flavivirus entry; however, as expected, gene expression from the defective reporter virus was insensitive to a small molecule inhibitor of YFV RNA replication. The initial round of viral gene expression was also shown to require: (i) cellular ubiquitylation, consistent with recent findings that dengue virus capsid protein must be ubiquitylated in order for nucleocapsid uncoating to occur, and (ii) valosin-containing protein (VCP)/p97, a cellular ATPase that unfolds and extracts ubiquitylated client proteins from large macromolecular complexes. RNA transfection and washout experiments showed that VCP/p97 functions at a postfusion, pretranslation step in YFV entry. Together, these data support a critical role for VCP/p97 in the disassembly of incoming flavivirus nucleocapsids during a postfusion step in virus entry.

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A histone-like motif in yellow fever virus contributes to viral replication

10.1101/2020.05.05.078782 ◽

2020 ◽

Author(s):

Diego Mourão ◽

Shoudeng Chen ◽

Uwe Schaefer ◽

Leonia Bozzacco ◽

Leticia A. Carneiro ◽

...

Keyword(s):

Gene Expression ◽

Yellow Fever ◽

Yellow Fever Virus ◽

Rna Virus ◽

Fever Virus ◽

Host Protein ◽

Histone H4 ◽

Host Proteins ◽

Control Of Gene Expression ◽

Lysine Residues

The mimicry of host proteins by viruses contributes to their ability to suppress antiviral immunity and hijack host biosynthetic machinery1. Host adaptation to evade this exploitation depends on host protein functional redundancy2. Non-redundant, essential host proteins have limited potential to adapt without severe consequences3. Histones, which are essential for genome architecture and control of gene expression, are among the most evolutionary conserved proteins4. Here we show that the capsid protein of the flavivirus yellow fever virus (YFV), mimics histone H4 and interferes with chromatin gene regulation by BRD4, a bromodomain and extraterminal domain (BET) protein. Two acetyl-lysine residues of YFV capsid are embedded in a histone-like motif that interacts with the BRD4 bromodomain, affecting gene expression and influencing YFV replication. These findings reveal histone mimicry as a strategy employed by an RNA virus that replicates in the cytosol5 and define convergent and distinct molecular determinants for motif recognition of the viral mimic versus histone H4.

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Isolations in a Mosquito (Aedes pseudoscutellaris) Cell Line (Mos. 61) of Yellow Fever Virus Strains from Original Field Material

Intervirology ◽

10.1159/000149453 ◽

1975 ◽

Vol 6 (1) ◽

pp. 50-56 ◽

Cited By ~ 20

Author(s):

Raja Varma ◽

Mary Pudney ◽

Colin J. Leake ◽

Pauline H. Peralta

Keyword(s):

Cell Line ◽

Yellow Fever ◽

Yellow Fever Virus ◽

Fever Virus ◽

Original Field ◽

Virus Strains

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NON-FATAL INFECTION OF MICE FOLLOWING INTRACEREBRAL INOCULATION OF YELLOW FEVER VIRUS

Journal of Experimental Medicine ◽

10.1084/jem.77.6.507 ◽

1943 ◽

Vol 77 (6) ◽

pp. 507-520 ◽

Cited By ~ 5

Author(s):

John P. Fox

Keyword(s):

Yellow Fever ◽

Yellow Fever Virus ◽

Complete Recovery ◽

Fever Virus ◽

Intracerebral Inoculation ◽

Virus Dose ◽

Small Doses ◽

Protective Antibodies ◽

High Degree ◽

Virus Strains

Observations have been reported which indicate that mice inoculated intracerebrally with active yellow fever virus may develop an infection which is not only non-fatal but may also be completely inapparent. The most extensive observations were made on mice which showed signs of infection but were still alive 22 days after inoculation with virus of one or another of several 17D substrains. In such cases, the infection usually progressed no further and partial or complete recovery often ensued. Agents other than yellow fever virus were excluded as a significant cause of such nonfatal infections by the failure of repeated attempts to isolate other infective agents, by the demonstration of antibodies against yellow fever virus in the sera of the mice, and by the demonstration of a high degree of resistance on the part of such surviving mice to reinoculation with large doses of neurotropic yellow fever virus. Completely inapparent infections with 17D virus were also shown to occur. Studies of apparently normal survivors of 17D virus titrations revealed a small but significant number of animals resistant to intracerebral challenge with neurotropic yellow fever virus. Further, pooled sera from such mice were shown to contain specific protective antibodies. The occurrence of non-fatal infections with 17D virus was found related to virus dose and substrain. Small doses of virus provoked a significantly higher proportion of non-fatal infections than large doses; while different 17D substrains, tested over equivalent ranges of virus dose, varied greatly with respect to the proportion of infections which did not terminate with death. In the case of two substrains (17DD low and 17D3), non-fatal infections (as demonstrated by resistance to intracerebral challenge with neurotropic virus) were sufficiently frequent to cause an increase, when included in the computation of the infective titers, of 25 per cent above the figures based on deaths alone. The demonstration of non-fatal infections, thus, may be important to the accuracy of quantitative determinations of infectivity. Limited observations with virus of the French neurotropic and the pantropic Asibi strains revealed that non-fatal infections do occur, but only rarely. Somewhat more extensive observations with unmodified virus of strains isolated from Brazilian cases of jungle yellow fever, in contrast, revealed an occurrence of non-fatal infections much greater than that observed with the most productive 17D substrains. With these jungle strains, the demonstration of non-fatal infections proved indispensable to any measure of the level of infectivity of virus preparations. The demonstration of the proportional occurrence in mice of non-fatal infections with yellow fever virus provides an additional means by which different virus strains and substrains may be characterized.

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A Sensitive Yellow Fever Virus Entry Reporter Identifies Valosin-Containing Protein (VCP/p97) as an Essential Host Factor for Flavivirus Uncoating

10.1101/814764 ◽

2019 ◽

Author(s):

Harish N. Ramanathan ◽

Shuo Zhang ◽

Florian Douam ◽

Jinhong Chang ◽

Priscilla L. Yang ◽

...

Keyword(s):

Gene Expression ◽

Yellow Fever ◽

Yellow Fever Virus ◽

Virus Entry ◽

Critical Role ◽

Rna Replication ◽

Cellular Protein ◽

Fever Virus ◽

Rna Transfection ◽

Endosomal Acidification

ABSTRACTWhile the basic mechanisms of flavivirus entry and fusion are understood, little is known about the post-fusion events that precede RNA replication, such as nucleocapsid disassembly. We describe here a sensitive, conditionally replication-defective yellow fever virus (YFV) entry reporter, YFVΔSK/Nluc, to quantitively monitor the translation of incoming, virus particle-delivered genomes. We validated that YFVΔSK/Nluc gene expression can be neutralized by YFV-specific antisera and requires known flavivirus entry pathways, including clathrin- and dynamin-mediated endocytosis, endosomal acidification, YFV E glycoprotein-mediated fusion, and cellular LY6E expression; however, as expected, gene expression from the defective reporter virus was insensitive to a small molecule inhibitor of YFV RNA replication. YFVΔSK/Nluc gene expression was also shown to require cellular ubiquitylation, consistent with recent findings that dengue virus capsid protein must be ubiquitylated in order for nucleocapsid uncoating to occur, as well as valosin-containing protein (VCP)/p97, a cellular ATPase that unfolds and extracts ubiquitylated client proteins from large macromolecular complexes. RNA transfection and washout experiments showed that VCP/p97 functions at a post-fusion, pre-translation step in YFV entry. Together, these data support a critical role for VCP/p97 in the disassembly of incoming flavivirus nucleocapsids during a post-fusion step in virus entry.IMPORTANCEFlaviviruses are an important group of RNA viruses that cause significant human disease. The mechanisms by which flavivirus nucleocapsids are disassembled during virus entry remain unclear. Here we show that the yellow fever virus nucleocapsid disassembly requires the cellular protein-disaggregating enzyme valosin-containing protein, also known as p97.

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