scholarly journals Yellow Fever Virus Down-Regulates mRNA Expression of SOCS1 in the Initial Phase of Infection in Human Cell Lines

Viruses ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 802
Author(s):  
Michael B. Yakass ◽  
David Franco ◽  
Osbourne Quaye
Keyword(s):  
Mrna Expression ◽  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Expression Patterns ◽  
Fever Virus ◽  
Effective Vaccine ◽  
Interferon Β ◽  
Infected Cells ◽  
Insight Into

Flaviviruses are constantly evolving diverse immune evasion strategies, and the exploitation of the functions of suppressors of cytokine signalling (SOCS) and protein inhibitors of activated STATs (PIAS) to favour virus replication has been described for Dengue and Japanese encephalitis viruses but not for yellow fever virus (YFV), which is still of global importance despite the existence of an effective vaccine. Some mechanisms that YFV employs to evade host immune defence has been reported, but the expression patterns of SOCS and PIAS in infected cells is yet to be determined. Here, we show that SOCS1 is down-regulated early in YFV-infected HeLa and HEK 293T cells, while SOCS3 and SOCS5 are not significantly altered, and PIAS mRNA expression appears to follow a rise-dip pattern akin to circadian-controlled genes. We also demonstrate that YFV evades interferon-β application to produce comparable viral titres. This report provides initial insight into the in vitro expression dynamics of SOCS and PIAS upon YFV infection and a basis for further investigation into SOCS/PIAS expression and how these modulate the immune response in animal models.

scholarly journals AT-752, a double prodrug of a guanosine nucleotide analog, inhibits yellow fever virus in a hamster model

2021 ◽  
Author(s):  
Kai Lin ◽  
Steven S Good ◽  
Justin G. Julander ◽  
Abbie Weight ◽  
Adel Moussa
Keyword(s):  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Limit Of Detection ◽  
Virus Titer ◽  
Fever Virus ◽  
Effective Vaccine ◽  
Hamster Model ◽  
Nucleotide Analog

Yellow fever virus (YFV) is a zoonotic pathogen re-emerging in parts of the world, causing a viral hemorrhagic fever associated with high mortality rates. While an effective vaccine is available, having an effective antiviral against YFV is critical against unexpected outbreaks, or when vaccination is not recommended. We have previously identified AT-281, the free base of AT-752, an orally available double prodrug of a guanosine nucleotide analog, as a potent inhibitor of YFV in vitro , with a 50% effective concentration (EC 50 ) of 0.31 µM. In hamsters infected with YFV (Jimenez strain), viremia rose about 4 log 10 -fold and serum alanine aminotransferase (ALT) 2-fold compared to sham-infected animals. Treatment with 1000 mg/kg AT-752 for 7 days, initiated 4 h prior to viral challenge, reduced viremia to below the limit of detection by day 4 post infection (pi) and returned ALT to normal levels by day 6 pi. When treatment with AT-752 was initiated 2 days pi, the virus titer and ALT dropped >2 log 10 and 53% by day 4 and 6 pi, respectively. In addition, at 21 days pi, 70 – 100% of the infected animals in the treatment groups survived compared to 0% of the untreated group (p<0.001). Moreover, in vivo formation of the active triphosphate metabolite AT-9010 was measured in the animal tissues, with the highest concentrations in liver and kidney, organs that are vulnerable to the virus. The demonstrated in vivo activity of AT-752 suggests that it is a promising compound for clinical development in the treatment of YFV infection.

scholarly journals Yellow Fever Outbreak in Eastern Senegal, 2020–2021

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1475
Author(s):  
Moussa Moïse Diagne ◽  
Marie Henriette Dior Ndione ◽  
Alioune Gaye ◽  
Mamadou Aliou Barry ◽  
Diawo Diallo ◽  
...  
Keyword(s):  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Mosquito Species ◽  
Virus Transmission ◽  
Genomic Analysis ◽  
Hemorrhagic Fever ◽  
Fever Virus ◽  
World Health ◽  
Effective Vaccine ◽  
Ministry Of Health

Yellow fever virus remains a major threat in low resource countries in South America and Africa despite the existence of an effective vaccine. In Senegal and particularly in the eastern part of the country, periodic sylvatic circulation has been demonstrated with varying degrees of impact on populations in perpetual renewal. We report an outbreak that occurred from October 2020 to February 2021 in eastern Senegal, notified and managed through the synergistic effort yellow fever national surveillance implemented by the Senegalese Ministry of Health in collaboration with the World Health Organization, the countrywide 4S network set up by the Ministry of Health, the Institut Pasteur de Dakar, and the surveillance of arboviruses and hemorrhagic fever viruses in human and vector populations implemented since mid 2020 in eastern Senegal. Virological analyses highlighted the implication of sylvatic mosquito species in virus transmission. Genomic analysis showed a close relationship between the circulating strain in eastern Senegal, 2020, and another one from the West African lineage previously detected and sequenced two years ago from an unvaccinated Dutch traveler who visited the Gambia and Senegal before developing signs after returning to Europe. Moreover, genome analysis identified a 6-nucleotide deletion in the variable domain of the 3′UTR with potential impact on the biology of the viral strain that merits further investigations. Integrated surveillance of yellow fever virus but also of other arboviruses of public health interest is crucial in an ecosystem such as eastern Senegal.

scholarly journals Yellow fever virus is susceptible to sofosbuvir both in vitro and in vivo

2019 ◽  
Vol 13 (1) ◽  
pp. e0007072 ◽  
Author(s):  
Caroline S. de Freitas ◽  
Luiza M. Higa ◽  
Carolina Q. Sacramento ◽  
André C. Ferreira ◽  
Patrícia A. Reis ◽  
...  
Keyword(s):  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Fever Virus

CULTURE OF YELLOW-FEVER VIRUS IN VITRO

The Lancet ◽  
1940 ◽  
Vol 236 (6102) ◽  
pp. 163-164 ◽  
Author(s):  
G.M. Findlay ◽  
F.O. Maccallum
Keyword(s):  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Fever Virus

scholarly journals Mutations in the Yellow Fever Virus Nonstructural Protein NS2A Selectively Block Production of Infectious Particles

2002 ◽  
Vol 76 (10) ◽  
pp. 4773-4784 ◽  
Author(s):  
Beate M. Kümmerer ◽  
Charles M. Rice
Keyword(s):  
Amino Acids ◽  
Yellow Fever ◽  
Cleavage Site ◽  
Infectious Virus ◽  
Yellow Fever Virus ◽  
Nonstructural Protein ◽  
Virus Production ◽  
Fever Virus ◽  
Helicase Domain ◽  
Infected Cells

ABSTRACT Little is known about the function of flavivirus nonstructural protein NS2A. Two forms of NS2A are found in yellow fever virus-infected cells. Full-length NS2A (224 amino acids) is the product of cleavage at the NS1/2A and NS2A/2B sites. NS2Aα, a C-terminally truncated form of 190 amino acids, results from partial cleavage by the viral NS2B-3 serine protease at the sequence QK↓T within NS2A. Exchange of serine for lysine at this site (QKT→QST) blocks the production of both NS2Aα and infectious virus. The present study reveals that this defect is not at the level of RNA replication. Despite normal structural region processing, infectious particles containing genome RNA and capsid protein were not released from cells transfected with the mutant RNA. Nevertheless, production of subviral prM/M- and E-containing particles was unimpaired. The NS2A defect could be complemented in trans by providing NS1-2A or NS1-2Aα. However, trans complementation was not observed when the C-terminal lysine of NS1-2Aα was replaced with serine. In addition to true reversions, NS2Aα cleavage site mutations could be suppressed by two classes of second-site changes. The first class consisted of insertions at the NS2Aα cleavage site that restored its basic character and cleavability. A second class of suppressors occurred in the NS3 helicase domain, in which NS3 aspartate 343 was replaced with an uncharged residue (either valine, alanine, or glycine). These mutations in NS3 restored infectious-virus production in the absence of cleavage at the mutant NS2Aα site. Taken together, our results reveal an unexpected role for NS2A and NS3 in the assembly and/or release of infectious flavivirus particles.

scholarly journals High Fidelity of Yellow Fever Virus RNA Polymerase

2004 ◽  
Vol 78 (2) ◽  
pp. 1032-1038 ◽  
Author(s):  
Konstantin V. Pugachev ◽  
Farshad Guirakhoo ◽  
Simeon W. Ocran ◽  
Fred Mitchell ◽  
Megan Parsons ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Rna Polymerase ◽  
Yellow Fever ◽  
Error Rate ◽  
Yellow Fever Virus ◽  
Protein A ◽  
Fever Virus ◽  
Genome Replication ◽  
Virus Rna

ABSTRACT Three consecutive plaque purifications of four chimeric yellow fever virus-dengue virus (ChimeriVax-DEN) vaccine candidates against dengue virus types 1 to 4 were performed. The genome of each candidate was sequenced by the consensus approach after plaque purification and additional passages in cell culture. Our data suggest that the nucleotide sequence error rate for SP6 RNA polymerase used in the in vitro transcription step to initiate virus replication was as high as 1.34 × 10−4 per copied nucleotide and that the error rate of the yellow fever virus RNA polymerase employed by the chimeras for genome replication in infected cells was as low as 1.9 × 10−7 to 2.3 × 10−7. Clustering of beneficial mutations that accumulated after multiple virus passages suggests that the N-terminal part of the prM protein, a specific site in the middle of the E protein, and the NS4B protein may be essential for nucleocapsid-envelope interaction during flavivirus assembly.

scholarly journals THE ADAPTATION OF UNMODIFIED STRAINS OF YELLOW FEVER VIRUS TO CULTIVATION IN VITRO

1937 ◽  
Vol 65 (6) ◽  
pp. 801-808 ◽  
Author(s):  
Hugh H. Smith ◽  
Max Theiler
Keyword(s):  
Brain Tissue ◽  
Yellow Fever ◽  
Mouse Embryo ◽  
Yellow Fever Virus ◽  
Fever Virus ◽  
In Vitro Cultivation ◽  
Virus Content ◽  
Cultivation In Vitro ◽  
Embryo Brain

1. In a search for suitable tissues for the cultivation of yellow fever virus in vitro, mouse embryos were inoculated with this virus in utero. A titration for virus content of the various organs of the embryos indicated that the virus was present in the brain in greatest concentration. 2. Unmodified strains of yellow fever virus were readily adapted to cultivation in vitro in a medium consisting of minced mouse embryo brain tissue and Tyrode solution containing 10 per cent normal monkey serum. 3. After a continued cultivation in mouse embryo brain tissue cultures for twenty to twenty-five subcultures, these strains were readily adapted to cultivation in whole mouse embryo tissue medium. 4. There is evidence to indicate that a prolonged cultivation of the virus in mouse embryo brain medium increases its neurotropic properties. 5. Attempts to employ monkey tissues for in vitro cultivation of yellow fever virus gave entirely negative results.

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