scholarly journals The secretory fate of flavivirus NS1 in mosquito cells is influenced by the caveolin binding domain

2019 ◽  
Author(s):  
Romel Rosales Ramirez ◽  
Juan E. Ludert
Keyword(s):  
Yellow Fever ◽  
Zika Virus ◽  
Yellow Fever Virus ◽  
Binding Domain ◽  
Expression Vectors ◽  
Mosquito Vector ◽  
Structural Protein ◽  
Aromatic Residues ◽  
Secretion Pathway ◽  
Mosquito Cells

ABSTRACTFlaviviruses of major medical importance worldwide such as dengue (DENV), Zika (ZIKV), and yellow fever (YFV) viruses are transmitted by mosquitoes Aedes sp. The non-structural protein 1 (NS1) of these flaviviruses is secreted from the infected cells using different secretion routes depending on the cell and virus nature. The NS1 of DENV and ZIKV contain in the hydrophobic region a conserved caveolin binding domain (CBD) (ΦXXΦXXXXΦ), which is not conserved in YFV NS1. To ascertain the role of the CBD in the secretory route followed by flavivirus NS1, expression vectors for the NS1 of DENV2, ZIKV and YFV were constructed. Using site-directed mutagenesis, substitutions were made in the aromatic residues within CBD; in addition, the full domain was replaced by those of other flaviviruses, creating chimeras in the CBD of NS1. Substitutions of the aromatic residues to Ala or Thr, or CBD chimeras, results in increased sensitivity of NS1 secretion to brefeldin A treatment, indicating a change to a classical secretion pathway. Likewise, the insertion of the DENV/ZIKV CBD into the recombinant Gaussia-Luciferase results in a loss of sensitivity to BFA treatment, in luciferase secretion. These results suggest that the CBD sequence is a molecular determinant for the unconventional secretory route followed by DENV and ZIKV NS1 in mosquito cells. However, the cellular components that recognize the CBD in the NS1 of DENV and ZIKV and redirect them to an unconventional route and if this secretion route confers unique functions to NS1 within the vector mosquito are aspects currently unknown.ImportanceFlaviviruses are an important cause of mosquito borne diseases to humans. We have previously demonstrated that the non-structural protein 1 from dengue and zika virus are secreted efficiently from mosquito cells using an unconventional route, that depends on caveolin and molecular chaperones. In this work, we show evidence indicating that a caveolin binding domain, well conserved and exposed in dengue and Zika virus NS1, but absent in other flaviviruses such as yellow fever virus or West Nile virus, is important in determining the unconventional secretion pathway followed by dengue and zika virus NS1 in mosquito cells. The unique secretory pathway followed by NS1 in mosquito cells may result in distinctive viral-cellular protein associations required to facilitate viral infection in the mosquito vector. To identify viral and cellular elements that could disturb the traffic of dengue and Zika virus NS1 may be important to design of strategies for vector control.

scholarly journals Zika Virus: A Clinical Review

KYAMC Journal ◽  
2017 ◽  
Vol 7 (1) ◽  
pp. 719-725
Author(s):  
Md Daharul Islam ◽  
SM Tajdit Rahman ◽  
Khaleda Akhter ◽  
Md Azizul Hoque ◽  
Anannya Roy ◽  
...  
Keyword(s):  
Yellow Fever ◽  
Zika Virus ◽  
Yellow Fever Virus ◽  
Virus Disease ◽  
Specific Treatment ◽  
Abrupt Onset ◽  
Fever Virus ◽  
Control Measures ◽  
Disease Treatment ◽  
Antibodies Detection

Zika virus is a flavivirus related to Dengue virus, yellow fever virus and West Nile virus. It is considered an emerging arbovirus transmitted by mosquito of the genus Aedes. Its first description took place in 1947 in the Zika Forest in Uganda, isolated on Rhesus monkey used as bait to study the yellow fever virus. Clinical picture is characterized as a 'dengue-like' syndrome, with abrupt onset of fever; and an early onset of evanescent rash, often pruritic. Occasionally the disease has been associated with Guillain-Barré syndrome. The diagnosis can be performed by PCR or by IgG and IgM antibodies detection. No specific treatment or vaccine is available for Zika virus disease. Treatment is generally supportive. Control measures are same for dengue and chikungunya based mostly on health education and vector control.KYAMC Journal Vol. 7, No.-1, Jul 2016, Page 719-725

Simultaneous detection of Dengue virus, Chikungunya virus, Zika virus, Yellow fever virus and West Nile virus

2019 ◽  
Vol 268 ◽  
pp. 53-55 ◽  
Author(s):  
José A. Boga ◽  
Marta E. Alvarez-Arguelles ◽  
Susana Rojo-Alba ◽  
Mercedes Rodríguez ◽  
María de Oña ◽  
...  
Keyword(s):  
West Nile Virus ◽  
Dengue Virus ◽  
Yellow Fever ◽  
Zika Virus ◽  
Chikungunya Virus ◽  
Yellow Fever Virus ◽  
Simultaneous Detection ◽  
Fever Virus ◽  
West Nile ◽  
Virus Zika

Comparison of Genetic Variations in Zika Virus Isolated From Different Geographic Regions

2019 ◽  
Vol 14 (3) ◽  
pp. 29-39
Author(s):  
Jooyeon Park ◽  
Jinhwa Jang ◽  
Insung Ahn
Keyword(s):  
West Nile Virus ◽  
Yellow Fever ◽  
Zika Virus ◽  
Complete Genome Sequence ◽  
Yellow Fever Virus ◽  
Clinical Progression ◽  
The World ◽  
Membrane Envelope ◽  
Geographic Regions ◽  
Effective Drugs

The Zika virus (ZIKV) belongs to the genus Flavivirus, together with Dengue virus, yellow fever virus, and West Nile virus. The virus, which was first found in Africa in 1947, has spread across the world owing to a lack of effective drugs or vaccines. The complete genome sequence of ZIKV is now available; it includes three structural and seven non-structure genes arranged in the order of capsid, pre-membrane, envelope, NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5. Two geographically distinct lineages are known, i.e., Asian and African, but ZIKV exhibits differences in clinical progression among regions.

scholarly journals Variable Inhibition of Zika Virus Replication by Different Wolbachia Strains in Mosquito Cell Cultures

2017 ◽  
Vol 91 (14) ◽  
Author(s):  
Michaela J. Schultz ◽  
Sharon Isern ◽  
Scott F. Michael ◽  
Ronald B. Corley ◽  
John H. Connor ◽  
...  
Keyword(s):  
Virus Replication ◽  
Zika Virus ◽  
Western Hemisphere ◽  
Mosquito Cell ◽  
Mosquito Vector ◽  
Viral Inhibition ◽  
Virus Growth ◽  
Content Type ◽  
Bacterial Endosymbiont ◽  
Mosquito Cells

ABSTRACT Mosquito-borne arboviruses are a major source of human disease. One strategy to reduce arbovirus disease is to reduce the mosquito's ability to transmit virus. Mosquito infection with the bacterial endosymbiont Wolbachia pipientis wMel is a novel strategy to reduce Aedes mosquito competency for flavivirus infection. However, experiments investigating cyclic environmental temperatures have shown a reduction in maternal transmission of wMel, potentially weakening the integration of this strain into a mosquito population relative to that of other Wolbachia strains. Consequently, it is important to investigate additional Wolbachia strains. All Zika virus (ZIKV) suppression studies are limited to the wMel Wolbachia strain. Here we show ZIKV inhibition by two different Wolbachia strains: wAlbB (isolated from Aedes albopictus mosquitoes) and wStri (isolated from the planthopper Laodelphax striatellus) in mosquito cells. Wolbachia strain wStri inhibited ZIKV most effectively. Single-cycle infection experiments showed that ZIKV RNA replication and nonstructural protein 5 translation were reduced below the limits of detection in wStri-containing cells, demonstrating early inhibition of virus replication. ZIKV replication was rescued when Wolbachia was inhibited with a bacteriostatic antibiotic. We observed a partial rescue of ZIKV growth when Wolbachia-infected cells were supplemented with cholesterol-lipid concentrate, suggesting competition for nutrients as one of the possible mechanisms of Wolbachia inhibition of ZIKV. Our data show that wAlbB and wStri infection causes inhibition of ZIKV, making them attractive candidates for further in vitro mechanistic and in vivo studies and future vector-centered approaches to limit ZIKV infection and spread. IMPORTANCE Zika virus (ZIKV) has swiftly spread throughout most of the Western Hemisphere. This is due in large part to its replication in and spread by a mosquito vector host. There is an urgent need for approaches that limit ZIKV replication in mosquitoes. One exciting approach for this is to use a bacterial endosymbiont called Wolbachia that can populate mosquito cells and inhibit ZIKV replication. Here we show that two different strains of Wolbachia, wAlbB and wStri, are effective at repressing ZIKV in mosquito cell lines. Repression of virus growth is through the inhibition of an early stage of infection and requires actively replicating Wolbachia. Our findings further the understanding of Wolbachia viral inhibition and provide novel tools that can be used in an effort to limit ZIKV replication in the mosquito vector, thereby interrupting the transmission and spread of the virus.

scholarly journals Colonized Sabethes cyaneus, a Sylvatic New World Mosquito Species, Shows a Low Vector Competence for Zika Virus Relative to Aedes aegypti

Viruses ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 434 ◽  
Author(s):  
Ajit K. Karna ◽  
Sasha R. Azar ◽  
Jessica A. Plante ◽  
Rumei Yun ◽  
Nikos Vasilakis ◽  
...  
Keyword(s):  
Aedes Aegypti ◽  
Yellow Fever ◽  
Zika Virus ◽  
New World ◽  
Yellow Fever Virus ◽  
Vector Competence ◽  
Mosquito Species ◽  
Sylvatic Cycle ◽  
Post Feeding ◽  
Body Compartments

The introduction of Zika virus (ZIKV) to the Americas raised concern that the virus would spill back from human transmission, perpetuated by Aedes aegypti, into a sylvatic cycle maintained in wildlife and forest-living mosquitoes. In the Americas, Sabethes species are vectors of sylvatic yellow fever virus (YFV) and are therefore candidate vectors of a sylvatic ZIKV cycle. To test the potential of Sabethes cyaneus to transmit ZIKV, Sa. cyaneus and Ae. aegypti were fed on A129 mice one or two days post-infection (dpi) with a ZIKV isolate from Mexico. Sa. cyaneus were sampled at 3, 4, 5, 7, 14, and 21 days post-feeding (dpf) and Ae. aegypti were sampled at 14 and 21 dpf. ZIKV was quantified in mosquito bodies, legs, and saliva to measure infection, dissemination, and potential transmission, respectively. Of 69 Sa. cyaneus that fed, ZIKV was detected in only one, in all body compartments, at 21 dpf. In contrast, at 14 dpf 100% of 20 Ae. aegypti that fed on mice at 2 dpi were infected and 70% had virus in saliva. These data demonstrate that Sa. cyaneus is a competent vector for ZIKV, albeit much less competent than Ae. aegypti.

scholarly journals Host-Specific NS5 Ubiquitination Determines Yellow Fever Virus Tropism

2019 ◽  
Vol 93 (14) ◽  
Author(s):  
Lisa Miorin ◽  
Maudry Laurent-Rolle ◽  
Giuseppe Pisanelli ◽  
Pierre Hendrick Co ◽  
Randy A. Albrecht ◽  
...  
Keyword(s):  
Animal Models ◽  
Mouse Model ◽  
Yellow Fever ◽  
Zika Virus ◽  
Yellow Fever Virus ◽  
Disease Model ◽  
Fever Virus ◽  
Type I ◽  
Human Pathogens ◽  
Immunocompetent Mouse

ABSTRACT The recent yellow fever virus (YFV) epidemic in Brazil in 2017 and Zika virus (ZIKV) epidemic in 2015 serve to remind us of the importance of flaviviruses as emerging human pathogens. With the current global flavivirus threat, there is an urgent need for antivirals and vaccines to curb the spread of these viruses. However, the lack of suitable animal models limits the research questions that can be answered. A common trait of all flaviviruses studied thus far is their ability to antagonize interferon (IFN) signaling so as to enhance viral replication and dissemination. Previously, we reported that YFV NS5 requires the presence of type I IFN (IFN-α/β) for its engagement with human signal transducer and activator of transcription 2 (hSTAT2). In this manuscript, we report that like the NS5 proteins of ZIKV and dengue virus (DENV), YFV NS5 protein is able to bind hSTAT2 but not murine STAT2 (mSTAT2). Contrary to what has been demonstrated with ZIKV NS5 and DENV NS5, replacing mSTAT2 with hSTAT2 cannot rescue the YFV NS5-STAT2 interaction, as YFV NS5 is also unable to interact with hSTAT2 in murine cells. We show that the IFN-α/β-dependent ubiquitination of YFV NS5 that is required for STAT2 binding in human cells is absent in murine cells. In addition, we demonstrate that mSTAT2 restricts YFV replication in vivo. These data serve as further impetus for the development of an immunocompetent mouse model that can serve as a disease model for multiple flaviviruses. IMPORTANCE Flaviviruses such as yellow fever virus (YFV), Zika virus (ZIKV), and dengue virus (DENV) are important human pathogens. A common flavivirus trait is the antagonism of interferon (IFN) signaling to enhance viral replication and spread. We report that like ZIKV NS5 and DENV NS5, YFV NS5 binds human STAT2 (hSTAT2) but not mouse STAT2 (mSTAT2), a type I IFN (IFN-α/β) pathway component. Additionally, we show that contrary to what has been demonstrated with ZIKV NS5 and DENV NS5, YFV NS5 is unable to interact with hSTAT2 in murine cells. We demonstrate that mSTAT2 restricts YFV replication in mice and that this correlates with a lack of IFN-α/β-induced YFV NS5 ubiquitination in murine cells. The lack of suitable animal models limits flavivirus pathogenesis, vaccine, and drug research. These data serve as further impetus for the development of an immunocompetent mouse model that can serve as a disease model for multiple flaviviruses.

Adaptation of yellow fever virus 17D to Vero cells is associated with mutations in structural and non-structural protein genes

2013 ◽  
Vol 176 (1-2) ◽  
pp. 280-284 ◽  
Author(s):  
David W.C. Beasley ◽  
Merribeth Morin ◽  
Ashley R. Lamb ◽  
Edward Hayman ◽  
Douglas M. Watts ◽  
...  
Keyword(s):  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Vero Cells ◽  
Fever Virus ◽  
Structural Protein

scholarly journals Biological Characteristics and Patterns of Codon Usage Evolution for the African Genotype Zika Virus

Viruses ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1306
Author(s):  
Martin Faye ◽  
Naimah Zein ◽  
Cheikh Loucoubar ◽  
Manfred Weidmann ◽  
Ousmane Faye ◽  
...  
Keyword(s):  
Codon Usage ◽  
Zika Virus ◽  
Yellow Fever Virus ◽  
Temporal Trends ◽  
Biological Properties ◽  
Host Tropism ◽  
Mosquito Cells ◽  
Mosquito Cell Lines ◽  
The Individual

We investigated temporal trends of codon usage changes for different host species to determine their importance in Zika virus (ZIKV) evolution. Viral spillover resulting from the potential of codon adaptation to host genome was also assessed for the African genotype ZIKV in comparison to the Asian genotype. To improve our understanding on its zoonotic maintenance, we evaluated in vitro the biological properties of the African genotype ZIKV in vertebrate and mosquito cell lines. Analyses were performed in comparison to Yellow fever virus (YFV). Despite significantly lower codon adaptation index trends than YFV, ZIKV showed evident codon adaptation to vertebrate hosts, particularly for the green African monkey Chlorocebus aethiops. PCA and CAI analyses at the individual ZIKV gene level for both human and Aedes aegypti indicated a clear distinction between the two genotypes. African ZIKV isolates showed higher virulence in mosquito cells than in vertebrate cells. Their higher replication in mosquito cells than African YFV confirmed the role of mosquitoes in the natural maintenance of the African genotype ZIKV. An analysis of individual strain growth characteristics indicated that the widely used reference strain MR766 replicates poorly in comparison to African ZIKV isolates. The recombinant African Zika virus strain ArD128000*E/NS5 may be a good model to include in studies on the mechanism of host tropism, as it cannot replicate in the tested vertebrate cell line.

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