Novel Flavivirus Attenuation Markers Identified in the Envelope Protein of Alfuy Virus

Westlake, Daniel; Bielefeldt‐Ohmann, Helle; Prow, Natalie A.; Hall, Roy A.

doi:10.3390/v13020147

Cited by 4 publications

(2 citation statements)

References 54 publications

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“…Other studies revealed that the Lys 70 residue was present in multiple commonly used SINV laboratory strains [51]. This phenomenon has been reproduced starting with low cell passage versions of RRV, Semliki Forest virus (SFV) and CHIKV alphaviruses and YFV, MVEV, DENV, WNV, JEV, and TBEV flaviviruses yielding a large panel of known loci associated with enhancement of GAG interaction after in vitro passage () () [53, 57, 60, 66, 72, 73, 75, 85, 88, 93–97]. These findings have utility in live attenuated vaccine design and also may allow determination of differences in naturally acquired and cell-adaptive GAG binding characteristics.…”

Section: Introductionmentioning

confidence: 94%

Glycosaminoglycan binding by arboviruses: a cautionary tale

Alcorn

Klimstra

2022

Journal of General Virology

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Arboviruses are medically important arthropod-borne viruses that cause a range of diseases in humans from febrile illness to arthritis, encephalitis and hemorrhagic fever. Given their transmission cycles, these viruses face the challenge of replicating in evolutionarily divergent organisms that can include ticks, flies, mosquitoes, birds, rodents, reptiles and primates. Furthermore, their cell attachment receptor utilization may be affected by the opposing needs for generating high and sustained serum viremia in vertebrates such that virus particles are efficiently collected during a hematophagous arthropod blood meal but they must also bind sufficiently to cellular structures on divergent organisms such that productive infection can be initiated and viremia generated. Sulfated polysaccharides of the glycosaminoglycan (GAG) groups, primarily heparan sulfate (HS), have been identified as cell attachment moieties for many arboviruses. Original identification of GAG binding as a phenotype of arboviruses appeared to involve this attribute arising solely as a consequence of adaptation of virus isolates to growth in cell culture. However, more recently, naturally circulating strains of at least one arbovirus, eastern equine encephalitis, have been shown to bind HS efficiently and the GAG binding phenotype continues to be associated with arbovirus infection in published studies. If GAGs are attachment receptors for many naturally circulating arboviruses, this could lead to development of broad-spectrum antiviral therapies through blocking of the virus–GAG interaction. This review summarizes the available data for GAG/HS binding as a phenotype of naturally circulating arbovirus strains emphasizing the importance of avoiding tissue culture amplification and artifactual phenotypes during their isolation.

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Section: Introductionmentioning

confidence: 94%

Glycosaminoglycan binding by arboviruses: a cautionary tale

Alcorn

Klimstra

2022

Journal of General Virology

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“…A GAG molecule is a negatively charged polysaccharide, well known as an attenuation factor of flaviviruses [ 23 ]. GAG-binding sites are mainly located in the domain III of the E protein and they continue to be discovered [ 24 ]. Moreover, there is a report on a putative GAG-binding site (E138 in Japanese encephalitis virus) in the domain I [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Genomic Determinants Potentially Associated with Clinical Manifestations of Human-Pathogenic Tick-Borne Flaviviruses

Bondaryuk

Kulakova

Potapova

et al. 2022

IJMS

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The tick-borne flavivirus group contains at least five species that are pathogenic to humans, three of which induce encephalitis (tick-borne encephalitis virus, louping-ill virus, Powassan virus) and another two species induce hemorrhagic fever (Omsk hemorrhagic fever virus, Kyasanur Forest disease virus). To date, the molecular mechanisms responsible for these strikingly different clinical forms are not completely understood. Using a bioinformatic approach, we performed the analysis of each amino acid (aa) position in the alignment of 323 polyprotein sequences to calculate the fixation index (Fst) per site and find the regions (determinants) where sequences belonging to two designated groups were most different. Our algorithm revealed 36 potential determinants (Fst ranges from 0.91 to 1.0) located in all viral proteins except a capsid protein. In an envelope (E) protein, most of the determinants were located on the virion surface regions (domains II and III) and one (absolutely specific site 457) was located in the transmembrane region. Another 100% specific determinant site (E63D) with Fst = 1.0 was located in the central hydrophilic domain of the NS2b, which mediates NS3 protease activity. The NS5 protein contains the largest number of determinants (14) and two of them are absolutely specific (T226S, E290D) and are located near the RNA binding site 219 (methyltransferase domain) and the extension structure. We assume that even if not absolutely, highly specific sites, together with absolutely specific ones (Fst = 1.0) can play a supporting role in cell and tissue tropism determination.

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Emerging mosquito-borne flaviviruses

Nelson,

Ploss

2024

mBio

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Flaviviruses comprise a genus of enveloped, positive-sense, single-stranded RNA viruses typically transmitted between susceptible and permissive hosts by arthropod vectors. Established flavivirus threats include dengue viruses (DENV), yellow fever virus (YFV), Zika virus (ZIKV), and West Nile virus (WNV), which continue to cause over 400 million infections annually and are significant global health and economic burdens. Additionally, numerous closely related but largely understudied viruses circulate in animals and can conceivably emerge in human populations. Previous flaviviruses that were recognized to have this potential include ZIKV and WNV, which only became extensively studied after causing major outbreaks in humans. More than 50 species exist within the flavivirus genus, which can be further classified as mosquito-borne, tick-borne, insect-specific, or with no known vector. Historically, many of these flaviviruses originated in Africa and have mainly affected tropical and subtropical regions due to the ecological niche of mosquitoes. However, climate change, as well as vector and host migration, has contributed to geographical expansion, thereby posing a potential risk to global populations. For the purposes of this minireview, we focus on the mosquito-borne subgroup and highlight viruses that cause significant pathology or lethality in at least one animal species and/or have demonstrated an ability to infect humans. We discuss current knowledge of these viruses, existing animal models to study their pathogenesis, and potential future directions. Emerging viruses discussed include Usutu virus (USUV), Wesselsbron virus (WSLV), Spondweni virus (SPOV), Ilheus virus (ILHV), Rocio virus (ROCV), Murray Valley encephalitis virus (MVEV), and Alfuy virus (ALFV).

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Novel Flavivirus Attenuation Markers Identified in the Envelope Protein of Alfuy Virus

Cited by 4 publications

References 54 publications

Glycosaminoglycan binding by arboviruses: a cautionary tale

Glycosaminoglycan binding by arboviruses: a cautionary tale

Genomic Determinants Potentially Associated with Clinical Manifestations of Human-Pathogenic Tick-Borne Flaviviruses

Emerging mosquito-borne flaviviruses

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