scholarly journals Polycistronic Genome Segment Evolution and Gain and Loss of FAST Protein Function during Fusogenic Orthoreovirus Speciation

Viruses ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 702
Author(s):  
Yiming Yang ◽  
Gerard Gaspard ◽  
Nichole McMullen ◽  
Roy Duncan
Keyword(s):  
Protein Function ◽  
Phylogenetic Analyses ◽  
Protein A ◽  
Virus Transmission ◽  
Syncytium Formation ◽  
Virus Family ◽  
Enveloped Virus ◽  
Gain And Loss ◽  
Fiber Proteins ◽  
Avian Reoviruses

The Reoviridae family is the only non-enveloped virus family with members that use syncytium formation to promote cell–cell virus transmission. Syncytiogenesis is mediated by a fusion-associated small transmembrane (FAST) protein, a novel family of viral membrane fusion proteins. Previous evidence suggested the fusogenic reoviruses arose from an ancestral non-fusogenic virus, with the preponderance of fusogenic species suggesting positive evolutionary pressure to acquire and maintain the fusion phenotype. New phylogenetic analyses that included the atypical waterfowl subgroup of avian reoviruses and recently identified new orthoreovirus species indicate a more complex relationship between reovirus speciation and fusogenic capacity, with numerous predicted internal indels and 5’-terminal extensions driving the evolution of the orthoreovirus’ polycistronic genome segments and their encoded FAST and fiber proteins. These inferred recombination events generated bi- and tricistronic genome segments with diverse gene constellations, they occurred pre- and post-orthoreovirus speciation, and they directly contributed to the evolution of the four extant orthoreovirus FAST proteins by driving both the gain and loss of fusion capability. We further show that two distinct post-speciation genetic events led to the loss of fusion in the waterfowl isolates of avian reovirus, a recombination event that replaced the p10 FAST protein with a heterologous, non-fusogenic protein and point substitutions in a conserved motif that destroyed the p10 assembly into multimeric fusion platforms.

Coronavirus: history, genome structure and pathogenesis

Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Poonam B ◽  
Prabhjot Kaur Gill
Keyword(s):  
Genome Structure ◽  
Public Health Research ◽  
Replication Process ◽  
Virus Family ◽  
Enveloped Virus ◽  
Target Organs ◽  
Transcription Process ◽  
Recent Emergence ◽  
The Family ◽  
Discontinuous Transcription

Background: The positive sense and inordinate large RNA genome are enclosed by helical nuceocapsids along with an outermost layer belongs to the family Coronaviridae. The phylogenetic tree of this family has been quartered into Class1 as alpha, Class 2 as beta, Class 3 as gamma and Class 4 as delta CoV. The mammalian respiratory and gastrointestinal tracts are the main target organs of this enveloped virus with misperceived mechanisms. The relevance of this virus family has considerably increased by the dint of recent emergence of the Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS), which are caused by viruses belonging to the beta-CoV group. Aim: Aforesaid illustrations of emergence of coronavirus diseases over the past two decades, SARS (2002 and 2003) and MERS (2012 to present) - the ongoing COVID-19 outbreak has pressurized the WHO to take innovative measures for public health, research and medical communities. The aim of the present review is to have proficiency in coronavirus replication and transcription process which is still in its infancy. Conclusion: An outcome of epidemics, it is being recognized as one of the most advancing viruses by the virtue of high genomic nucleotide substitution rates and recombination. The hallmark of coronavirus replication is discontinuous transcription resulting in the production of multiple subgenomic mRNAs having sequences complementary to both ends of the genome. Therefore, complete genome sequence of coronavirus will be used as frame of reference for knowing this classical phenomenon of RNA replication process. Finally, research on the pathogenesis of coronaviruses and the host immunopathological response will aid in designing vaccines and minimizing mortality rate.

scholarly journals Molecular Epidemiology and Whole-Genome Analysis of Bovine Foamy Virus in Japan

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1017
Author(s):  
Hirohisa Mekata ◽  
Tomohiro Okagawa ◽  
Satoru Konnai ◽  
Takayuki Miyazawa
Keyword(s):  
Phylogenetic Analyses ◽  
Foamy Virus ◽  
Pcr Analysis ◽  
Whole Genome ◽  
Genome Sequences ◽  
Whole Genome Analysis ◽  
Virus Family ◽  
Bovine Foamy Virus ◽  
Novel Genotype

Bovine foamy virus (BFV) is a member of the foamy virus family in cattle. Information on the epidemiology, transmission routes, and whole-genome sequences of BFV is still limited. To understand the characteristics of BFV, this study included a molecular survey in Japan and the determination of the whole-genome sequences of 30 BFV isolates. A total of 30 (3.4%, 30/884) cattle were infected with BFV according to PCR analysis. Cattle less than 48 months old were scarcely infected with this virus, and older animals had a significantly higher rate of infection. To reveal the possibility of vertical transmission, we additionally surveyed 77 pairs of dams and 3-month-old calves in a farm already confirmed to have BFV. We confirmed that one of the calves born from a dam with BFV was infected. Phylogenetic analyses revealed that a novel genotype was spread in Japan. In conclusion, the prevalence of BFV in Japan is relatively low and three genotypes, including a novel genotype, are spread in Japan.

The CD4+ T-cell response to adenovirus is focused against conserved residues within the hexon protein

2007 ◽  
Vol 88 (9) ◽  
pp. 2417-2425 ◽  
Author(s):  
David Onion ◽  
Laura J. Crompton ◽  
Donald W. Milligan ◽  
Paul A. H. Moss ◽  
Steven P. Lee ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
Protein A ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
T Cell Epitopes ◽  
Hexon Protein ◽  
Healthy Donors ◽  
Fiber Proteins

Adenovirus is a significant pathogen in immunocompromised patients and is widely utilized as a gene delivery vector, so a detailed understanding of the human immune response to adenovirus infection is critical. This study characterized the adenovirus-specific CD4+ T-cell response of healthy donors by incubation with whole virus or with individual hexon and fiber proteins. Adenovirus-specific CD4+ T cells averaged 0.26 % of the CD4+ T-cell pool and were detectable in all donors. T cells recognizing the highly conserved hexon protein accounted for 0.09 %, whereas no response was observed against the fiber protein. A panel of hexon-specific CD4+ T-cell clones was generated and shown to lyse targets infected with adenovirus from different serotypes and species. Three CD4 T-cell epitopes are described, which map to highly conserved regions of the hexon protein.

scholarly journals A FOUNDER EFFECT LED EARLY SARS-COV-2 TRANSMISSION IN SPAIN

2020 ◽  
Author(s):  
Francisco Díez-Fuertes ◽  
María Iglesias-Caballero ◽  
Javier García Pérez ◽  
Sara Monzón ◽  
Pilar Jiménez ◽  
...  
Keyword(s):  
Founder Effect ◽  
Phylogenetic Analyses ◽  
Protein A ◽  
Spike Protein ◽  
Recent Common Ancestor ◽  
Whole Genome ◽  
Whole Genome Analysis ◽  
Most Recent Common Ancestor ◽  
Fitness Advantage

SARS-CoV-2 whole-genome analysis has identified five large clades worldwide, emerged in 2019 (19A and 19B) and in 2020 (20A, 20B and 20C). This study aims to analyze the diffusion of SARS-CoV-2 in Spain using maximum likelihood phylogenetic and Bayesian phylodynamic analyses. The most recent common ancestor (MRCA) of the SARS-CoV-2 pandemic was estimated in Wuhan, China, around November 24, 2019. Phylogenetic analyses of the first 12,511 SARS-CoV-2 whole genome sequences obtained worldwide, including 290 from 11 different regions of Spain, revealed 62 independent introductions of the virus in the country. Most sequences from Spain were distributed in clades characterized by D614G substitution in S gene (20A, 20B and 20C) and L84S substitution in ORF8 (19B) with 163 and 118 sequences, respectively, with the remaining sequences branching in 19A. A total of 110 (38%) sequences from Spain grouped in four different monophyletic clusters of 20A clade (20A-Sp1 and 20A-Sp2) and 19B clade (19B-Sp1 and 19B-Sp2) along with sequences from 29 countries worldwide. The MRCA of 19A-Sp1, 20A-Sp1, 19A-Sp2 and 20A-Sp2 clusters were estimated in Spain around January 21 and 29, and February 6 and 17, 2020, respectively. The prevalence of 19B clade in Spain (40%) was by far higher than in any other European country during the first weeks of the epidemic, probably by a founder effect. However, this variant was replaced by G614-bearing viruses in April. In vitro assays showed an enhanced infectivity of pseudotyped virions displaying G614 substitution compared with D614, suggesting a fitness advantage of D614G. IMPORTANCE Multiple SARS-CoV-2 introductions have been detected in Spain and at least four resulted in the emergence of locally transmitted clusters originated not later than mid-February, with further dissemination to many other countries around the world and a few weeks before the explosion of COVID-19 cases detected in Spain during the first week of March. The majority of the earliest variants detected in Spain branched in 19B clade (D614 viruses), which was the most prevalent clade during the first weeks of March, pointing to a founder effect. However, from mid-March to June, 2020, G614-bearing viruses (20A, 20B and 20C clades) overcame D614 variants in Spain, probably as a consequence of an evolutionary advantage of this substitution in the spike protein. A higher infectivity of G614-bearing viruses compared to D614 variants was detected, suggesting that this substitution in SARS-CoV-2 spike protein could be behind the variant shift observed in Spain.

scholarly journals Identification of a Novel Deltavirus in Boa Constrictors

mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
Udo Hetzel ◽  
Leonóra Szirovicza ◽  
Teemu Smura ◽  
Barbara Prähauser ◽  
Olli Vapalahti ◽  
...  
Keyword(s):  
Horizontal Transmission ◽  
Circular Rna ◽  
Rt Pcr ◽  
Hepatitis D ◽  
Virus Family ◽  
Content Type ◽  
Enveloped Virus ◽  
Satellite Virus ◽  
Boa Constrictor ◽  
Coding Strategy

ABSTRACT Hepatitis D virus (HDV) forms the genus Deltavirus unassigned to any virus family. HDV is a satellite virus and needs hepatitis B virus (HBV) to make infectious particles. Deltaviruses are thought to have evolved in humans, since for a long time, they had not been identified elsewhere. Herein we report, prompted by the recent discovery of an HDV-like agent in birds, the identification of a deltavirus in snakes (Boa constrictor) designated snake HDV (sHDV). The circular 1,711-nt RNA genome of sHDV resembles human HDV (hHDV) in its coding strategy and size. We discovered sHDV during a metatranscriptomic study of brain samples of a Boa constrictor breeding pair with central nervous system signs. Applying next-generation sequencing (NGS) to brain, blood, and liver samples from both snakes, we did not find reads matching hepadnaviruses. Sequence comparison showed the snake delta antigen (sHDAg) to be 55% and 37% identical to its human and avian counterparts. Antiserum raised against recombinant sHDAg was used in immunohistology and demonstrated a broad viral target cell spectrum, including neurons, epithelial cells, and leukocytes. Using RT-PCR, we also detected sHDV RNA in two juvenile offspring and in a water python (Liasis mackloti savuensis) in the same snake colony, potentially indicating vertical and horizontal transmission. Screening of 20 randomly selected boas from another breeder by RT-PCR revealed sHDV infection in three additional snakes. The observed broad tissue tropism and the failure to detect accompanying hepadnavirus suggest that sHDV could be a satellite virus of a currently unknown enveloped virus. IMPORTANCE So far, the only known example of deltaviruses is the hepatitis delta virus (HDV). HDV is speculated to have evolved in humans, since deltaviruses were until very recently found only in humans. Using a metatranscriptomic sequencing approach, we found a circular RNA, which resembles that of HDV in size and coding strategy, in a snake. The identification of similar deltaviruses in distantly related species other than humans indicates that the previously suggested hypotheses on the origins of deltaviruses need to be updated. It is still possible that the ancestor of deltaviruses emerged from cellular RNAs; however, it likely would have happened much earlier in evolution than previously thought. These findings open up completely new avenues in evolution and pathogenesis studies of deltaviruses.

Discovery and genome characterization of a new Nepovirus infecting grapevine

Plant Disease ◽  
2020 ◽  
Author(s):  
Maher Al Rwahnih ◽  
Olufemi Joseph Alabi ◽  
Min Sook Hwang ◽  
Tongyan Tian ◽  
Dimitre Mollov ◽  
...  
Keyword(s):  
High Throughput Sequencing ◽  
Phylogenetic Analyses ◽  
Virus Transmission ◽  
Amino Acid Sequences ◽  
Molecular Characteristics ◽  
Vitis Vinifera L ◽  
Sequencing Analysis ◽  
Biological Index ◽  
Chenopodium Amaranticolor ◽  
Sequence Contigs

In 2012, dormant canes of a proprietary wine grape (Vitis vinifera L.) accession were included in the collection of the University of California-Davis Foundation Plant Services. No virus-like symptoms were elicited when bud chips from propagated own-rooted canes of the accession were graft-inoculated onto a panel of biological index grape varieties. However, chlorotic ring symptoms were observed on sap inoculated Chenopodium amaranticolor Coste & A. Rein and C. quinoa Willd. plants, indicating the presence of a mechanically transmissible virus. Transmission electron microscopy of virus preps from symptomatic C. quinoa revealed spherical, non-enveloped virions of ~27 nm in diameter. And nepovirus-like haplotypes of sequence contigs were detected in both the source grape accession and recipient C. quinoa plants using high throughput sequencing analysis. A novel bipartite nepovirus-like genome was assembled from these contigs and the termini of each RNA segment were verified by RACE assays. The RNA1 (7,186-nt) of the virus encode a large polyprotein P1 of 231.1 kDa while the RNA2 (4,460-nt) also encode a large polyprotein P2 of 148.9 kDa. Each of the polyadenylated RNA segment is flanked by 5′- (RNA1=156-nt; RNA2=170-nt) and 3′- (RNA1=834-nt; RNA2=261-nt) untranslated region sequences that shared >90% identities between their corresponding sequences. Maximum-likelihood phylogenetic analyses of the conserved Pro-Pol amino acid sequences of Secoviridae species revealed the clustering of the new virus within the nepovirus clade. Considering its biological and molecular characteristics, and based on current criteria, we propose that the novel virus, named as grapevine nepovirus A (GNVA), be assigned as a member of the genus Nepovirus.

O-β-GlcNAcylation, Chloroquine and 2-Hydroxybenzohydrazine May Hamper SARS-CoV-2 entry to Human via Inhibition of ACE2 Phosphorylation at Ser787 but Also Induce Disruption of Virus-ACE2 Binding

2020 ◽  
Author(s):  
Waqar Ahmad ◽  
Khadija Shabbiri ◽  
Nazarul Islam
Keyword(s):  
Human Body ◽  
Virus Entry ◽  
Critical Role ◽  
Virus Transmission ◽  
Binding Domain ◽  
Host Cells ◽  
Phosphoryl Group ◽  
Post Translational Modification ◽  
Virus Family ◽  
Downstream Signaling

The novel coronavirus COVID- 19 disease is extremely contagious and has been spread worldwide. First COVID-19 case was identified in December, 2019 and within three months, more than one million affected cases and over 65,000 deaths have been reported. SARS-coronavirus 2 (SARS-CoV-2) also known as 2019-nCoV is a causative agent of COVID-19 disease and belongs to the SARS CoV (Severe Acute Respiratory Syndrome corona virus) family. The SARS-CoV-2 enters the human body by binding its viral surface spike protein with the host angiotensin-converting enzyme 2 (ACE2) receptors and cause infection. To prevent the virus entry and its transmission in the human body, we focused on the two domains of ACE2: i) the N-terminal extracellular binding domain (18-740 residues) reported for coronavirus spike interaction, and ii) the C-terminal cytoplasmic region (762-805 residues) to prevent the virus transmission. Therefore, we proposed: i) inhibition of receptor binding domain (RBD) of SARS-CoV-2 and human ACE2 protein may prevent the virus entry to the host and ii) inhibition of phosphorylation at Ser-787 of ACE2 protein may prevent the transmission of the virus in the COVID-19 patients. In the past, the critical role of Ser 787 in human ACE2 protein has been experimentally verified in SARS-CoV transmission, that upon binding to the receptor, SARS- CoV induces CKII- mediated phosphorylation of ACE2 at Ser-787 that in-turn facilitate virus entry to host cells, followed by replication and activation of ACE2, initiates downstream signaling leading to lung fibrosis. Therefore, in this study, we have suggested post-translational modification (PTM) O-β-GlcNAcylation, and two compounds Chloroquine and 2-hydroxybenzohydrazine might share the common pathways to prevent the COVID-19 infection in human. The addition of O-β-GlcNAcylation at same or neighboring Ser/ Thr residues results in phosphorylation inhibition and a change in protein structural and functional confirmations. Thereby, using neural networking methods, we have identified Ser/ Thr residues in ACE2 that are potential sites for phosphorylation and / or O-β-GlcNAcylation. Molecular docking showed that UDP-GlcNAc has more binding affinity with Ser-787 than the phosphoryl group. Moreover, chloroquine and 2-hydroxybenzohydrazine also showed great potential to bind at Ser-787 that may result in inhibition of Ser-787 phosphorylation and downstream signaling. Furthermore, O-β-GlcNAcylation, chloroquine and 2-hydroxybenzohydrazine showed their high affinity at ACE2-SARS-CoV-2receptor binding domain that may prevent the entry of SARS-CoV-2 into human body. In conclusion, inhibition of human ACE2 phosphorylation at Ser-787 and ACE2-SARS-CoV-2 binding domain could be promising targets against SARS-CoV-2 infection.

scholarly journals Activation of Fusion by the SER Virus F Protein: a Low-pH-Dependent Paramyxovirus Entry Process

2003 ◽  
Vol 77 (11) ◽  
pp. 6520-6527 ◽  
Author(s):  
Shaguna Seth ◽  
Annelet Vincent ◽  
R. W. Compans
Keyword(s):  
Elevated Temperatures ◽  
Protein A ◽  
Syncytium Formation ◽  
Simian Virus ◽  
Low Ph ◽  
F Protein ◽  
Simian Virus 5 ◽  
Cytoplasmic Content ◽  
Ph Conditions ◽  
Ph Dependent

ABSTRACT SER virus, a paramyxovirus closely related to simian virus 5, induces no syncytium formation. The SER virus F protein has a long cytoplasmic tail (CT), and truncation or mutations of the CT result in enhanced syncytium formation (S. Seth, A. Vincent, and R. W. Compans, J. Virol. 77:167-178, 2003; S. Tong, M. Li, A. Vincent, R. W. Compans, E. Fritsch, R. Beier, C. Klenk, M. Ohuchi, and H.-D. Klenk, Virology 301:322-333, 2002). We hypothesized that the presence of the long CT serves to stabilize the metastable conformation of the F protein. We observed that the hemifusion, cytoplasmic content mixing, and syncytium formation ability of the wild-type SER virus F coexpressed with the SER virus hemagglutinin-neuraminidase (HN) protein was enhanced, both qualitatively and quantitatively, at elevated temperatures. We also observed enhanced hemifusion, content mixing, and syncytium formation in SER virus F- and HN-expressing cells at reduced pH conditions ranging between 4.8 and 6.2. We have obtained evidence that in contrast to other paramyxoviruses, entry of SER virus into cells occurs by a low-pH-dependent process, indicating that the conversion to the fusion-active state for SER virus F is triggered by exposure to reduced pH.

scholarly journals Functional Characterization of the Genomic Promoter of Borna Disease Virus (BDV): Implications of 3′-Terminal Sequence Heterogeneity for BDV Persistence

2005 ◽  
Vol 79 (10) ◽  
pp. 6544-6550 ◽  
Author(s):  
Debralee Rosario ◽  
Mar Perez ◽  
Juan Carlos de la Torre
Keyword(s):  
Disease Virus ◽  
Reverse Genetics ◽  
Functional Characterization ◽  
Borna Disease Virus ◽  
Virus Family ◽  
Sequence Heterogeneity ◽  
Enveloped Virus ◽  
A Genome ◽  
Polymerase I ◽  
Borna Disease

ABSTRACT Borna disease virus (BDV) is an enveloped virus with a genome organization characteristic of Mononegavirales. However, based on its unique features, BDV is considered the prototypic member of a new virus family, Bornaviridae, within the order Mononegavirales. We have described the establishment of a reverse genetics system for the rescue of BDV RNA analogues, or minigenomes, that is based on the use of polymerase I/polymerase II. Using this BDV minigenome rescue system, we have examined the functional implications of the reported sequence heterogeneity found at the 5′ and 3′ termini of the BDV genome and also defined the minimal BDV genomic promoter within the 3′-terminal 25 nucleotides. Our results suggest that the accumulation of RNA genome species containing truncations of one to three nucleotides at their 3′ termini may contribute to modulate BDV RNA replication and gene expression during long-term persistence.

scholarly journals Transmembrane 163 (TMEM163) protein effluxes zinc

2019 ◽  
Author(s):  
Vanessa B. Sanchez ◽  
Saima Ali ◽  
Adrian Escobar ◽  
Math P. Cuajungco
Keyword(s):  
Protein Function ◽  
Fluorescent Dyes ◽  
Phylogenetic Analyses ◽  
Site Directed Mutagenesis ◽  
Fluorescence Signal ◽  
Multiple Sequence ◽  
Protein Variant ◽  
Cellular Expression ◽  
Zinc Chelator ◽  
Zinc Levels

ABSTRACTRecent investigations of rodent Tmem163 suggest that it binds to and transports zinc as a dimer, and that alanine mutagenesis of its two species-conserved aspartate (D123A/D127A) residues proposed to bind zinc perturbs protein function. Direct corroboration, however, is lacking whether it is an influx or efflux transporter in cells. We hypothesized that human TMEM163 is a zinc effluxer based on its predicted protein characteristics. We used cultured human cell lines that either stably or transiently expressed TMEM163, and pre-loaded the cells with zinc to determine transport activity. We found that TMEM163-expressing cells exhibited significant reduction of intracellular zinc levels as evidenced by two zinc-specific fluorescent dyes and radionuclide zinc-65. The specificity of the fluorescence signal was confirmed upon treatment with TPEN, a high-affinity zinc chelator. Multiple sequence alignment and phylogenetic analyses showed that TMEM163 is related to distinct members of the cation diffusion facilitator (CDF) protein family. To further characterize the efflux function of TMEM163, we substituted alanine in two homologous aspartate residues (D124A/D128A) and performed site-directed mutagenesis of several conserved amino acid residues identified as non-synonymous single nucleotide polymorphism (S61R, S95C, S193P, and E286K). We found a significant reduction of zinc efflux upon cellular expression of D124A/D128A or E286K protein variant when compared with wild-type, suggesting that these particular amino acids are important for normal protein function. Taken together, our findings demonstrate that TMEM163 effluxes zinc and should now be designated ZNT11, as a new member of the mammalian CDF family of zinc efflux transporters.

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