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1.
Genomics ; 112(5): 3226-3237, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32540495

RESUMO

A global emergency due to the COVID-19 pandemic demands various studies related to genes and genomes of the SARS-CoV2. Among other important proteins, the role of accessory proteins are of immense importance in replication, regulation of infections of the coronavirus in the hosts. The largest accessory protein in the SARS-CoV2 genome is ORF3a which modulates the host response to the virus infection and consequently it plays an important role in pathogenesis. In this study, an attempt is made to decipher the conservation of nucleotides, dimers, codons and amino acids in the ORF3a genes across thirty-two genomes of Indian patients. ORF3a gene possesses single and double point mutations in Indian SARS-CoV2 genomes suggesting the change of SARS-CoV2's virulence property in Indian patients. We find that the parental origin of the ORF3a gene over the genomes of SARS-CoV2 and Pangolin-CoV is same from the phylogenetic analysis based on conservation of nucleotides and so on. This study highlights the accumulation of mutation on ORF3a in Indian SARS-CoV2 genomes which may provide the designing therapeutic approach against SARS-CoV2.


Assuntos
Betacoronavirus/genética , Sequência Conservada , Infecções por Coronavirus/virologia , Mutação , Pneumonia Viral/virologia , Proteínas Virais Reguladoras e Acessórias/genética , Animais , Sequência de Bases , Evolução Biológica , Quirópteros/virologia , Infecções por Coronavirus/veterinária , Eutérios/virologia , Genoma Viral , Genômica , Humanos , Índia , Pandemias , Filogenia , Proteínas Virais Reguladoras e Acessórias/química , Proteínas Estruturais Virais/química , Proteínas Estruturais Virais/genética
2.
Med Sci (Paris) ; 36(6-7): 633-641, 2020.
Artigo em Francês | MEDLINE | ID: mdl-32558641

RESUMO

Coronavirus is a large family of viruses that infect mammals and birds. Coronaviruses are known to cross barrier species and infect new ones. In the past twenty years, we witnessed the emergence of three different coronaviruses, the latest one being the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) responsible for the COVID-19 (covid disease 19) pandemic. Coronaviruses are enveloped virus with a long positive sense RNA genome. Like all viruses, they hijack the cellular machinery to replicate and produce new virions. There is no approved vaccine or specific antiviral molecule against coronaviruses but with the urgency to treat COVID-19, several candidate therapies are currently investigated.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Fenômenos Fisiológicos Virais , Animais , Betacoronavirus/classificação , Betacoronavirus/fisiologia , Betacoronavirus/ultraestrutura , Infecções por Coronavirus/tratamento farmacológico , Epidemias , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Vírus da SARS , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/virologia , Proteínas Estruturais Virais/química , Zoonoses/epidemiologia , Zoonoses/virologia
3.
Arch Virol ; 165(7): 1611-1620, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32405826

RESUMO

Infectious bursal disease virus (IBDV), which infects young chickens, is one of the most important pathogens that harm the poultry industry. Evaluation of the immune status of birds before and after vaccination is of great importance for controlling the disease caused by this virus. Therefore, the development of low-cost and easy-to-manufacture test systems for IBDV antibody detection remains an urgent issue. In this study, three expression systems (bacteria, yeast, and human cells) were used to produce recombinant VP3 protein of IBDV. VP3 is a group-specific antigen and hence may be a good candidate for use in diagnostic tests. Comparison of the antigenic properties of the obtained polypeptides showed that the titres of antibodies raised in chickens against bacteria- or human-cell-derived recombinant VP3 were high, whereas the antibody level against yeast-derived recombinant VP3 was low. The results of an enzyme-linked immunosorbent assay (ELISA) of sera from IBDV-infected chickens demonstrated that the recombinant VP3 produced in E. coli would be the best choice for use in test systems.


Assuntos
Infecções por Birnaviridae/veterinária , Vírus da Doença Infecciosa da Bursa/imunologia , Peptídeos/imunologia , Doenças das Aves Domésticas/virologia , Proteínas Estruturais Virais/imunologia , Animais , Anticorpos Antivirais/imunologia , Infecções por Birnaviridae/virologia , Galinhas , Ensaio de Imunoadsorção Enzimática , Mapeamento de Epitopos , Escherichia coli/genética , Escherichia coli/metabolismo , Vírus da Doença Infecciosa da Bursa/química , Vírus da Doença Infecciosa da Bursa/genética , Vírus da Doença Infecciosa da Bursa/isolamento & purificação , Peptídeos/química , Peptídeos/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Estruturais Virais/química , Proteínas Estruturais Virais/genética
4.
Acta Virol ; 64(1): 44-58, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32180418

RESUMO

Protein disulfide isomerase (PDI) is an enzyme that catalyzes disulfide bond reduction or formation and rearrangements of disulfide bridges, and also functions as a chaperone. During entry of some of the viruses PDI participates in thiol-disulfide exchange. Previous reports show that rotavirus entry is interfered by impermeant thiol/disulfide exchange inhibitors and antibodies against PDI. Our objective was to assess the interaction between PDI and triple-layered particles (TLPs) from rotavirus strains ECwt and RRV and from a human rotavirus isolate (HI) during the early steps of virus entry in a system of isolated small intestinal villi. Purified soluble PDI was incubated with either isolated intestinal villi or cell membrane-enriched fractions in the presence or absence of thiol/disulfide inhibitors such as bacitracin, DTNB or N- ethylmaleimide followed by the assessment of the PDI interactions with TLPs and rotavirus structural proteins in terms of their redox state changes. Soluble and membrane-bound PDI was found to interact with TLPs from all the rotaviruses assayed and also with the isolated structural proteins represented by the recombinant rVP5* (a tryptic cleavage product of VP4), rVP6 and the native VP7. PDI interaction with TLPs and rotavirus structural proteins was decreased by the presence of thiol/disulfide exchange inhibitors. Interactions of cell membrane-enriched fractions with TLPs produced rearrangements in the disulfide bridges of rotavirus structural proteins. We conclude that PDI interacts with rotavirus virions through redox reactions that could facilitate the rotavirus entry into the host cell. Keywords: cell surface PDI; thiol-disulfide exchange; rotavirus TLPs; virus entry; bacitracin; DTNB.


Assuntos
Dissulfetos/química , Mucosa Intestinal/virologia , Rotavirus/fisiologia , Compostos de Sulfidrila/química , Proteínas Estruturais Virais/química , Membrana Celular/virologia , Humanos , Técnicas In Vitro , Isomerases de Dissulfetos de Proteínas , Internalização do Vírus
5.
Proc Natl Acad Sci U S A ; 117(4): 2099-2107, 2020 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-31953264

RESUMO

Nonsegmented negative-stranded (NNS) RNA viruses, among them the virus that causes rabies (RABV), include many deadly human pathogens. The large polymerase (L) proteins of NNS RNA viruses carry all of the enzymatic functions required for viral messenger RNA (mRNA) transcription and replication: RNA polymerization, mRNA capping, and cap methylation. We describe here a complete structure of RABV L bound with its phosphoprotein cofactor (P), determined by electron cryo-microscopy at 3.3 Å resolution. The complex closely resembles the vesicular stomatitis virus (VSV) L-P, the one other known full-length NNS-RNA L-protein structure, with key local differences (e.g., in L-P interactions). Like the VSV L-P structure, the RABV complex analyzed here represents a preinitiation conformation. Comparison with the likely elongation state, seen in two structures of pneumovirus L-P complexes, suggests differences between priming/initiation and elongation complexes. Analysis of internal cavities within RABV L suggests distinct template and product entry and exit pathways during transcription and replication.


Assuntos
RNA Polimerases Dirigidas por DNA/química , RNA Polimerases Dirigidas por DNA/metabolismo , Chaperonas Moleculares/química , Vírus da Raiva/enzimologia , Proteínas Virais/química , Proteínas Virais/metabolismo , Proteínas Estruturais Virais/química , Microscopia Crioeletrônica , RNA Polimerases Dirigidas por DNA/genética , Regulação Viral da Expressão Gênica , Humanos , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Ligação Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Viral/genética , RNA Viral/metabolismo , Vírus da Raiva/química , Vírus da Raiva/genética , Vírus da Raiva/metabolismo , Transcrição Genética , Proteínas Virais/genética , Proteínas Estruturais Virais/genética , Proteínas Estruturais Virais/metabolismo
6.
Microb Pathog ; 128: 254-262, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30616000

RESUMO

Foot and Mouth disease (FMD) is economically devastating, highly contagious transboundry viral disease of livestock with 100% morbidity, rapid spread and severe production losses in animals. The FMDV has seven different serotypes. There is no vaccine that can protect animals from all serotypes. Hence, it is need of the day to develop a vaccine that protects animals from hetrologous challenge. In this study, we used immunoinformatics approach to find T and B-cell epitopes that will help to construct a universal vaccine for FMDV. For this purpose, first we constructed a consensus sequence for four structural proteins (VP1, VP2, VP3 and VP4) of aphthovirus for seven serotypes (A, O, C, Asia1, SAT1, SAT2 and SAT3). Various computational tools were used to perform multiple sequence alignment to identify the conserved regions, generation of consensus sequence through conserved regions, structures prediction and finally prediction of B and T cell epitopes. We predicted 5 B cell and 18 T cell epitopes. Finally a GPGPG spacer was used to join these epitopes to decrease binding affinity around the core binding regions. Hence, our study identified the epitopes which can be used to develop cross protective vaccines against all the fatal strains of Aphthovirus which can easily protect all the serotypes. Though, successful In vivo and In vitro studies are required to determine the genuine strength of our predicted epitopes against the fatal strains of Aphthovirus.


Assuntos
Antígenos Virais/imunologia , Aphthovirus/imunologia , Epitopos de Linfócito B/metabolismo , Epitopos de Linfócito T/imunologia , Proteínas Estruturais Virais/imunologia , Animais , Antígenos Virais/química , Simulação por Computador , Sequência Consenso , Epitopos/química , Epitopos/imunologia , Epitopos de Linfócito B/química , Epitopos de Linfócito T/química , Febre Aftosa/imunologia , Febre Aftosa/prevenção & controle , Vírus da Febre Aftosa/imunologia , Interações Hidrofóbicas e Hidrofílicas , Conformação Proteica , Alinhamento de Sequência , Sorogrupo , Proteínas Virais/química , Proteínas Virais/imunologia , Proteínas Estruturais Virais/química , Vacinas Virais/imunologia
7.
Biomol NMR Assign ; 13(1): 5-8, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30238347

RESUMO

The C-terminal domain of the P protein of rabies virus is a multifunctional domain that interacts with both viral and host cell proteins. Here we report the 1H, 13C and 15N chemical shift assignments of this domain from P protein of the Nishigahara strain of rabies virus, a pathogenic laboratory strain well established for studies of virulence functions of rabies virus proteins, including P protein. The data and secondary structure analysis are in good agreement with the reported predominantly helical structure of the same domain from the CVS strain of rabies solved by crystallography. These assignments will enable future solution studies of the interactions of the P protein with viral and host proteins, and the effects of post-translational modifications.


Assuntos
Ressonância Magnética Nuclear Biomolecular , Fosfoproteínas/química , Vírus da Raiva/química , Proteínas Estruturais Virais/química , Isótopos de Carbono , Chaperonas Moleculares , Isótopos de Nitrogênio , Domínios Proteicos , Estrutura Secundária de Proteína , Prótons
8.
J Virol ; 93(3)2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30429342

RESUMO

Ubiquitination is critical for several cellular physical processes. However, ubiquitin modification in virus replication is poorly understood. Therefore, the present study aimed to determine the presence and effect of ubiquitination on polymerase activity of viral protein 1 (VP1) of avibirnavirus. We report that the replication of avibirnavirus is regulated by ubiquitination of its VP1 protein, the RNA-dependent RNA polymerase of infectious bursal disease virus (IBDV). In vivo detection revealed the ubiquitination of VP1 protein in IBDV-infected target organs and different cells but not in purified IBDV particles. Further analysis of ubiquitination confirms that VP1 is modified by K63-linked ubiquitin chain. Point mutation screening showed that the ubiquitination site of VP1 was at the K751 residue in the C terminus. The K751 ubiquitination is independent of VP1's interaction with VP3 and eukaryotic initiation factor 4A II. Polymerase activity assays indicated that the K751 ubiquitination at the C terminus of VP1 enhanced its polymerase activity. The K751-to-R mutation of VP1 protein did not block the rescue of IBDV but decreased the replication ability of IBDV. Our data demonstrate that the ubiquitination of VP1 is crucial to regulate its polymerase activity and IBDV replication.IMPORTANCE Avibirnavirus protein VP1, the RNA-dependent RNA polymerase, is responsible for IBDV genome replication, gene expression, and assembly. However, little is known about its chemical modification relating to its polymerase activity. In this study, we revealed the molecular mechanism of ubiquitin modification of VP1 via a K63-linked ubiquitin chain during infection. Lysine (K) residue 751 at the C terminus of VP1 is the target site for ubiquitin, and its ubiquitination is independent of VP1's interaction with VP3 and eukaryotic initiation factor 4A II. The K751 ubiquitination promotes the polymerase activity of VP1 and unubiquitinated VP1 mutant IBDV significantly impairs virus replication. We conclude that VP1 is the ubiquitin-modified protein and reveal the mechanism by which VP1 promotes avibirnavirus replication.


Assuntos
Avibirnavirus/fisiologia , Infecções por Birnaviridae/virologia , Vírus da Doença Infecciosa da Bursa/fisiologia , RNA Replicase/metabolismo , Ubiquitinação , Proteínas Estruturais Virais/metabolismo , Replicação Viral , Animais , Avibirnavirus/classificação , Infecções por Birnaviridae/enzimologia , Células Cultivadas , Galinhas/virologia , Fibroblastos/metabolismo , Fibroblastos/virologia , Células HEK293 , Humanos , RNA Replicase/química , Ubiquitina/metabolismo , Proteínas Estruturais Virais/química
9.
mBio ; 9(6)2018 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-30425144

RESUMO

Human respiratory syncytial virus (HRSV) is a negative-stranded RNA virus that causes a globally prevalent respiratory infection, which can cause life-threatening illness, particularly in the young, elderly, and immunocompromised. HRSV multiplication depends on replication and transcription of the HRSV genes by the virus-encoded RNA-dependent RNA polymerase (RdRp). For replication, this complex comprises the phosphoprotein (P) and the large protein (L), whereas for transcription, the M2-1 protein is also required. M2-1 is recruited to the RdRp by interaction with P and also interacts with RNA at overlapping binding sites on the M2-1 surface, such that binding of these partners is mutually exclusive. The molecular basis for the transcriptional requirement of M2-1 is unclear, as is the consequence of competition between P and RNA for M2-1 binding, which is likely a critical step in the transcription mechanism. Here, we report the crystal structure at 2.4 Å of M2-1 bound to the P interaction domain, which comprises P residues 90 to 110. The P90-110 peptide is alpha helical, and its position on the surface of M2-1 defines the orientation of the three transcriptase components within the complex. The M2-1/P interface includes ionic, hydrophobic, and hydrogen bond interactions, and the critical contribution of these contacts to complex formation was assessed using a minigenome assay. The affinity of M2-1 for RNA and P ligands was quantified using fluorescence anisotropy, which showed high-affinity RNAs could outcompete P. This has important implications for the mechanism of transcription, particularly the events surrounding transcription termination and synthesis of poly(A) sequences.IMPORTANCE Human respiratory syncytial virus (HRSV) is a leading cause of respiratory illness, particularly in the young, elderly, and immunocompromised, and has also been linked to the development of asthma. HRSV replication depends on P and L, whereas transcription also requires M2-1. M2-1 interacts with P and RNA at overlapping binding sites; while these interactions are necessary for transcriptional activity, the mechanism of M2-1 action is unclear. To better understand HRSV transcription, we solved the crystal structure of M2-1 in complex with the minimal P interaction domain, revealing molecular details of the M2-1/P interface and defining the orientation of M2-1 within the tripartite complex. The M2-1/P interaction is relatively weak, suggesting high-affinity RNAs may displace M2-1 from the complex, providing the basis for a new model describing the role of M2-1 in transcription. Recently, the small molecules quercetin and cyclopamine have been used to validate M2-1 as a drug target.


Assuntos
Fosfoproteínas/química , Vírus Sincicial Respiratório Humano/química , Proteínas Virais/química , Proteínas Estruturais Virais/química , Sítios de Ligação , Cristalização , Humanos , Ligação Proteica , Vírus Sincicial Respiratório Humano/genética , Transcrição Genética
10.
PLoS Pathog ; 14(10): e1007383, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30339712

RESUMO

Rabbit hemorrhagic disease virus (RHDV) is an important member of the Caliciviridae family and a highly lethal pathogen in rabbits. Although the cell receptor of RHDV has been identified, the mechanism underlying RHDV internalization remains unknown. In this study, the entry and post-internalization of RHDV into host cells were investigated using several biochemical inhibitors and RNA interference. Our data demonstrate that rabbit nucleolin (NCL) plays a key role in RHDV internalization. Further study revealed that NCL specifically interacts with the RHDV capsid protein (VP60) through its N-terminal residues (aa 285-318), and the exact position of the VP60 protein for the interaction with NCL is located in a highly conserved region (472Asp-Val-Asn474; DVN motif). Following competitive blocking of the interaction between NCL and VP60 with an artificial DVN peptide (RRTGDVNAAAGSTNGTQ), the internalization efficiency of the virus was markedly reduced. Moreover, NCL also interacts with the C-terminal residues of clathrin light chain A, which is an important component in clathrin-dependent endocytosis. In addition, the results of animal experiments also demonstrated that artificial DVN peptides protected most rabbits from RHDV infection. These findings demonstrate that NCL is involved in RHDV internalization through clathrin-dependent endocytosis.


Assuntos
Infecções por Caliciviridae/virologia , Clatrina/metabolismo , Endocitose , Vírus da Doença Hemorrágica de Coelhos/fisiologia , Fosfoproteínas/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas Estruturais Virais/metabolismo , Montagem de Vírus , Animais , Masculino , Camundongos , Fosfoproteínas/química , Fosfoproteínas/genética , Conformação Proteica , Proteínas de Ligação a RNA/química , Proteínas de Ligação a RNA/genética , Coelhos , Proteínas Estruturais Virais/química , Proteínas Estruturais Virais/genética , Internalização do Vírus
11.
Appl Microbiol Biotechnol ; 102(22): 9707-9718, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30187100

RESUMO

The protrusion (P) domain of the major structural protein VP1 of norovirus (NoV) is critical for the host's immune response and receptor binding. Most heterologous P domains expressed in Escherichia coli or Komagataella pastoris (formally known as Pichia pastoris) form P particles consisting of 24 P monomers formed through intermolecular contact in the P regions and an end-linked cysteine tag. The small P particle is only found in P domains with terminal modifications. In this study, the NoV P domain of the most predominant NoV strain GII.4 isolated from Taiwan was expressed in K. pastoris. A high yield of NoV P was obtained using the high-cell density fermentation process in K. pastoris. A large amount of the small P particles and the trimer and dimer complexes formed by 12, 6, and 2 P monomers were observed in both the expression of the NoV P-His and P containing cysteine tag at the N-terminus. Dynamic light scattering and transmission electron microscopy analysis of the purified NoV P-His and P revealed that most of these small P particles are triangle-, square-, and ring-shaped with a diameter of 14-15 nm. The binding ability of purified NoV P-His and P to human histo-blood group antigen was confirmed by a saliva-binding assay. Without terminal modification, small P particles were formed in our study. The amino acid sequence analysis showed only four different amino acids (residue 84, 119, 136, and 313) between the P domain in this study and other investigated GII.4 strains suggesting that these amino acids might play an important role in the P particle formation. The small P particles formed by the Taiwan-native norovirus P domain overexpressed in K. pastoris may provide further information for morphogenesis studies and vaccine development.


Assuntos
Norovirus/genética , Saccharomycetales/metabolismo , Proteínas Estruturais Virais/química , Proteínas Estruturais Virais/genética , Motivos de Aminoácidos , Expressão Gênica , Humanos , Norovirus/química , Norovirus/metabolismo , Domínios Proteicos , Saccharomycetales/genética , Taiwan , Proteínas Estruturais Virais/metabolismo
12.
Sheng Wu Gong Cheng Xue Bao ; 34(9): 1432-1441, 2018 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-30255677

RESUMO

Newcastle disease virus is paramyxoviridae, Avian mumps virus genus type I, and infects more than 250 species of birds, causing huge losses on poultry farming worldwide. Numerous experiments have demonstrated that Newcastle disease virus has oncolytic activity on tumor cells and can selectively replicate in cancer cells. Thus, Newcastle disease virus is a potential therapeutic agent for cancer treatment. Some human clinical trials achieved good results. In this review, we summarized research progress of the relationship between the structural protein of Newcastle disease virus and virulence, anti-tumor and autophagy of Newcastle disease.


Assuntos
Neoplasias/terapia , Vírus da Doença de Newcastle , Terapia Viral Oncolítica , Proteínas Estruturais Virais/química , Animais , Autofagia , Aves , Humanos
13.
Annu Rev Virol ; 5(1): 185-207, 2018 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-30265634

RESUMO

Flaviviruses are arthropod-borne RNA viruses that are a significant threat to global health due to their widespread distribution, ability to cause severe disease in humans, and capacity for explosive spread following introduction into new regions. Members of this genus include dengue, tick-borne encephalitis, yellow fever, and Zika viruses. Vaccination has been a highly successful means to control flaviviruses, and neutralizing antibodies are an important component of a protective immune response. High-resolution structures of flavivirus structural proteins and virions, alone and in complex with antibodies, provide a detailed understanding of viral fusion mechanisms and virus-antibody interactions. However, mounting evidence suggests these structures provide only a snapshot of an otherwise structurally dynamic virus particle. The contribution of the structural ensemble arising from viral breathing to the biology, antigenicity, and immunity of flaviviruses is discussed, including implications for the development and evaluation of flavivirus vaccines.


Assuntos
Flavivirus/imunologia , Flavivirus/ultraestrutura , Proteínas Estruturais Virais/química , Proteínas Estruturais Virais/imunologia , Vacinas Virais/imunologia , Vírion/imunologia , Vírion/ultraestrutura , Infecções por Flavivirus/prevenção & controle , Humanos , Vacinas Virais/isolamento & purificação
14.
J Biol Chem ; 293(41): 15827-15839, 2018 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-30166339

RESUMO

In all herpesviruses, the space between the capsid shell and the lipid envelope is occupied by the unique tegument layer composed of proteins that, in addition to structural roles, play many other roles in the viral replication. UL37 is a highly conserved tegument protein that has activities ranging from virion morphogenesis to directional capsid trafficking to manipulation of the host innate immune response and binds multiple partners. The N-terminal half of UL37 (UL37N) has a compact bean-shaped α-helical structure that contains a surface region essential for neuroinvasion. However, no biochemical or structural information is currently available for the C-terminal half of UL37 (UL37C) that mediates most of its interactions with multiple binding partners. Here, we show that the C-terminal half of UL37 from pseudorabies virus UL37C is a conformationally flexible monomer composed of an elongated folded core and an unstructured C-terminal tail. This elongated structure, along with that of its binding partner UL36, explains the nature of filamentous tegument structures bridging the capsid and the envelope. We propose that the dynamic nature of UL37 underlies its ability to perform diverse roles during viral replication.


Assuntos
Proteínas Estruturais Virais/química , Herpesvirus Suídeo 1/química , Modelos Moleculares , Conformação Proteica em alfa-Hélice , Domínios Proteicos , Espalhamento a Baixo Ângulo , Temperatura de Transição , Difração de Raios X
15.
Eur J Med Chem ; 156: 444-460, 2018 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-30015077

RESUMO

Continuously increasing number of reports of Zika virus (ZIKV) infections and associated severe clinical manifestations, including autoimmune abnormalities and neurological disorders such as neonatal microcephaly and Guillain-Barré syndrome have created alarming situation in various countries. To date, no specific antiviral therapy or vaccine is available against ZIKV. This review provides a comprehensive insight into the potential therapeutic targets and describes viral epitopes of broadly neutralizing antibodies (bNAbs) in vaccine design perspective. Interactions between ZIKV envelope glycoprotein E and cellular receptors mediate the viral fusion and entry to the target cell. Blocking these interactions by targeting cellular receptors or viral structural proteins mediating these interactions or viral surface glycans can inhibit viral entry to the cell. Similarly, different non-structural proteins of ZIKV and un-translated regions (UTRs) of its RNA play essential roles in viral replication cycle and potentiate for therapeutic interventions. Structure based vaccine design requires identity and structural description of the epitopes of bNAbs. We have described different conserved bNAb epitopes present in the ZIKV envelope as potential targets for structure based vaccine design. This review also highlights successes, unanswered questions and future perspectives in relation to therapeutic and vaccine development against ZIKV.


Assuntos
Vacinas Virais/imunologia , Infecção por Zika virus/prevenção & controle , Zika virus/imunologia , Animais , Anticorpos Neutralizantes/química , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/farmacologia , Epitopos/química , Epitopos/imunologia , Humanos , Modelos Moleculares , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/imunologia , Proteínas Estruturais Virais/química , Proteínas Estruturais Virais/imunologia , Vacinas Virais/química , Vacinas Virais/farmacologia , Internalização do Vírus , Zika virus/química , Zika virus/fisiologia , Infecção por Zika virus/imunologia
16.
Int J Mol Sci ; 19(6)2018 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-29914091

RESUMO

Bacteriophages, which are tremendously important to the ecology and evolution of bacteria, play a key role in the development of genetic engineering. Bacteriophage virion proteins are essential materials of the infectious viral particles and in charge of several of biological functions. The correct identification of bacteriophage virion proteins is of great importance for understanding both life at the molecular level and genetic evolution. However, few computational methods are available for identifying bacteriophage virion proteins. In this paper, we proposed a new method to predict bacteriophage virion proteins using a Multinomial Naïve Bayes classification model based on discrete feature generated from the g-gap feature tree. The accuracy of the proposed model reaches 98.37% with MCC of 96.27% in 10-fold cross-validation. This result suggests that the proposed method can be a useful approach in identifying bacteriophage virion proteins from sequence information. For the convenience of experimental scientists, a web server (PhagePred) that implements the proposed predictor is available, which can be freely accessed on the Internet.


Assuntos
Bacteriófagos/química , Análise de Sequência de Proteína/métodos , Proteínas Estruturais Virais/química , Teorema de Bayes , Análise de Sequência de Proteína/normas , Software
17.
Methods Mol Biol ; 1776: 471-485, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29869261

RESUMO

Potyviruses are plant viruses with elongated, flexuous virions amenable to modifications in the only viral structural protein, the coat protein (CP). Out of the several theoretically possible modifications to the CP, the one most exploited for peptide presentation is the genetic fusion of the peptide-to-be-expressed, to the CP N-terminus. Successful high-level expression of the modified CP has been achieved this way. The purified recombinant viral particles incorporate most, if not all, the properties of the expressed peptides. For many purposes, the recombinant virus particles present in extracts of infected plants should be purified for further use. Procedures for carrying out the whole process, from cloning to purification are described in the chapter.


Assuntos
Peptídeos/genética , Doenças das Plantas/virologia , Vírus de Plantas/genética , Potyvirus/genética , Capsídeo/química , Peptídeos/química , Doenças das Plantas/genética , Vírus de Plantas/patogenicidade , Proteínas Estruturais Virais/química , Proteínas Estruturais Virais/genética , Vírion/genética , Vírion/crescimento & desenvolvimento
18.
Adv Exp Med Biol ; 1045: 227-249, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29896670

RESUMO

Betaherpesvirus possesses a large genome DNA with a lot of open reading frames, indicating abundance in the variety of viral protein factors. Because the complicated pathogenicity of herpesvirus reflects the combined functions of these factors, analyses of individual proteins are the fundamental steps to comprehensively understand about the viral life cycle and the pathogenicity. In this chapter, structural aspects of the betaherpesvirus-encoded proteins are introduced. Betaherpesvirus-encoded proteins of which structural information is available were summarized and subcategorized into capsid proteins, tegument proteins, nuclear egress complex proteins, envelope glycoproteins, enzymes, and immune-modulating factors. Structure of capsid proteins are analyzed in capsid by electron cryomicroscopy at quasi-atomic resolution. Structural information of teguments is limited, but a recent crystallographic analysis of an essential tegument protein of human herpesvirus 6B is introduced. As for the envelope glycoproteins, crystallographic analysis of glycoprotein gB has been done, revealing the fine-tuned structure and the distribution of its antigenic domains. gH/gL structure of betaherpesvirus is not available yet, but the overall shape and the spatial arrangement of the accessory proteins are analyzed by electron microscopy. Nuclear egress complex was analyzed from the structural perspective in 2015, with the structural analysis of cytomegalovirus UL50/UL53. The category "enzymes" includes the viral protease, DNA polymerase and terminase for which crystallographic analyses have been done. The immune-modulating factors are viral ligands or receptors for immune regulating factors of host immune cells, and their communications with host immune molecules are demonstrated in the aspect of molecular structure.


Assuntos
Betaherpesvirinae/metabolismo , Infecções por Herpesviridae/virologia , Proteínas Estruturais Virais/química , Proteínas Estruturais Virais/metabolismo , Animais , Betaherpesvirinae/química , Betaherpesvirinae/genética , Núcleo Celular/virologia , Humanos , Proteínas Estruturais Virais/genética , Liberação de Vírus
19.
Sci Rep ; 8(1): 5822, 2018 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-29643398

RESUMO

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus. The outbreak of CHIKV infection has been seen in many tropical and subtropical regions of the biosphere. Current reports evidenced that after outbreaks in 2005-06, the fitness of this virus propagating in Aedes albopictus enhanced due to the epistatic mutational changes in its envelope protein. In our study, we evaluated the prevalence of intrinsically disordered proteins (IDPs) and IDP regions (IDPRs) in CHIKV proteome. IDPs/IDPRs are known as members of a 'Dark Proteome' that defined as a set of polypeptide segments or whole protein without unique three-dimensional structure within the cellular milieu but with significant biological functions, such as cell cycle regulation, control of signaling pathways, and maintenance of viral proteomes. However, the intrinsically disordered aspects of CHIKV proteome and roles of IDPs/IDPRs in the pathogenic mechanism of this important virus have not been evaluated as of yet. There are no existing reports on the analysis of intrinsic disorder status of CHIKV. To fulfil this goal, we have analyzed the abundance and functionality of IDPs/IDPRs in CHIKV proteins, involved in the replication and maturation. It is likely that these IDPs/IDPRs can serve as novel targets for disorder based drug design.


Assuntos
Febre de Chikungunya/virologia , Vírus Chikungunya/química , Proteínas Intrinsicamente Desordenadas/análise , Proteoma/análise , Aedes/virologia , Animais , Febre de Chikungunya/patologia , Vírus Chikungunya/genética , Vírus Chikungunya/patogenicidade , Cristalografia por Raios X , Humanos , Proteínas Intrinsicamente Desordenadas/química , Proteínas Intrinsicamente Desordenadas/genética , Mutação , Estrutura Terciária de Proteína , Proteoma/química , Proteoma/genética , Proteômica/métodos , Proteínas não Estruturais Virais/análise , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/genética , Proteínas Estruturais Virais/análise , Proteínas Estruturais Virais/química , Proteínas Estruturais Virais/genética
20.
Acta Virol ; 62(1): 86-97, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29521107

RESUMO

Infectious bursal disease virus isolates obtained from southern parts of India were subjected to comparative sequencing and phylogenetic analysis of 743bp hypervariable region of VP2. The sequence analysis showed that among eight isolates, only HY12 showed the characteristic conserved amino acid residues at 256I, 294I, and 299S of vvIBDV. Six isolates BGE14, PY12, NKL14, VCN14, RPM14 and EDE14 had conserved amino acid residues at 256I and 299S, whereas at residue 294, isoleucine was substituted by valine. The remaining isolate MB11 had leucine at residue 294 and asparagine at residue 299 similar to classical strain 52/70. The serine-rich heptapeptide sequence SWSASGS adjacent to the second hydrophilic region was conserved in all seven Indian IBDV isolates except isolate MB11. Conservation of this sequence was earlier reported to be an indication of a virus isolate being pathogenic in nature. The reported heptapeptide sequence of the classical strain is 'SWSARGS'. In the present study, 'SWSARGS' heptapeptide sequence was observed in MB11 isolate. The pathogenicity trials conducted with these isolates further confirmed the genome analysis in classification. This study further reveals that the circulating IBDV strains in India could be diverse in nature.


Assuntos
Infecções por Birnaviridae/veterinária , Galinhas , Vírus da Doença Infecciosa da Bursa/genética , Doenças das Aves Domésticas/virologia , Proteínas Estruturais Virais/genética , Animais , Infecções por Birnaviridae/epidemiologia , Infecções por Birnaviridae/virologia , Índia/epidemiologia , Filogenia , Doenças das Aves Domésticas/epidemiologia , Proteínas Estruturais Virais/química
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