Orchid Fleck Virus Structural Proteins N and P Form Intranuclear Viroplasm-Like Structures in the Absence of Viral Infection

ABSTRACT White spot syndrome virus (WSSV) is a virulent pathogen known to infect various crustaceans. It has bacilliform morphology with a tail-like appendage at one end. The envelope consists of four major proteins. Envelope structural proteins play a crucial role in viral infection and are believed to be the first molecules to interact with the host. Here, we report the localization and crystal structure of major envelope proteins VP26 and VP28 from WSSV at resolutions of 2.2 and 2.0 Å, respectively. These two proteins alone account for approximately 60% of the envelope, and their structures represent the first two structural envelope proteins of WSSV. Structural comparisons among VP26, VP28, and other viral proteins reveal an evolutionary relationship between WSSV envelope proteins and structural proteins from other viruses. Both proteins adopt β-barrel architecture with a protruding N-terminal region. We have investigated the localization of VP26 and VP28 using immunoelectron microscopy. This study suggests that VP26 and VP28 are located on the outer surface of the virus and are observed as a surface protrusion in the WSSV envelope, and this is the first convincing observation for VP26. Based on our studies combined with the literature, we speculate that the predicted N-terminal transmembrane region of VP26 and VP28 may anchor on the viral envelope membrane, making the core β-barrel protrude outside the envelope, possibly to interact with the host receptor or to fuse with the host cell membrane for effective transfer of the viral infection. Furthermore, it is tempting to extend this host interaction mode to other structural viral proteins of similar structures. Our finding has the potential to extend further toward drug and vaccine development against WSSV.

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Corrigendum to “The structural proteins of epidemic and historical strains of Zika virus differ in their ability to initiate viral infection in human host cells” [Virology 516 (2018) 265–273]

Virology ◽

10.1016/j.virol.2018.11.006 ◽

2019 ◽

Vol 526 ◽

pp. 233

Author(s):

Sandra Bos ◽

Wildriss Viranaicken ◽

Jonathan Turpin ◽

Chaker El-Kalamouni ◽

Marjolaine Roche ◽

...

Keyword(s):

Viral Infection ◽

Zika Virus ◽

Host Cells ◽

Structural Proteins ◽

Human Host

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Penaeidins are a novel family of antiviral effectors against WSSV in shrimp

10.1101/467571 ◽

2018 ◽

Author(s):

Bang Xiao ◽

Qihui Fu ◽

Shengwen Niu ◽

Haoyang Li ◽

Kai Lǚ ◽

...

Keyword(s):

Viral Infection ◽

Signaling Pathways ◽

Outer Surface ◽

Phagocytic Activity ◽

White Spot Syndrome Virus ◽

Antiviral Immunity ◽

White Spot ◽

Structural Proteins ◽

First Report ◽

White Spot Syndrome

AbstractPenaeidins are members of a family of key effectors with broad anti-bacterial activities in penaeid shrimp. However, the function of penaeidins in antiviral immunity is rarely reported and remains largely unknown. Herein, we uncovered that penaeidins are a novel family of antiviral effectors against white spot syndrome virus (WSSV). Firstly, RNAi in vivo mediated knockdown of each penaeidin from four identified penaeidins from Litopenaeus vannamei resulted in elevated viral loads and rendered shrimp more susceptible to WSSV, whilst the phenotype of survival rate in penaeidin-silenced shrimp can be rescued via the injection of recombinant penaeidin proteins. Moreover, pull-down assays demonstrated the conserved PEN domain of penaeidin was able to interact with WSSV structural proteins. Furthermore, we observed that colloidal gold-labeled penaeidins were located on the outer surface of the WSSV virion. By infection-blocking assay, we observed that hemocytes had lower viral infection rates in the group of WSSV preincubated with penaeidins than those of control group. Phagocytic activity analysis further showed that penaeidins were able to inhibit phagocytic activity of hemocytes against WSSV Taken together, these results suggest that penaeidins specifically binds to WSSV virion by interacting with its structural proteins, thus preventing viral infection that confers host against WSSV. In addition, dual-luciferase assay and EMSA assay demonstrated that penaeidins were regulated by Dorsal and Relish, two transcription factors of the canonical Toll and IMD pathway, respectively. To our best knowledge, this is the first report on uncovering the antiviral function of penaeidins in the innate immune system of shrimp.ImportancesWhite spot syndrome, caused by white spot syndrome virus (WSSV), is the most serious disease in shrimp aquaculture, which has long been a scourge of cultured shrimp industry. Herein, we provided some substantial evidences to indicate that penaeidins are a novel family of effectors with antiviral activity against WSSV in shrimp. Penaeidins such as BigPEN, PEN2 and PEN3 were able to interact with the outer surface of WSSV virion via binding to viral structural proteins, and thus preventing viral entry host cells. In addition, we demonstrated that the Toll and IMD signaling pathways can regulate the transcriptional expression of penaeidins, which may suggest an important role of the conserved innate signaling pathways in antiviral immunity. This is the first report of the antiviral mechanism of penaeidins in shrimp, which may provide some new insights into strategies to control WSSV infection in shrimp farms.

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Advances in MERS-CoV Vaccines and Therapeutics Based on the Receptor-Binding Domain

Viruses ◽

10.3390/v11010060 ◽

2019 ◽

Vol 11 (1) ◽

pp. 60 ◽

Cited By ~ 48

Author(s):

Yusen Zhou ◽

Yang Yang ◽

Jingwei Huang ◽

Shibo Jiang ◽

Lanying Du

Keyword(s):

Middle East ◽

Viral Infection ◽

Receptor Binding ◽

Infectious Virus ◽

Binding Domain ◽

Structural Proteins ◽

Receptor Binding Domain ◽

Therapeutic Antibodies ◽

S Protein ◽

Important Target

Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) is an infectious virus that was first reported in 2012. The MERS-CoV genome encodes four major structural proteins, among which the spike (S) protein has a key role in viral infection and pathogenesis. The receptor-binding domain (RBD) of the S protein contains a critical neutralizing domain and is an important target for development of MERS vaccines and therapeutics. In this review, we describe the relevant features of the MERS-CoV S-protein RBD, summarize recent advances in the development of MERS-CoV RBD-based vaccines and therapeutic antibodies, and illustrate potential challenges and strategies to further improve their efficacy.

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EXPRESSION OF SINGLE-CHAIN VARIABLE FRAGMENTS AGAINST STRUCTURAL AND NON-STRUCTURAL PROTEINS OF PLUM POX VIRUS IN TRANSGENIC NICOTIANA BENTHAMIANA PLANTS TO INTERFERE WITH VIRAL INFECTION

Acta Horticulturae ◽

10.17660/actahortic.2004.657.54 ◽

2004 ◽

pp. 341-347 ◽

Cited By ~ 2

Author(s):

M. Gil ◽

O. Esteban ◽

M.C. Martínez ◽

M.T. Gorris ◽

L. Peña ◽

...

Keyword(s):

Viral Infection ◽

Nicotiana Benthamiana ◽

Structural Proteins ◽

Plum Pox Virus ◽

Single Chain ◽

Single Chain Variable Fragments

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Roles of African swine fever virus structural proteins in viral infection

Journal of Veterinary Research ◽

10.1515/jvetres-2017-0017 ◽

2017 ◽

Vol 61 (2) ◽

pp. 135-143 ◽

Cited By ~ 6

Author(s):

Ning Jia ◽

Yunwen Ou ◽

Zygmunt Pejsak ◽

Yongguang Zhang ◽

Jie Zhang

Keyword(s):

Viral Infection ◽

African Swine Fever Virus ◽

Control Strategies ◽

African Swine Fever ◽

Fever Virus ◽

Open Reading Frames ◽

Structural Proteins ◽

Domestic Pigs ◽

Virus Particles ◽

Double Stranded Dna

AbstractAfrican swine fever virus (ASFV) is a large, double-stranded DNA virus and the sole member of the Asfarviridae family. ASFV infects domestic pigs, wild boars, warthogs, and bush pigs, as well as soft ticks (Ornithodoros erraticus), which likely act as a vector. The major target is swine monocyte-macrophage cells. The virus can cause high fever, haemorrhagic lesions, cyanosis, anorexia, and even fatalities in domestic pigs. Currently, there is no vaccine and effective disease control strategies against its spread are culling infected pigs and maintaining high biosecurity standards. African swine fever (ASF) spread to Europe from Africa in the middle of the 20th century, and later also to South America and the Caribbean. Since then, ASF has spread more widely and thus is still a great challenge for swine breeding. The genome of ASFV ranges in length from about 170 to 193 kbp depending on the isolate and contains between 150 and 167 open reading frames (ORFs). The ASFV genome encodes 150 to 200 proteins, around 50 of them structural. The roles of virus structural proteins in viral infection have been described. These proteins, such as pp220, pp62, p72, p54, p30, and CD2v, serve as the major component of virus particles and have roles in attachment, entry, and replication. All studies on ASFV proteins lay a good foundation upon which to clarify the infection mechanism and develop vaccines and diagnosis methods. In this paper, the roles of ASFV structural proteins in viral infection are reviewed.

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Identification and characterization of structural proteins of orchid fleck virus

Archives of Virology ◽

10.1007/s00705-008-0268-6 ◽

2008 ◽

Vol 154 (1) ◽

pp. 37-45 ◽

Cited By ~ 18

Author(s):

Hideki Kondo ◽

Takanori Maeda ◽

Tetsuo Tamada

Keyword(s):

Structural Proteins ◽

Orchid Fleck Virus ◽

Identification And Characterization

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A Dengue Virus Serotype 1 mRNA-LNP Vaccine Elicits Protective Immune Responses

Journal of Virology ◽

10.1128/jvi.02482-20 ◽

2021 ◽

Author(s):

Clayton J. Wollner ◽

Michelle Richner ◽

Mariah A. Hassert ◽

Amelia K. Pinto ◽

James D. Brien ◽

...

Keyword(s):

Immune Responses ◽

Dengue Virus ◽

Viral Infection ◽

Neutralizing Antibody ◽

Viral Disease ◽

Structural Proteins ◽

Severe Dengue ◽

Antibody Dependent Enhancement ◽

Virus Serotype ◽

Serotype 1

Dengue virus (DENV) is the most common vector-borne viral disease with nearly 400 million worldwide infections each year concentrated in the tropical and subtropical regions of the world. Severe dengue complications are often associated with a secondary heterotypic infection of one of the four circulating serotypes. In this scenario, humoral immune responses targeting cross-reactive, poorly-neutralizing epitopes can lead to increased infectivity of susceptible cells via antibody-dependent enhancement (ADE). In this way, antibodies produced in response to infection or vaccination are capable of contributing to enhanced disease in subsequent infections. Currently, there are no available therapeutics to combat DENV disease, and there is an urgent need for a safe and efficacious vaccine. Here, we developed a nucleotide-modified mRNA vaccine encoding for the membrane and envelope structural proteins from DENV serotype 1 encapsulated into lipid nanoparticles (prM/E mRNA-LNP). Vaccination of mice elicited robust antiviral immune responses comparable to viral infection with high levels of neutralizing antibody titers and antiviral CD4+ and CD8+ T cells. Immunocompromised AG129 mice vaccinated with the prM/E mRNA-LNP vaccine were protected from a lethal DENV challenge. Vaccination with either a wild-type vaccine, or a vaccine with mutations in the immunodominant fusion-loop epitope, elicited equivalent humoral and cell mediated immune responses. Neutralizing antibodies elicited by the vaccine were sufficient to protect against a lethal challenge. Both vaccine constructs demonstrated serotype specific immunity with minimal serum cross-reactivity and reduced ADE compared to a live DENV1 viral infection. IMPORTANCE With 400 million worldwide infections each year, dengue is the most common vector-born viral disease. 40% of the world's population is at risk with dengue experiencing consistent geographic spread over the years. With no therapeutics available and vaccines performing sub optimally, the need for an effective dengue vaccine is urgent. Here we develop and characterize a novel mRNA vaccine encoding for the dengue serotype 1 envelope and premembrane structural proteins that is delivered via a lipid nanoparticle. Our DENV1 prM/E mRNA-LNP vaccine induces neutralizing antibody and cellular immune responses in immunocompetent mice and protects an immunocompromised mouse from a lethal DENV challenge. Existing antibodies against dengue can enhance subsequent infections via antibody-dependent enhancement. Importantly our vaccine only induced serotype specific immune responses and did not induce ADE.

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A mRNA-LNP vaccine against Dengue Virus elicits robust, serotype-specific immunity

10.1101/2021.01.05.425517 ◽

2021 ◽

Author(s):

Clayton J. Wollner ◽

Michelle Richner ◽

Mariah A. Hassert ◽

Amelia K. Pinto ◽

James D. Brien ◽

...

Keyword(s):

Immune Responses ◽

Dengue Virus ◽

Viral Infection ◽

Neutralizing Antibody ◽

Viral Disease ◽

Structural Proteins ◽

Severe Dengue ◽

Antibody Dependent Enhancement ◽

Specific Immunity ◽

Serotype 1

ABSTRACTDengue virus (DENV) is the most common vector-borne viral disease with nearly 400 million worldwide infections each year concentrated in the tropical and subtropical regions of the world. Severe dengue complications are often associated with a secondary heterotypic infection of one of the four circulating serotypes. In this scenario, humoral immune responses targeting cross-reactive, poorly-neutralizing epitopes can lead to increased infectivity of susceptible cells via antibody-dependent enhancement (ADE). In this way, antibodies produced in response to infection or vaccination are capable of contributing to enhanced disease in subsequent infections. Currently, there are no available therapeutics to combat DENV disease, and there is an urgent need for a safe and efficacious vaccine. Here, we developed a nucleotide-modified mRNA vaccine encoding for the membrane and envelope structural proteins from DENV serotype 1 encapsulated into lipid nanoparticles (prM/E mRNA-LNP). Vaccination of mice elicited robust antiviral immune responses comparable to viral infection with high levels of neutralizing antibody titers and antiviral CD4+ and CD8+ T cells. Immunocompromised AG129 mice vaccinated with the prM/E mRNA-LNP vaccine were protected from a lethal DENV challenge. Vaccination with either a wild-type vaccine, or a vaccine with mutations in the immunodominant fusion-loop epitope, elicited equivalent humoral and cell mediated immune responses. Neutralizing antibodies elicited by the vaccine were sufficient to protect against a lethal challenge. Both vaccine constructs demonstrated serotype specific immunity with minimal serum cross-reactivity and reduced ADE compared to a live DENV1 viral infection.IMPORTANCEWith 400 million worldwide infections each year, dengue is the most common vector-born viral disease. 40% of the world’s population is at risk with dengue experiencing consistent geographic spread over the years. With no therapeutics available and vaccines performing sub optimally, the need for an effective dengue vaccine is urgent. Here we develop and characterize a novel mRNA vaccine encoding for the dengue serotype 1 envelope and premembrane structural proteins that is delivered via a lipid nanoparticle. Our DENV1 prM/E mRNA-LNP vaccine induces neutralizing antibody and cellular immune responses in immunocompetent mice and protects an immunocompromised mouse from a lethal DENV challenge. Existing antibodies against dengue can enhance subsequent infections via antibody-dependent enhancement. Importantly our vaccine only induced serotype specific immune responses and did not induce ADE.

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