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Identification of Unique Peptides for SARS-CoV-2 Diagnostics and Vaccine Development by an In Silico Proteomics Approach.

Ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus strains is posing new COVID-19 diagnosis and treatment challenges. To help efforts to meet these challenges we examined data acquired from proteomic analyses of human SARS-CoV-2-infected cell lines and samples from COVID-19 patients. Initially, 129 unique peptides were identified, which were rigorously evaluated for repeats, disorders, polymorphisms, antigenicity, immunogenicity, toxicity, allergens, sequence similarity to human proteins, and contributions from other potential cross-reacting pathogenic spec

Salinomycin Inhibits Influenza Virus Infection by Disrupting Endosomal Acidification and Viral Matrix Protein 2 Function.

Screening of chemical libraries with 2,000 synthetic compounds identified salinomycin as a hit against influenza A and B viruses, with 50% effective concentrations ranging from 0.4 to 4.3 μM in cells. This compound is a carboxylic polyether ionophore that exchanges monovalent ions for protons across lipid bilayer membranes. Monitoring the time course of viral infection showed that salinomycin blocked nuclear migration of viral nuclear protein (NP), the most abundant component of the viral ribonucleoprotein (vRNP) complex. It caused cytoplasmic accumulation of NP, particularly within perinuclea

TRIM41-Mediated Ubiquitination of Nucleoprotein Limits Influenza A Virus Infection.

Influenza A virus (IAV) is a highly transmissible respiratory pathogen and a major cause of morbidity and mortality around the world. Nucleoprotein (NP) is an abundant IAV protein essential for multiple steps of the viral life cycle. Our recent proteomic study of the IAV-host interaction network found that TRIM41 (tripartite motif-containing 41), a ubiquitin E3 ligase, interacted with NP. However, the role of TRIM41 in IAV infection is unknown. Here, we report that TRIM41 interacts with NP through its SPRY domain. Furthermore, TRIM41 is constitutively expressed in lung epithelial cells, and ov

Influenza A viruses escape from MxA restriction at the expense of efficient nuclear vRNP import.

To establish a new lineage in the human population, avian influenza A viruses (AIV) must overcome the intracellular restriction factor MxA. Partial escape from MxA restriction can be achieved when the viral nucleoprotein (NP) acquires the critical human-adaptive amino acid residues 100I/V, 283P, and 313Y. Here, we show that introduction of these three residues into the NP of an avian H5N1 virus renders it genetically unstable, resulting in viruses harboring additional single mutations, including G16D. These substitutions restored genetic stability yet again yielded viruses with varying degrees

Unravelling the genetic components involved in the immune response of pigs vaccinated against influenza virus.

A genome-wide association study for immune response to influenza vaccination in a crossbred swine population was conducted. Swine influenza is caused by influenza A virus (FLUAV) which is considered one of the most prevalent respiratory pathogens in swine worldwide. The main strategy used to control influenza in swine herds is through vaccination. However, the currently circulating FLUAV subtypes in swine are genetically and antigenically diverse and their interaction with the host genetics poses a challenge for the production of efficacious and cross-protective vaccines. In this study, 103 pi

Broadly protective immunity against divergent influenza viruses by oral co-administration of Lactococcus lactis expressing nucleoprotein adjuvanted with cholera toxin B subunit in mice.

BACKGROUND: Current influenza vaccines need to be annually reformulated to well match the predicated circulating strains. Thus, it is critical for developing a novel universal influenza vaccine that would be able to confer cross-protection against constantly emerging divergent influenza virus strains. Influenza virus A is a genus of the Orthomyxoviridae family of viruses. Influenza virus nucleoprotein (NP) is a structural protein which encapsidates the negative strand viral RNA, and anti-NP antibodies play role in cross-protective immunity. Lactococcus lactis (L. lactis) is an ideal vaccine de

Mutations to PB2 and NP proteins of an avian influenza virus combine to confer efficient growth in primary human respiratory cells.

UNLABELLED: Influenza pandemics occur when influenza A viruses (IAV) adapted to other host species enter humans and spread through the population. Pandemics are relatively rare due to host restriction of IAV: strains adapted to nonhuman species do not readily infect, replicate in, or transmit among humans. IAV can overcome host restriction through reassortment or adaptive evolution, and these are mechanisms by which pandemic strains arise in nature. To identify mutations that facilitate growth of avian IAV in humans, we have adapted influenza A/duck/Alberta/35/1976 (H1N1) (dk/AB/76) virus to a

Молекулярная характеристика вирусных штаммов кори, вызывающих склерозный панэнцефалит во Франции в 1977 и 2007 годах.

Были изучены штаммы кори от двух случаев склерозного панэнцефалита (SSPE), диагностированных в 1977 году (деформация легких) и в 2007 году (трясение подопытных). Филогенетический анализ, основанный на С-терминальной части нуклеопротеина и всего гена H, показал, что штамм Hoedts, циркулирующий во Франции предположительно в 1980-х годах, принадлежал генотипу C2. Однако штамм Лейна, который предположительно распространился в период с 1940-х по 1960-е годы, не может быть присвоен каким-либо известным генотипам кори. Анализ последовательности штамма Лейна показал, что он возник из вируса кори, кото

Amino acids at positions 273 and 394 in rabies virus nucleoprotein are important for both evasion of host RIG-I-mediated antiviral response and pathogenicity.

We previously reported that nucleoprotein (N) is related to the different pathogenicities of the virulent rabies virus strain Nishigahara (Ni) and avirulent strain Ni-CE and also that Ni N, but not Ni-CE N, functions to evade retinoic acid-inducible gene I (RIG-I)-mediated innate immunity. There are three amino acid differences between Ni and Ni-CE N (at positions 273, 394 and 395), indicating that one of these mutations or a combination of mutations is important for the pathogenicity and evasion of innate immunity. We generated Ni-CE mutants in which the amino acids in Ni-CE N were replaced w

Chondrocyte antigen expression, immune response and susceptibility to arthritis.

The association of HLA-B27 with certain forms of arthritis implies a role for MHC class I-restricted T cells in the arthritic process. Our aim was to study CD8(+) T cell responses towards specific antigens localized in joint tissue. Known determinants were introduced into chondrocytes of transgenic (TG) mice, under the control of the cis-regulatory sequences of the human type II collagen gene (COL2A1). Two Escherichia coli beta-galactosidase (beta-gal)-expressing lines were derived (CIIL73 and CIIL64) as well as two lines (CIINP) expressing influenza A virus nucleoprotein (NP). Expression of t

Coronavirus membrane protein with a fluorescent protein tag enables particle tracking for the study of virus assembly and egress in live cells.

UNLABELLED: Coronavirus particles assemble at endoplasmic reticulum-Golgi intermediate compartment (ERGIC) membranes and exit from host cell … the scaffold for the assembly of the viral envelope. It facilitates the incorporation of the viral nucleocapsid and the other viral membrane proteins, spike (S) and envelope (E). In this study, we engineered the M protein tagged with green fluorescent protein (GFP), which is expressed along with wild-type (WT) M from the viral genome. M-GFP interacted with WT …

Temperature-modulated persistent dsRNA phage infection selectively excludes superinfection and promotes generation of new viral variants.

UNLABELLED: Persistent viral infections are common in nature and can play a significant role in the ecology and evolution of the host organi … change between related phages. Accordingly, P8 of phi6 specifically inhibited transcription by phi6 nucleocapsids but did not suppress transcription of a related phage in an in vitro transcription assay. This study sheds light on the underlying molecular mechanisms and potential ecological implications of persistent dsRNA phage infection in plant pathogenic Ps …

Preclinical Evaluation of the Efficacy of α-Difluoromethylornithine and Sulindac Against SARS-CoV-2 Infection.

Despite numerous research efforts and several effective vaccines and therapies developed against coronavirus disease 2019 (COVID-19), drug r … the infected human cell lines, the DFMO/Sulindac combination significantly suppressed SARS-CoV-2 N1 Nucleocapsid mRNA by interacting synergistically when cells were pretreated with drugs and additively when treatment was applied to the infected cells. The Sulindac alone and DFMO/Sulindac combination treatments also suppressed the expression of the viral Spike …

Serologic, Virologic and Pathologic Features of Cats with Naturally Occurring Feline Infectious Peritonitis Enrolled in Antiviral Clinical Trials.

Feline infectious peritonitis (FIP) is a multisystemic, generally lethal immuno-inflammatory disease of domestic cats caused by an infection … ust throughout the treatment period, primarily the IgG isotype, and focused on the viral structural Nucleocapsid and Membrane proteins. Coronavirus serologic patterns were similar for the effusions and serum/plasma of cats with FIP and in cats entering remission or that died. Viral RNA was readily detectable in the majority of the cats in either abdominal lymp …

Evidence for residual SARS-CoV-2 in corpus cavernosum of patients who recovered from COVID-19 infection.

BACKGROUND: The COVID-19 is an ongoing health problem with millions of cases and deaths worldwide. Although the virus is transmitted with dr … l particles of about 80 nm with a typical morphology of prominent spikes and electron-dense dots of nucleocapsid in addition to vesicles filled with virus-like particles. Cells showed increased membrane trafficking. The 1 month after COVID-19 group showed an increased number of fibroblasts. The 7 months after COVID-19 group had similar morphology and immunorea …

KSHV ORF20 Interacts с Viral Probein Factory ORF59 и поощряет вирусную реактивацию.

После того как герпесвирус (KSHV) был связан с герпесом Капози, быстрое и широкомасштабное усиление вирусной ДНК (VDNA) приводит к значительной ядерной реорганизации. В рамках этого поразительного сдвига в ядерной архитектуре вирусные репродукционные отсеки формируются как места производства литических VDNA наряду с замечательной пространственной реконструкцией и релокацией клеточных и вирусных белков. В этих вирусных репликационных отсеках содержится несколько литических генопродуктов, которые координируют вирусное выражение генов, репликацию vDNA и сборку нуклеокапсидов. Виртуальные белки и

Совпадение в аннотации оригинала
Upon Kaposi's Sarcoma-associated herpesvirus (KSHV) lytic reactivation, rapid and widespread amplification of viral DNA (vDNA) triggers sign … ents house several lytic gene products that coordinate viral gene expression, vDNA replication, and nucleocapsid assembly. The viral proteins and mechanisms that regulate this overhaul of the nuclear landscape during KSHV replication remain largely unknown. KSHV's ORF20 is a widely conserved lytic gene among all herpesviruses, suggesting it may have a fundamen …

Dynamin Is Required for Efficient Cytomegalovirus Maturation and Envelopment.

Cytomegalovirus secondary envelopment occurs in a virus-induced cytoplasmic assembly compartment (vAC) generated via a drastic reorganizatio … nalysis revealed intact stages of nuclear virus maturation in both cases with equivalent numbers of nucleocapsids containing packaged viral DNA (C-capsids), indicating successful viral DNA replication, capsid assembly, and genome packaging. Most importantly, severe defects in virus envelopment were visualized in TKO cells but not in parental cells. Dynamin inh …

Preclinical evaluation of a mercaptobenzamide and its prodrug for NCp7-targeted inhibition of human immunodeficiency virus.

Although the effective use of highly active antiretroviral therapy results in the suppression of virus production in infected individuals, i … ug (NS1040) are being developed as potential therapeutic compounds targeting the zinc finger of HIV nucleocapsid. In the presence of esterase enzymes, NS1040 is designed to be converted to MDH-1-38 which has antiviral activity. While we presume that NS1040 is rapidly converted to MDH-1-38 in all experiments, the two compounds were tested side-by-side to determ …

trans-Protease activity and structural insights into the active form of the alphavirus capsid protease.

The alphavirus capsid protein (CP) is a serine protease that possesses cis-proteolytic activity essential for its release from the nascent structural polyprotein. The released CP further participates in viral genome encapsidation and nucleocapsid core formation, followed by its attachment to glycoproteins and virus budding. Thus, protease activity of the alphavirus capsid is a potential antialphaviral target to arrest capsid release, maturation, and structural polyprotein processing. However, the discovery of capsid protease inhibitors has been hampered due to the lack of a suitable screening …

Coronavirus immunogens.

Coronaviruses (CV) infect a variety of livestock, poultry and companion animals. They belong to at least five antigenic groups. CV cause loc … the spike (S) glycoprotein (150-200 kDa), the integral membrane glycoprotein (M; 20-30 kDa) and the nucleocapsid phosphoprotein (N; 43-50 kDa). A subset of CV (BCV, HEV, turkey CV) possess a third glycoprotein on the virion surface, the HE (60-65 kDa). These proteins can be quantitated using pooled monoclonal antibodies (mAb) to distinct epitopes of each prote …