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Geraniin extracted from the rind of Nephelium lappaceum binds to dengue virus type-2 envelope protein and inhibits early stage of virus replication.

BACKGROUND: The rapid rise and spread in dengue cases, together with the unavailability of safe vaccines and effective antiviral drugs, warrant the need to discover and develop novel anti-dengue treatments. In this study the antiviral activity of geraniin, extracted from the rind of Nephelium lappaceum, against dengue virus type-2 (DENV-2) was investigated. METHODS: Geraniin was prepared from Nephelium lappaceum rind by reverse phase C-18 column chromatography. Cytotoxicity of geraniin towards Vero cells was evaluated using MTT assay while IC50 value was determined by plaque reduction assay.

Attachment of flagellin enhances the immunostimulatory activity of a hemagglutinin-ferritin nano-cage.

Hemagglutinin (HA) displayed on a ferritin nano-cage has been shown to be effective in generating a potent immune response against a broad range of influenza infections. Here, we showed that conjugation of flagellin together with HA to the exterior surface of the ferritin cage greatly enhanced not only the humoral immune response in mice but also antigen-specific T cell responses that include Th1 cytokine secretion. The effect of flagellin remained essentially unchanged when the molar ratio of flagellin to HA was reduced from 1:1 to 1:3. Injection of the ferritin-HA-flagellin cage provided pro

Entry and replication of Japanese encephalitis virus in cultured neurogenic cells.

The entry mode and growth pattern of Japanese encephalitis (JE) virus in mouse neuroblastoma N18TG2 cells and mouse neuroblastoma x rat glioma NG108-15 hybrid cells were studied by electron microscopy. At two minutes after inoculation, JE virions adsorbed onto and directly penetrated through the plasma membrane of the hybrid cells, whereas virions did not adsorb nor entered the neuroblastoma cells. Correspondingly, the hybrid cells showed assembling progeny JE virions in the cisternae of rough endoplasmic reticulum (RER) 1 day postinoculation (p.i.) although virions were rarely found on the fo

Hemagglutinin and fusion proteins precede measles virus ribonucleoproteins and marshal cell-to-cell spread in airway epithelium.

Measles virus (MeV) is the most contagious human respiratory pathogen. To understand how it spreads in the airways, we infected well-differentiated primary cultures of human airway epithelial cells (HAE). We discovered that the MeV attachment protein (hemagglutinin, H), the fusion (F) protein, and the assembly organizer protein (matrix, M) reach newly infected cells ahead of, and independently from, the replicative complex proteins. To characterize the mechanisms of MeV spread, we generated a replication-deficient adenoviral vector expressing the MeV M, F, and H proteins in a doxycycline-induc

Siglec-1-targeted nanobodies restrict HIV-1 transmission and infection of dendritic cells.

UNLABELLED: Human immunodeficiency virus 1 (HIV-1) remains a global health burden affecting over 39 million people worldwide, with approximately one million new infections occurring each year. Sexual transmission remains the predominant route of HIV-1 acquisition, during which the virus crosses mucosal barriers and interacts with host immune cells to facilitate infection. Dendritic cells (DCs) contribute to systemic viral spread and seeding of reservoirs by efficiently capturing HIV-1, leading to infection and subsequent transmission of the virus to CD4+ T cells. Siglec-1 (CD169) is a key rece

Pegylated interferon therapy-related microRNA-6126 downregulates sodium taurocholate cotransporting polypeptide expression in hepatocytes.

Hepatitis B virus (HBV) infection is one of the most serious global health problems. Our previous data using an in vitro assay revealed that miR-6126 suppressed the extracellular HBs antigen level, suggesting that miR-6126 had potential to suppress viral activity of HBV. In the current study, we aimed to clarify whether miR-6126 downregulated the expression level of sodium taurocholate cotransporting polypeptide (NTCP), a host cell receptor required for HBV entry. In brief, HepG2-NTCP cells were utilized to evaluate the expression level of NTCP and the PreS1 attachment to NTCP after transfecti

Lineage pathway of human brain progenitor cells identified by JC virus susceptibility.

Multipotential human central nervous system progenitor cells, isolated from human fetal brain tissue by selective growth conditions, were cultured as undifferentiated, attached cell layers. Selective differentiation yielded highly purified populations of neurons or astrocytes. This report describes the novel use of this cell culture model to study cell type-specific recognition of a human neurotropic virus, JC virus. Infection by either JC virions or a plasmid encoding the JC genome demonstrated susceptibility in astrocytes and, to a lesser degree, progenitor cells, whereas neurons remained no

Role of virus-infected mononuclear leukocytes in herpetic chorioretinitis of newborn rabbits.

The role of virus-infected mononuclear leukocytes (MNLs) in the pathogenesis of neonatal herpetic chorioretinitis in newborn rabbits was investigated. As early as 2 days after inoculating the animals' skins with type 2 herpes simplex virus (HSV-2), infectious MNLs in the infected animals' peripheral blood were found. The virus was associated, for the most part, with MNLs that belonged to phagocytic and adherent cell fractions. Observations by electron microscopy indicated that HSV-2 was actively replicating in the MNLs. It was also found that as few as 80 virus-infected MNLs injected via the r

Development of a virus particle fusion assay to study and target virus entry.

Virus entry leads to the delivery of the viral genome into the target cell for replication and viral gene expression. This critical step is therefore the target of many host immune mechanisms, as well as antiviral drugs. Various experimental systems have been developed to investigate virus entry and test virus entry inhibitors. Often, these systems are either cell-based or employ recombinant proteins to characterize the interaction between viral glycoproteins and their receptors, as well as determine the structural implications of virus attachment and entry. In this study, we have developed a …

Infection and activation of human peripheral blood monocytes by dengue viruses through the mechanism of antibody-dependent enhancement.

Human monocytes are susceptible to dengue virus (DV) infection through an FcR-dependent pathway known as antibody-dependent enhancement (ADE). In this study, infection enhancement was observed when purified monocytes were infected with DV serotypes in the presence of serially diluted immune serum antibodies. Analyzing binding of the DV-antibody immune complexes to monocytes by quantifying the amount of viruses attached to monocytes, we found that binding did not correlate with the input amount of antibodies; rather, it peaked at suboptimal antibody concentrations, correlating with the observed

A nuclear matrix attachment region organizes the Epstein-Barr viral plasmid in Raji cells into a single DNA domain.

The extrachromosomal Epstein-Barr virus (EBV) plasmid in the Burkitt lymphoma cell line, Raji, is stably associated with the nuclear matrix. This association is effected by a nuclear matrix attachment region (MAR) located in the BamHI C fragment of the viral genome; no other region of EBV DNA was found to be attached to the nuclear matrix with high affinity. The MAR was mapped to 5.2 kbp of DNA, greater than 80% of which is found on the nuclear matrix in unsynchronized cells expressing only viral latent cycle products. Thus the majority of viral plasmids in Raji cells use the same MAR. The MAR

Кандидаты на вакцину против наночастиц Mpox-вируса mRNA-lipid вызывают антителную реакцию и защиту от вируса Вакцинии в мышах.

В ответ на эпидемию человека Mpox (HMPX), которая началась в 2022 году, существует срочная потребность в вакцине от обезьяноксика. Здесь мы разработали серию наночастиц на основе mRNA-lipid (mRNA-LNP), которые кодируют коллекцию из четырех высокоохранных поверхностных белков вируса Mpox (MPXV), связанных с соединением, вводом и передачей вируса, а именно A29L, A35R, B6R и M1R, которые являются гомологами вируса Вакцинии (VACV) A27, A33, B5 и L1, соответственно. Несмотря на возможные различия в иммуногенности четырех антигенных mRNA-LNP, управление этими антигенными mRNA-LNP в индивидуальном по

Совпадение в аннотации оригинала
In response to the human Mpox (hMPX) epidemic that began in 2022, there is an urgent need for a monkeypox vaccine. Here, we have developed a series of mRNA-lipid nanoparticle (mRNA-LNP)-based vaccine candidates that encode a collection of four highly conserved Mpox virus (MPXV) surface proteins involved in virus attachment, entry, and transmission, namely A2…

Infection by Zika viruses requires the transmembrane protein AXL, endocytosis and low pH.

The recent Zika virus (ZIKV) outbreak in Brazil has suggested associations of this virus infection with neurological disorders, including microcephaly in newborn infants and Guillian-Barré syndrome in adults. Previous reports have shown that AXL, a transmembrane receptor tyrosine kinase protein, is essential for ZIKV infection of mammalian cells, but this remains controversial. Here, we have assessed the involvement of AXL in the ability of ZIKV to infect mammalian cells, and also the requirement for endocytosis and acidic pH. We demonstrated that AXL is essential for ZIKV infection of human f

The complex co-translational processing of glycoprotein GP5 of type 1 porcine reproductive and respiratory syndrome virus.

GP5 and M, the major membrane proteins of porcine reproductive and respiratory syndrome virus (PRRSV), are the driving force for virus budding and a target for antibodies. We studied co-translational processing of GP5 from an European PRRSV-1 strain. Using mass spectrometry, we show that in virus particles of a Lelystad variant, the signal peptide of GP5 was absent due to cleavage between glycine-34 and asparagine-35. This cleavage site removes an epitope for a neutralizing monoclonal antibody, but leaves intact another epitope recognized by neutralizing pig sera. Upon ectopic expression of th

Purinergic receptor functionality is necessary for infection of human hepatocytes by hepatitis delta virus and hepatitis B virus.

Hepatitis B virus (HBV) and hepatitis delta virus (HDV) are major sources of acute and chronic hepatitis. HDV requires the envelope proteins of HBV for the processes of assembly and infection of new cells. Both viruses are able to infect hepatocytes though previous studies have failed to determine the mechanism of entry into such cells. This study began with evidence that suramin, a symmetrical hexasulfated napthylurea, could block HDV entry into primary human hepatocytes (PHH) and was then extrapolated to incorporate findings of others that suramin is one of many compounds that can block acti

Structural basis of West Nile virus neutralization by a therapeutic antibody.

West Nile virus is a mosquito-borne flavivirus closely related to the human epidemic-causing dengue, yellow fever and Japanese encephalitis viruses. In establishing infection these icosahedral viruses undergo endosomal membrane fusion catalysed by envelope glycoprotein rearrangement of the putative receptor-binding domain III (DIII) and exposure of the hydrophobic fusion loop. Humoral immunity has an essential protective function early in the course of West Nile virus infection. Here, we investigate the mechanism of neutralization by the E16 monoclonal antibody that specifically binds DIII. St

Novel virulence determinants in VP1 regulate the assembly of enterovirus-A71.

UNLABELLED: Enterovirus-A71 (EV-A71) is the second most common causative agent after coxsackievirus A16 of hand, foot, and mouth disease. The capsids of EV-A71 consist of 60 copies of each of the four viral structural proteins (VP1-VP4). VP1 is highly exposed and surface accessible, playing a central role in virus particle assembly, attachment, and entry. To gain insight into the role of highly conserved residues at positions 75, 78, and 88 in the capsid protein VP1 in these processes, an alanine-scanning analysis was performed using an infectious cDNA clone of EV-A71. Our study revealed that

Chronic viral diseases.

Until 20 years ago the only chronic viral diseases known were those considered to be confined to the nervous system. As a result of recent advances in epidemiology, molecular biology and immunology, new viral diseases have been recognized and their clinical features and pathogenesis elucidated. Chronic disease may result from infection with the hepatitis B and D viruses and whatever agent or agents cause hepatitis non-A, non-B, the herpesviruses, Epstein-Barr virus, cytomegalovirus and human T-lymphotropic virus type III. These diseases have common features, including long-term or even lifetim

Complete protection against lethal Nipah virus challenge by intranasal vaccination with bacteriophage T4 coupled with Nipah virus G or F protein.

Nipah virus (NiV) is a highly lethal zoonotic pathogen, causing disease that can spread between animals and people with a mortality rate about 40% to 70%. No commercially approved vaccines or therapeutics are available. In this study, novel NiV vaccines targeting the attachment glycoprotein (G) or fusion glycoprotein (F) of NiV were developed utilizing bacteriophage T4 as a carrier platform. The immune effects induced in mice by intranasal immunization (i.n.) and intramuscular injection (i.m.) show that i.n. immunization with bacteriophage T4 coupled with Nipah virus G or F protein can not onl

Plscr1 inhibits murine norovirus entry.

Noroviruses are a leading cause of gastroenteritis worldwide, yet host factors that restrict norovirus replication are not well understood. By mining both CRISPR activation and CRISPR knockout genome-wide screens, we identified the interferon-stimulated gene Plscr1 as a restriction factor for murine norovirus (MNV). Plscr1 inhibits the fusion of enveloped viruses with endocytic membranes, making its antiviral activity against the nonenveloped MNV surprising. Here, we demonstrate that Plscr1 is both necessary and sufficient to restrict MNV infection in vitro and contributes to the control of co