Relationship Between Cell Surface Viral Glycoprotein Expression and Resistance of Parainfluenza Virus Persistently Infected Cells to Complement-Mediated Lysis.

Persistent RNA virus infections (PI) are often characterized by extended viral shedding and maintained cycles of inflammation. The innate immune Complement (C') pathways can recognize acute infected (AI) cells and result in their lysis, but the relative sensitivity of PI cells to C'-directed killing is incompletely understood. Here, we extended our previous studies on the interactions of C' with parainfluenza virus AI and PI A549 cells to two additional respiratory tract cell lines.

A Type I IFN-Inducing Oncolytic Virus Improves NK Cell-Mediated Killing of Tumor Cells In Vitro Through Multiple Mechanisms.

Natural killer (NK) cell adoptive immunotherapy is a promising therapeutic approach in which NK cells perform targeted lysis of tumor cells. Oncolytic viruses are also effective cancer therapeutic agents due to their ability to selectively target and kill tumor cells. Combination therapies that integrate NK cells and oncolytic viruses have been shown to enhance tumor killing compared to individual treatment strategies alone.

Role of Defective Interfering Particles in Complement-Mediated Lysis of Parainfluenza Virus-Infected Cells.

RNA viruses pose a significant global public health burden due to their high mutation rates, zoonotic potential, and ability to evade immune responses. A common aspect of their replication is the generation of defective interfering particles (DIPs), which contain truncated defective viral genomes (DVGs) that depend on full-length standard (STD) virus for replication. DVGs have gained recognition as they are increasingly detected in clinical samples from natural infections.

Resistance to complement-mediated lysis of parainfluenza virus 5-infected cells is acquired after transition from acute to persistent infection.

Unlabelled: Persistent viral infections can be an important medical problem, with persistently infected (PI) cells extending viral shedding, maintaining inflammation, and providing potential sources for new viral variants. Given that PI cells can acquire resistance to some innate immune pathways, we tested the hypothesis that complement (C')-mediated lysis of parainfluenza virus 5 (PIV5)-infected cells would differ between acute-infected and PI cells. Biochemical and real-time cell viability assays showed effective C'-mediated lysis of A549 lung cells acutely infected with PIV5, through pathways that depended on C3 and C5, but largely independent of C6.

Parainfluenza Virus 5 V Protein Blocks Interferon Gamma-Mediated Upregulation of NK Cell Inhibitory Ligands and Improves NK Cell Killing of Neuroblastoma Cells.

Natural killer (NK) cells can be effective immunotherapeutic anti-cancer agents due to their ability to selectively target and kill tumor cells. This activity is modulated by the interaction of NK cell receptors with inhibitory ligands on the surface of target cells. NK cell inhibitory ligands can be upregulated on tumor cell surfaces in response to interferon-gamma (IFN-γ), a cytokine which is produced by activated NK cells.

Broad-Spectrum, Potent, and Durable Ceria Nanoparticles Inactivate RNA Virus Infectivity by Targeting Virion Surfaces and Disrupting Virus-Receptor Interactions.

There is intense interest in developing long-lasting, potent, and broad-spectrum antiviral disinfectants. Ceria nanoparticles (CNPs) can undergo surface redox reactions (Ce ↔ Ce) to generate ROS without requiring an external driving force. Here, we tested the mechanism behind our prior finding of potent inactivation of enveloped and non-enveloped RNA viruses by silver-modified CNPs, AgCNP1 and AgCNP2.

DNA methyltransferase inhibitor 5-azacytidine enhances neuroblastoma cell lysis by an oncolytic parainfluenza virus.

Studies with neuroblastoma have shown that the presence of aberrant DNA epigenetic modifications mediated by DNA methyltransferases correlates with poor prognosis, making these enzymes a target for therapeutics based on synthetic epigenetic modulators such as DNA methyltransferase inhibitors (DNMTi). Here, we have used a neuroblastoma cell line model to test the hypothesis that treatment with a DNMTi would enhance cell killing when used in combination with oncolytic Parainfluenza virus 5 (P/V virus), a cytoplasmic-replicating RNA virus. Pretreatment of SK-N-AS cells with the DNMTi 5-azacytidine substantially enhanced P/V virus-mediated cell death in a dose- and multiplicity of infection-dependent manner.

Delivery of a novel membrane-anchored Fc chimera enhances NK cell-mediated killing of tumor cells and persistently virus-infected cells.

Antibody-dependent cellular cytotoxicity (ADCC) is one of the most powerful mechanisms for Natural Killer (NK) cells to kill cancer cells or virus-infected cells. A novel chimeric protein (NA-Fc) was created, which when expressed in cells, positions an IgG Fc domain on the plasma membrane, mimicking the orientation of IgG bound to the cell surface. This NA-Fc chimera was tested with PM21-NK cells, produced through a previously developed particle-based method which yields superior NK cells for immunotherapeutic applications.

CD24 Expression Dampens the Basal Antiviral State in Human Neuroblastoma Cells and Enhances Permissivity to Zika Virus Infection.

Zika virus (ZIKV) exhibits distinct selectivity for infection of various cells and tissues, but how host cellular factors modulate varying permissivity remains largely unknown. Previous studies showed that the neuroblastoma cell line SK-N-AS (expressing low levels of cellular protein CD24) was highly restricted for ZIKV infection, and that this restriction was relieved by ectopic expression of CD24. We tested the hypothesis that CD24 expression allowed ZIKV replication by suppression of the antiviral response.

Potent Inactivation of Human Respiratory Viruses Including SARS-CoV-2 by a Photoactivated Self-Cleaning Regenerative Antiviral Coating.

The COVID-19 pandemic marks an inflection point in the perception and treatment of human health. Substantial resources have been reallocated to address the direct medical effects of COVID-19 and to curtail the spread of the virus. Thereby, shortcomings of traditional disinfectants, especially their requirement for regular reapplication and the related complications (e.

ALD based nanostructured zinc oxide coated antiviral silk fabric.

The COVID-19 pandemic has underscored the importance of research and development in maintaining public health. Facing unprecedented challenges, the scientific community developed antiviral drugs, virucides, and vaccines to combat the infection within the past two years. However, an ever-increasing list of highly infectious SARS-CoV-2 variants (gamma, delta, omicron, and now ba.

Differential In Vitro Growth and Cell Killing of Cancer versus Benign Prostate Cells by Oncolytic Parainfluenza Virus.

The development of effective oncolytic viruses will require understanding the differences in virus replication and killing between normal and cancer cells. Here, we have evaluated infections of metastatic cancer (22Rv1) and benign non-tumorigenic (BPH-1) prostate cell lines with a mutant parainfluenza virus 5 (P/V/F) encoding a defective V protein and a hyperfusogenic F protein. Under low multiplicity of infection (MOI), the P/V/F mutant efficiently spread in 22Rv1 cells but was restricted in BPH-1 cells due to type-I interferon (IFN-I) responses.

Complement Inhibitors Vitronectin and Clusterin Are Recruited from Human Serum to the Surface of Coronavirus OC43-Infected Lung Cells through Antibody-Dependent Mechanisms.

Little is known about the role of complement (C') in infections with highly prevalent circulating human coronaviruses such as OC43, a group of viruses of major public health concern. Treatment of OC43-infected human lung cells with human serum resulted in C3 deposition on their surfaces and generation of C5a, indicating robust C' activation. Real-time cell viability assays showed that in vitro C'-mediated lysis of OC43 infected cells requires C3, C5 and C6 but not C7, and was substantially delayed as compared to rapid C'-mediated killing of parainfluenza virus type 5 (PIV5)-infected cells.

Metal-Mediated Nanoscale Cerium Oxide Inactivates Human Coronavirus and Rhinovirus by Surface Disruption.

The COVID19 pandemic has brought global attention to the threat of emerging viruses and to antiviral therapies, in general. In particular, the high transmissibility and infectivity of respiratory viruses have been brought to the general public's attention, along with the need for highly effective antiviral and disinfectant materials/products. This study has developed two distinct silver-modified formulations of redox-active nanoscale cerium oxide (AgCNP1 and AgCNP2).

Oncolytic parainfluenza virus combines with NK cells to mediate killing of infected and non-infected lung cancer cells within 3D spheroids: role of type I and type III interferon signaling.

Background: There is intense interest in developing novel oncolytic viruses, which can be used in cancer therapies along with immune cells such as natural killer (NK) cells. We have previously developed a particle-based method for in vitro expansion of highly cytotoxic human NK cells (PM21-NK cells). Here, we have tested the hypothesis that oncolytic parainfluenza virus 5 (P/V virus) can combine with PM21-NK cells for targeted killing of lung cancer cells.

Enhancement of infectivity of insect cell-derived La Crosse Virus by human serum.

Given the dual life cycle of arboviruses in insect and animal hosts and the importance of serum factors as a first line antiviral defense, we have examined the outcome of interactions between the arbovirus La Crosse Virus (LACV) and human serum. To mimic the life cycle between species, we used LACV derived from insect (I-LACV) and human keratinocyte (HaCaT) cells. Incubation of I-LACV with normal human serum did not result in neutralization, but instead stabilized I-LACV virions and enhanced the amount of infectious virus.

La Crosse Virus Infection of Human Keratinocytes Leads to Interferon-Dependent Apoptosis of Bystander Non-Infected Cells In Vitro.

Resident cells in the skin serve as the first innate line of defense against insect-borne pathogens, but the role of these cell types in promoting or limiting arbovirus replication is not completely understood. Here, we have examined the outcome of infection of cultured human keratinocyte cells with La Crosse virus (LACV), using a spontaneously transformed cell line, HaCaT. In single cycle infections, keratinocyte HaCaT cells supported rapid and high level LACV replication, resulting in high virus yields and extensive caspase-dependent cell death.

Aptamer-gold nanoparticle conjugates for the colorimetric detection of arboviruses and vector mosquito species.

The real-time, colorimetric detection of analytes aptamer-gold nanoparticle technology has proven to be an important, emerging technique within the medical field. Of global health importance, the ability to detect vector mosquito species, such as the () mosquito, and transmitted arboviruses, such as Zika virus, is paramount to mosquito control and surveillance efforts. Herein, we describe the detection of salivary protein for vector identification and the detection of Zika virus to assess mosquito infection status by aptamer-gold nanoparticle conjugates.

A porcine xenograft-derived bone scaffold is a biocompatible bone graft substitute: An assessment of cytocompatibility and the alpha-Gal epitope.

Background: Xenografts are an attractive alternative to traditional bone grafts because of the large supply from donors with predictable morphology and biology as well as minimal risk of human disease transmission. Clinical series involving xenograft bone transplantation, most commonly from bovine sources, have reported poor results with frequent graft rejection and failure to integrate with host tissue. Failures have been attributed to residual alpha-Gal epitope in the xenograft which humans produce natural antibody against.

Histone Deacetylase Inhibitors Enhance Cell Killing and Block Interferon-Beta Synthesis Elicited by Infection with an Oncolytic Parainfluenza Virus.

Previous results have shown that infection with the cytoplasmic-replicating parainfluenza virus 5 mutant P/V-CPI- sensitizes cells to DNA damaging agents, resulting in the enhanced killing of airway cancer cells. Here, we have tested the hypothesis that histone deacetylase (HDAC) inhibitors can also act with P/V-CPI- infection to enhance cancer cell killing. Using human small cell lung cancer and laryngeal cancer cell lines, 10 HDAC inhibitors were tested for their effect on viability of P/V-CPI- infected cells.

Zika virus as an oncolytic treatment of human neuroblastoma cells requires CD24.

Neuroblastoma is the second most common childhood tumor. Survival is poor even with intensive therapy. In a search for therapies to neuroblastoma, we assessed the oncolytic potential of Zika virus.

Relative Contribution of Cellular Complement Inhibitors CD59, CD46, and CD55 to Parainfluenza Virus 5 Inhibition of Complement-Mediated Neutralization.

The complement system is a part of the innate immune system that viruses need to face during infections. Many viruses incorporate cellular regulators of complement activation (RCA) to block complement pathways and our prior work has shown that Parainfluenza virus 5 (PIV5) incorporates CD55 and CD46 to delay complement-mediated neutralization. In this paper, we tested the role of a third individual RCA inhibitor CD59 in PIV5 interactions with complement pathways.

Parainfluenza Virus Infection Sensitizes Cancer Cells to DNA-Damaging Agents: Implications for Oncolytic Virus Therapy.

A parainfluenza virus 5 (PIV5) with mutations in the P/V gene (P/V-CPI) is restricted for spread in normal cells but not in cancer cells and is effective at reducing tumor burdens in mouse model systems. Here we show that P/V-CPI infection of HEp-2 human laryngeal cancer cells results in the majority of the cells dying, but unexpectedly, over time, there is an emergence of a population of cells that survive as P/V-CPI persistently infected (PI) cells. P/V-CPI PI cells had elevated levels of basal caspase activation, and viability was highly dependent on the activity of cellular inhibitor-of-apoptosis proteins (IAPs) such as Survivin and XIAP.

Adjuvanting an inactivated influenza vaccine with flagellin improves the function and quantity of the long-term antibody response in a nonhuman primate neonate model.

Young infants are at significantly increased risk of developing severe disease following infection with influenza virus. At present there is no approved vaccine for individuals below the age of six months given previous studies showing a failure of these individuals to efficiently seroconvert. Given the major impact of influenza on infant health, it is critical that we develop vaccines that will be safe and effective in this population.

Parainfluenza virus 5 upregulates CD55 expression to produce virions with enhanced resistance to complement-mediated neutralization.

Many enveloped RNA viruses recruit host cell proteins during assembly as a mechanism to limit antiviral effects of complement. Using viruses which incorporated CD46 alone, CD55 alone or both CD46 and CD55, we addressed the role of these two host cell regulators in limiting complement-mediated neutralization of Parainfluenza virus 5 (PIV5). PIV5 incorporated functional forms of both CD55 and CD46 into virions.