scholarly journals Understanding the Mechanisms Underlying Host Restriction of Insect-Specific Viruses

Viruses ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 964 ◽  
Author(s):  
Ahmed ME Elrefaey ◽  
Rana Abdelnabi ◽  
Ana Lucia Rosales Rosas ◽  
Lanjiao Wang ◽  
Sanjay Basu ◽  
...  
Keyword(s):  
Structural Genes ◽  
Restriction Factors ◽  
Temperature Dependent ◽  
Complex Interplay ◽  
Mortality And Morbidity ◽  
Host Restriction ◽  
The Past ◽  
Vertebrate Hosts ◽  
Potential Use ◽  
Hematophagous Arthropod

Arthropod-borne viruses contribute significantly to global mortality and morbidity in humans and animals. These viruses are mainly transmitted between susceptible vertebrate hosts by hematophagous arthropod vectors, especially mosquitoes. Recently, there has been substantial attention for a novel group of viruses, referred to as insect-specific viruses (ISVs) which are exclusively maintained in mosquito populations. Recent discoveries of novel insect-specific viruses over the past years generated a great interest not only in their potential use as vaccine and diagnostic platforms but also as novel biological control agents due to their ability to modulate arbovirus transmission. While arboviruses infect both vertebrate and invertebrate hosts, the replication of insect-specific viruses is restricted in vertebrates at multiple stages of virus replication. The vertebrate restriction factors include the genetic elements of ISVs (structural and non-structural genes and the untranslated terminal regions), vertebrate host factors (agonists and antagonists), and the temperature-dependent microenvironment. A better understanding of these bottlenecks is thus warranted. In this review, we explore these factors and the complex interplay between ISVs and their hosts contributing to this host restriction phenomenon.

An atomic-resolution microscope study of Al contracts on GaAs

1986 ◽  
Vol 44 ◽  
pp. 726-727
Author(s):  
Z. Liliental-Weber ◽  
C. Nelson ◽  
R. Ludeke ◽  
R. Gronsky ◽  
J. Washburn
Keyword(s):  
High Speed ◽  
Schottky Contacts ◽  
Detailed Knowledge ◽  
The Past ◽  
Semiconductor Interfaces ◽  
Deposited Metal ◽  
Microwave Applications ◽  
Free Interfaces ◽  
Potential Use

The properties of metal/semiconductor interfaces have received considerable attention over the past few years, and the Al/GaAs system is of special interest because of its potential use in high-speed logic integrated optics, and microwave applications. For such materials a detailed knowledge of the geometric and electronic structure of the interface is fundamental to an understanding of the electrical properties of the contact. It is well known that the properties of Schottky contacts are established within a few atomic layers of the deposited metal. Therefore surface contamination can play a significant role. A method for fabricating contamination-free interfaces is absolutely necessary for reproducible properties, and molecularbeam epitaxy (MBE) offers such advantages for in-situ metal deposition under UHV conditions

scholarly journals Adhesion GPCRs in Glioblastoma

2021 ◽  
Author(s):  
Gabriele Stephan ◽  
Niklas Ravn-Boess ◽  
Dimitris G Placantonakis
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptors ◽  
The Past ◽  
Novel Treatment ◽  
The Family ◽  
Health And Disease ◽  
Basic Biology ◽  
G Protein Coupled ◽  
Potential Use ◽  
Receptor Family

Abstract Members of the adhesion family of G protein-coupled receptors (GPCRs) have received attention for their roles in health and disease, including cancer. Over the past decade, several members of the family have been implicated in the pathogenesis of glioblastoma. Here, we discuss the basic biology of adhesion GPCRs and review in detail specific members of the receptor family with known functions in glioblastoma. Finally, we discuss the potential use of adhesion GPCRs as novel treatment targets in neuro-oncology.

scholarly journals A Productive Expression Platform Derived from Host-Restricted Eilat Virus: Its Extensive Validation and Novel Strategy

Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 660
Author(s):  
Lu Tan ◽  
Yiwen Zhang ◽  
Xingxing Wang ◽  
Dal Young Kim
Keyword(s):  
Expression Vectors ◽  
Structural Genes ◽  
Host Restriction ◽  
Expression Platform ◽  
Mosquito Cells ◽  
Wide Range ◽  
Restriction Property ◽  
Infected Cells ◽  
Multiple Levels ◽  
Novel Strategy

Most alphaviruses are transmitted by mosquitoes and infect a wide range of insects and vertebrates. However, Eilat virus (EILV) is defective for infecting vertebrate cells at multiple levels of the viral life cycle. This host-restriction property renders EILV an attractive expression platform since it is not infectious for vertebrates and therefore provides a highly advantageous safety profile. Here, we investigated the feasibility of versatile EILV-based expression vectors. By replacing the structural genes of EILV with those of other alphaviruses, we generated seven different chimeras. These chimeras were readily rescued in the original mosquito cells and were able to reach high titers, suggesting that EILV is capable of packaging the structural proteins of different lineages. We also explored the ability of EILV to express authentic antigens via double subgenomic (SG) RNA vectors. Four foreign genetic materials of varied length were introduced into the EILV genome, and the expressed heterologous genetic materials were readily detected in the infected cells. By inserting an additional SG promoter into the chimera genome containing the structural genes of Chikungunya virus (CHIKV), we developed a bivalent vaccine candidate against CHIKV and Zika virus. These data demonstrate the outstanding compatibility of the EILV genome. The produced recombinants can be applied to vaccine and diagnostic tool development, but more investigations are required.

scholarly journals Foamy Viruses, Bet, and APOBEC3 Restriction

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 504
Author(s):  
Ananda Ayyappan Jaguva Vasudevan ◽  
Daniel Becker ◽  
Tom Luedde ◽  
Holger Gohlke ◽  
Carsten Münk
Keyword(s):  
Current Knowledge ◽  
Regulatory Protein ◽  
Host Population ◽  
Life Cycles ◽  
Restriction Factors ◽  
Host Restriction ◽  
Open Questions ◽  
Foamy Viruses ◽  
Natural Hosts ◽  
Hiv 1

Non-human primates (NHP) are an important source of viruses that can spillover to humans and, after adaptation, spread through the host population. Whereas HIV-1 and HTLV-1 emerged as retroviral pathogens in humans, a unique class of retroviruses called foamy viruses (FV) with zoonotic potential are occasionally detected in bushmeat hunters or zookeepers. Various FVs are endemic in numerous mammalian natural hosts, such as primates, felines, bovines, and equines, and other animals, but not in humans. They are apathogenic, and significant differences exist between the viral life cycles of FV and other retroviruses. Importantly, FVs replicate in the presence of many well-defined retroviral restriction factors such as TRIM5α, BST2 (Tetherin), MX2, and APOBEC3 (A3). While the interaction of A3s with HIV-1 is well studied, the escape mechanisms of FVs from restriction by A3 is much less explored. Here we review the current knowledge of FV biology, host restriction factors, and FV–host interactions with an emphasis on the consequences of FV regulatory protein Bet binding to A3s and outline crucial open questions for future studies.

Sequence analysis identified an HTLV-1 subtype and mutations of host restriction factors susceptible to HAM/TSP

2017 ◽  
Vol 381 ◽  
pp. 1006
Author(s):  
S. Nozuma ◽  
E. Matsuura ◽  
T. Matsuzaki ◽  
D. Kodama ◽  
R. Kubota ◽  
...  
Keyword(s):  
Sequence Analysis ◽  
Restriction Factors ◽  
Host Restriction ◽  
Host Restriction Factors

Amphotericin b effect on the sensitivity to influenza infection of WI-38 VA-13 cells with IFITM3 gene knockout

2021 ◽  
Vol 21 (3) ◽  
pp. 109-112
Author(s):  
Kira S. Koryabina ◽  
Mariya V. Sergeeva ◽  
Andrey B. Komissarov ◽  
Nataliya V. Eshchenko ◽  
Grigoriy A. Stepanov
Keyword(s):  
Amphotericin B ◽  
Influenza A Virus ◽  
Influenza A ◽  
Gene Knockout ◽  
Influenza Infection ◽  
Restriction Factors ◽  
Host Restriction ◽  
Host Restriction Factors ◽  
Infected Cells ◽  
The Difference

BACKGROUND: The application of CRISPR/Cas9 is one of the most rapidly developing areas in biotechnology. This method was used to obtain clones of а human origin cell line with knockout of one or more genes of the IFITM family, representing host restriction factors for influenza infection. Amphotericin B has previously been shown to promote influenza infection by blocking IFITM3 function. AIM: The aim of this study was to evaluate the effect of amphotericin B on the sensitivity of IFITM knockout cells to influenza A virus infection. MATERIALS AND METHODS: WI-38 VA-13 cells and mutant clones with IFITM3 knockout (F3 clone) or IFITM1, IFITM3 knockout (clone E12) were infected with influenza virus A/PR/8/34 (H1N1) in the presence or absence of amphotericin B. Forty-four hours after infection, the culture medium was taken to determine the infectious activity of the virus by titration in the MDCK cell culture, as well as the hemagglutinating activity of the virus. The infected cells were stained with fluorescently labeled antibodies against the viral NP protein, and the number of NP-positive cells was determined by flow cytometry. RESULTS: The addition of amphotericin B increased the hemagglutinating and infectious activity of the virus in WI-38 VA-13cells, while the difference was insignificant for clones with IFITM gene knockout. A similar dependency was obtained for the percent of infected cells. CONCLUSIONS: Mutant cells with a knockout of one or several genes of the IFITM family were equally susceptible to influenza infection regardless of the addition of amphotericin B, which confirms the crucial importance of a defect in the IFITM3 protein in increasing the permissiveness of cells to influenza A virus.

Host Restriction Factors and Human Immunodeficiency Virus (HIV-1): A Dynamic Interplay Involving All Phases of the Viral Life Cycle

2018 ◽  
Vol 16 (3) ◽  
pp. 184-207 ◽  
Author(s):  
Vanessa D`Urbano ◽  
Elisa De Crignis ◽  
Maria Carla Re
Keyword(s):  
Mammalian Cells ◽  
Viral Evolution ◽  
Type I ◽  
Restriction Factors ◽  
Host Restriction ◽  
Host Restriction Factors ◽  
Immunodeficiency Virus ◽  
Lentiviral Infection ◽  
Specific Proteins ◽  
Hiv 1

Mammalian cells have evolved several mechanisms to prevent or block lentiviral infection and spread. Among the innate immune mechanisms, the signaling cascade triggered by type I interferon (IFN) plays a pivotal role in limiting the burden of HIV-1. In the presence of IFN, human cells upregulate the expression of a number of genes, referred to as IFN-stimulated genes (ISGs), many of them acting as antiviral restriction factors (RFs). RFs are dominant proteins that target different essential steps of the viral cycle, thereby providing an early line of defense against the virus. The identification and characterization of RFs have provided unique insights into the molecular biology of HIV-1, further revealing the complex host-pathogen interplay that characterizes the infection. The presence of RFs drove viral evolution, forcing the virus to develop specific proteins to counteract their activity. The knowledge of the mechanisms that prevent viral infection and their viral counterparts may offer new insights to improve current antiviral strategies. This review provides an overview of the RFs targeting HIV-1 replication and the mechanisms that regulate their expression as well as their impact on viral replication and the clinical course of the disease.

scholarly journals The Emerging Mechanisms of Wnt Secretion and Signaling in Development

2021 ◽  
Vol 9 ◽  
Author(s):  
Shefali Mehta ◽  
Swapnil Hingole ◽  
Varun Chaudhary
Keyword(s):  
Signaling Pathways ◽  
Protein Secretion ◽  
Extracellular Space ◽  
Tissue Homeostasis ◽  
Secreted Proteins ◽  
Complex Interplay ◽  
The Past ◽  
Signaling Mechanisms ◽  
Protein Gradients ◽  
Multiple Signaling

Wnts are highly-conserved lipid-modified secreted proteins that activate multiple signaling pathways. These pathways regulate crucial processes during various stages of development and maintain tissue homeostasis in adults. One of the most fascinating aspects of Wnt protein is that despite being hydrophobic, they are known to travel several cell distances in the extracellular space. Research on Wnts in the past four decades has identified several factors and uncovered mechanisms regulating their expression, secretion, and mode of extracellular travel. More recently, analyses on the importance of Wnt protein gradients in the growth and patterning of developing tissues have recognized the complex interplay of signaling mechanisms that help in maintaining tissue homeostasis. This review aims to present an overview of the evidence for the various modes of Wnt protein secretion and signaling and discuss mechanisms providing precision and robustness to the developing tissues.

Enzyme inhibitors of microbial origin

1980 ◽  
Vol 290 (1040) ◽  
pp. 291-301 ◽  
Keyword(s):  
Enzyme Inhibitors ◽  
Future Research ◽  
Main Interest ◽  
Porcine Pancreas ◽  
The Past ◽  
Microbial Origin ◽  
Irreversible Inhibitors ◽  
Antibiotic Agents ◽  
Potential Use ◽  
New Metabolites

The screening for enzyme inhibitors of microbial origin in the past decades has been a prosperous area to find new metabolites that are of potential importance as therapeutic or antibiotic agents. This review attempts a survey of recent achievements in this type of screening. Special emphasis is given to enzyme inhibitors and screening systems in fields where industry has a main interest in development. This includes some notes on the improved methodology for the detection of reversible and irreversible inhibitors of β-lactamases and the presentation of a unique inhibitor of α-amylase from porcine pancreas isolated from a strain of Streptomyces tendae . This inhibitor (HOE 467) may be of potential use in the treatment of diabetic conditions, obesity and adipositas. The results show that the screening for enzyme inhibitors from microorganisms still provides one of the central challenges for future research.

Group B Streptococcal Infections in Neonates

1979 ◽  
Vol 1 (1) ◽  
pp. 5-15
Author(s):  
Carol J. Baker
Keyword(s):  
Group B Streptococcus ◽  
Newborn Infants ◽  
Neonatal Infection ◽  
Etiologic Agent ◽  
Diagnostic Methods ◽  
Bacterial Disease ◽  
Absolute Increase ◽  
Mortality And Morbidity ◽  
The Past ◽  
Group B

β-Hemolytic streptococci of Lancefield group B have been causally linked to neonatal disease since 1938, but only in the last decade has the group B Streptococcus become the leading etiologic agent for bacteremia and/or meningitis occurring during the first two months of life. Neither the reasons for the emergence of this organism nor the shifts over the past 40 years in the prevalence of various bacteria responsible for neonatal infection has been adequately explained. However, the importance of the group B Streptococcus as a frequent cause of neonatal mortality and morbidity demands a thorough understanding of the epidemiology and pathogenesis, clinical features, diagnostic methods, and management of these infections by physicians caring for newborn infants. INCIDENCE The common occurrence of neonatal group B streptococcal septicemia and meningitis in several geographically distant centers since 1970 has allowed the relatively precise determination of attack rates for early onset type (≤5 days) infection. Reported attack rates have been surprisingly uniform, varying from 1.3/1,000 to 4.0/1,000 live births (Table 1). Because the attack rates for serious neonatal infections associated with Escherichia coli and other maternally acquired coliform organisms have been constant since 1960, the appearance of the group B Streptococcus resulted in an absolute increase in the incidence of neonatal bacterial disease during the past decade in many hospitals in this country.

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