Cytokines and Viral Gene Products as Regulators of Pterin Synthesis in Cells of the Immune System

Pteridines ◽  
1991 ◽  
Vol 3 (1-2) ◽  
pp. 85-86 ◽  
Author(s):  
K. Schott ◽  
M. Gütlich ◽  
J. Maier ◽  
T. Werner ◽  
I. Ziegler
Keyword(s):  
Immune System ◽  
Viral Gene ◽  
Gene Products ◽  
In Cells

scholarly journals Deletion of Murine Gammaherpesvirus Gene M2 in AID-Expressing B Cells Impairs Host Colonization and Viral Reactivation

2020 ◽  
Author(s):  
Shana M. Owens ◽  
Darby G. Oldenburg ◽  
Douglas W. White ◽  
J. Craig Forrest
Keyword(s):  
Immune System ◽  
B Cells ◽  
B Cell ◽  
Germinal Center ◽  
Viral Reactivation ◽  
Viral Gene ◽  
Gene Products ◽  
Chronic Infections ◽  
Murine Gammaherpesvirus

ABSTRACTGammaherpesviruses (GHVs) are DNA tumor viruses that establish life-long, chronic infections in lymphocytes of humans and other mammals. GHV infections are associated with numerous cancers, especially in immune compromised hosts. While it is known that GHVs utilize host germinal center (GC) B cell responses during latency establishment, an understanding of how viral gene products function in specific B cell subsets to regulate this process is incomplete. Using murine gammaherpesvirus 68 (MHV68) as a small-animal model to define mechanisms of GHV pathogenesis in vivo, we generated a virus in which the M2 gene was flanked by loxP sites (M2.loxP), enabling the use of Cre-lox technology to define M2 function in specific cell types in infection and disease. The M2 gene encodes a protein that is highly expressed in GC B cells that promotes plasma cell differentiation and viral reactivation. M2 was efficiently deleted in Cre-expressing cells, and the presence of loxP sites flanking M2 did not alter viral replication or latency in mice that do not express Cre. In contrast, M2.loxP MHV68 exhibited a deficit in latency establishment and reactivation that resembled M2-null virus, following intranasal (IN) infection of mice that express Cre in all B cells (CD19-Cre). Nearly identical phenotypes were observed for M2.loxP MHV68 in mice that express Cre in germinal center (GC) B cells (AID-Cre). However, neither colonization of draining lymph nodes after IN infection nor the spleen after intraperitoneal (IP) infection required M2, although the reactivation defect was retained. Together, these data confirm that M2 function is B cell-specific and demonstrate that M2 primarily functions in AID-expressing cells to facilitate MHV68 dissemination to distal latency reservoirs within the host and reactivation from latency. Our study reveals that a viral latency gene functions within a distinct subset of cells to facilitate host colonization.IMPORTANCEGammaherpesviruses establish life-long chronic infections in cells of the immune system that can lead to lymphomas and other diseases. To facilitate colonization of a host, gammaherpesviruses encode gene products that manipulate processes involved in cellular proliferation and differentiation. Whether and how these viral gene products function in specific cells of the immune system is poorly defined. We report here the use of a viral genetic system that allows for deletion of specific viral genes in discrete populations of cells. We employ this system in an in vivo model to demonstrate cell-type-specific requirements for a particular viral gene. Our findings reveal that a viral gene product can function in distinct cellular subsets to direct gammaherpesvirus pathogenesis.

scholarly journals Deletion of Murine Gammaherpesvirus Gene M2 in Activation-Induced Cytidine Deaminase-Expressing B Cells Impairs Host Colonization and Viral Reactivation

2020 ◽  
Vol 95 (1) ◽  
Author(s):  
Shana M. Owens ◽  
Darby G. Oldenburg ◽  
Douglas W. White ◽  
J. Craig Forrest
Keyword(s):  
Immune System ◽  
B Cells ◽  
B Cell ◽  
Germinal Center ◽  
Viral Reactivation ◽  
Viral Gene ◽  
Gene Products ◽  
Chronic Infections ◽  
Murine Gammaherpesvirus

ABSTRACT Gammaherpesviruses (GHVs) are DNA tumor viruses that establish lifelong, chronic infections in lymphocytes of humans and other mammals. GHV infections are associated with numerous cancers, especially in immunocompromised hosts. While it is known that GHVs utilize host germinal center (GC) B cell responses during latency establishment, an understanding of how viral gene products function in specific B cell subsets to regulate this process is incomplete. Using murine gammaherpesvirus 68 (MHV68) as a small-animal model to define mechanisms of GHV pathogenesis in vivo, we generated a virus in which the M2 gene was flanked by loxP sites (M2.loxP), enabling the use of Cre-lox technology to define M2 function in specific cell types in infection and disease. The M2 gene encodes a protein that is highly expressed in GC B cells that promotes plasma cell differentiation and viral reactivation. M2 was efficiently deleted in Cre-expressing cells, and the presence of loxP sites flanking M2 did not alter viral replication or latency in mice that do not express Cre. In contrast, M2.loxP MHV68 exhibited a deficit in latency establishment and reactivation that resembled M2-null virus, following intranasal (IN) infection of mice that express Cre in all B cells (CD19-Cre). Nearly identical phenotypes were observed for M2.loxP MHV68 in mice that express Cre in germinal center (GC) B cells (AID-Cre). However, colonization of neither draining lymph nodes after IN infection nor the spleen after intraperitoneal (IP) infection required M2, although the reactivation defect was retained. Together, these data confirm that M2 function is B cell-specific and demonstrate that M2 primarily functions in AID-expressing cells to facilitate MHV68 dissemination to distal latency reservoirs within the host and reactivation from latency. Our study reveals that a viral latency gene functions within a distinct subset of cells to facilitate host colonization. IMPORTANCE Gammaherpesviruses establish lifelong chronic infections in cells of the immune system that can lead to lymphomas and other diseases. To facilitate colonization of a host, gammaherpesviruses encode gene products that manipulate processes involved in cellular proliferation and differentiation. Whether and how these viral gene products function in specific cells of the immune system is poorly defined. We report here the use of a viral genetic system that allows for deletion of specific viral genes in discrete populations of cells. We employ this system in an in vivo model to demonstrate cell-type-specific requirements for a particular viral gene. Our findings reveal that a viral gene product can function in distinct cellular subsets to direct gammaherpesvirus pathogenesis.

Identification of a baculovirus polyhedron formation mutant with a novel phenotype

1996 ◽  
Vol 54 ◽  
pp. 796-797
Author(s):  
James M. Slavicek ◽  
Melissa J. Mercer ◽  
Mary Ellen Kelly
Keyword(s):  
Viral Gene ◽  
Gene Products ◽  
Type Number ◽  
Infection Cycle ◽  
Wild Type ◽  
Protein Matrix ◽  
Insect Midgut ◽  
Viral Particles ◽  
Budded Virus ◽  
Viral Form

Nucleopolyhedroviruses (NPV, family Baculoviridae) produce two morphological forms, a budded virus form and a viral form that is occluded into a paracrystalline protein matrix. This structure is termed a polyhedron and is composed primarily of the protein polyhedrin. Insects are infected by NPVs after ingestion of the polyhedron and release of the occluded virions through dissolution of the polyhedron in the alkaline environment of the insect midgut. Early after infection the budded virus form is produced. It buds through the plasma membrane and then infects other cells. Later in the infection cycle the occluded form of the virus is generated (reviewed by Blissard and Rohrmann, 1990).The processes of polyhedron formation and virion occlusion are likely to involve a number of viral gene products. However, only two genes, the polyhedrin gene and 25K FP gene, have been identified to date that are necessary for the wild type number of polyhedra to be formed and viral particles occluded.

scholarly journals Expression of Opioid Receptors in Cells of the Immune System

2020 ◽  
Vol 22 (1) ◽  
pp. 315
Author(s):  
Jana Brejchova ◽  
Vladimir Holan ◽  
Petr Svoboda
Keyword(s):  
Immune System ◽  
Opioid Receptors ◽  
Methadone Maintenance ◽  
Human Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Immunomodulatory Effects ◽  
Human Peripheral Blood Lymphocytes ◽  
Opioid Drugs ◽  
Human Immune ◽  
In Cells

The observation of the immunomodulatory effects of opioid drugs opened the discussion about possible mechanisms of action and led researchers to consider the presence of opioid receptors (OR) in cells of the immune system. To date, numerous studies analyzing the expression of OR subtypes in animal and human immune cells have been performed. Some of them confirmed the expression of OR at both the mRNA and protein level, while others did not detect the receptor mRNA either. Although this topic remains controversial, further studies are constantly being published. The most recent articles suggested that the expression level of OR in human peripheral blood lymphocytes could help to evaluate the success of methadone maintenance therapy in former opioid addicts, or could serve as a biomarker for chronic pain diagnosis. However, the applicability of these findings to clinical practice needs to be verified by further investigations.

scholarly journals A Nucleolar Protein That Affects Mating Efficiency in Saccharomyces cerevisiae by Altering the Morphological Response to Pheromone

Genetics ◽  
1998 ◽  
Vol 149 (2) ◽  
pp. 795-805
Author(s):  
Jinah Kim ◽  
Jeanne P Hirsch
Keyword(s):  
Growth Regulation ◽  
Subcellular Location ◽  
Null Alleles ◽  
Temperature Sensitive ◽  
Gene Products ◽  
Morphological Response ◽  
Mating Efficiency ◽  
Yeast Genes ◽  
Transcriptional Induction ◽  
In Cells

Abstract SSF1 and SSF2 are redundant essential yeast genes that, when overexpressed, increase the mating efficiency of cells containing a defective Ste4p Gβ subunit. To identify the precise function of these genes in mating, different responses to pheromone were assayed in cells that either lacked or overexpressed SSF gene products. Cells containing null alleles of both SSF1 and SSF2 displayed the normal transcriptional induction response to pheromone but were unable to form mating projections. Overexpression of SSF1 conferred the ability to form mating projections on cells containing a temperature-sensitive STE4 allele, but had only a small effect on transcriptional induction. SSF1 overexpression preferentially increased the mating efficiency of a strain containing a null allele of SPA2, a gene that functions specifically in cell morphology. To investigate whether Ssf1p plays a direct physical role in mating projection formation, its subcellular location was determined. An Ssf1p-GFP fusion was found to localize to the nucleolus, implying that the role of SSF gene products in projection formation is indirect. The region of Ssf1p-GFP localization in cells undergoing projection formation was larger and more diffuse, and was often present in a specific orientation with respect to the projection. Although the function of Ssf1p appears to originate in the nucleus, it is likely that it ultimately acts on one or more of the proteins that is directly involved in the morphological response to pheromone. Because many of the proteins required for projection formation during mating are also required for bud formation during vegetative growth, regulation of the activity or amount of one or more of these proteins by Ssf1p could explain its role in both mating and dividing cells.

Regulation of Metabolism: A Cross Talk Between Gut Microbiota and Its Human Host

Physiology ◽  
2012 ◽  
Vol 27 (5) ◽  
pp. 300-307 ◽  
Author(s):  
Rémy Burcelin
Keyword(s):  
Immune System ◽  
Gut Microbiota ◽  
Low Grade ◽  
Gene Products ◽  
Individual Level ◽  
Obesity And Diabetes ◽  
Regulation Of Metabolism ◽  
Molecular Origin ◽  
The Individual ◽  
Low Grade Inflammation

The recent epidemic of obesity and diabetes and the diversity at the individual level could be explained by the intestinal microbiota-to-host relationship. More than four million gene products from the microbiome could interact with the immune system to induce a tissue metabolic infection, which is the molecular origin of the low-grade inflammation that characterizes the onset of obesity and diabetes.

scholarly journals Varicella-Zoster Virus IE63, a Major Viral Latency Protein, Is Required To Inhibit the Alpha Interferon-Induced Antiviral Response

2007 ◽  
Vol 81 (15) ◽  
pp. 7844-7851 ◽  
Author(s):  
Aruna P. N. Ambagala ◽  
Jeffrey I. Cohen
Keyword(s):  
Varicella Zoster Virus ◽  
Melanoma Cells ◽  
Alpha Interferon ◽  
Parental Virus ◽  
Initiation Factor ◽  
Viral Gene ◽  
Α Subunit ◽  
Varicella Zoster ◽  
In Cells ◽  
Hsv 1

ABSTRACT Varicella-zoster virus (VZV) open reading frame 63 (ORF63) is the most abundant transcript expressed during latency in human sensory ganglia. VZV with ORF63 deleted is impaired for replication in melanoma cells and fibroblasts and for latency in rodents. We found that replication of the ORF63 deletion mutant is fully complemented in U2OS cells, which have been shown to complement the growth of herpes simplex virus type 1 (HSV-1) ICP0 mutants. Since HSV-1 ICP0 mutants are hypersensitive to alpha interferon (IFN-α), we examined the effect of IFN-α on VZV replication. Replication of the ORF63 mutant in melanoma cells was severely inhibited in the presence of IFN-α, in contrast to other VZV mutants that were similarly impaired for replication or to parental virus. The VZV ORF63 mutant was not hypersensitive to IFN-γ. IFN-α inhibited viral-gene expression in cells infected with the ORF63 mutant at a posttranscriptional level. Since IFN-α stimulates gene products that can phosphorylate the α subunit of eukaryotic initiation factor 2 (eIF-2α) and inhibit translation, we determined whether cells infected with the ORF63 mutant had increased phosphorylation of eIF-2α compared with cells infected with parental virus. While phosphorylated eIF-2α was undetectable in uninfected cells or cells infected with parental virus, it was present in cells infected with the ORF63 mutant. Conversely, expression of IE63 (encoded by ORF63) in the absence of other viral proteins inhibited phosphorylation of eIF-2α. Since IFN-α has been shown to limit VZV replication in human skin xenografts, the ability of VZV IE63 to block the effects of the cytokine may play a critical role in VZV pathogenesis.

Induced cellular DNA synthesis by ‘early’ and ‘late’ temperature-sensitive mutants of polyoma virus

1971 ◽  
Vol 177 (1046) ◽  
pp. 59-63 ◽  
Keyword(s):  
Dna Synthesis ◽  
Polyoma Virus ◽  
Viral Gene ◽  
Temperature Sensitive ◽  
Gene Products ◽  
Virus Growth ◽  
Temperature Sensitive Mutants ◽  
Cellular Dna

Temperature-sensitive mutants of polyoma virus have been examined to determine whether they are able to induce the synthesis of cellular DNA under conditions where viral gene products are defective. Two ‘early’ mutants, and one ‘late’ mutant of polyoma induce cellular DNA synthesis normally under conditions where virus growth is inhibited because viral gene products are defective.

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