scholarly journals Nonprofessional Phagocytosis Can Facilitate Herpesvirus Entry into Ocular Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Vaibhav Tiwari ◽  
Deepak Shukla
Keyword(s):  
Epithelial Cells ◽  
Actin Polymerization ◽  
Retinal Pigment ◽  
Human Herpesvirus ◽  
Transmission Electron Microscopy Data ◽  
Common Mechanism ◽  
Successful Infection ◽  
Membrane Protrusions ◽  
Human Herpesviruses ◽  
Hsv 1

Phagocytosis is a major mechanism by which the mediators of innate immunity thwart microbial infections. Here we demonstrate that human herpesviruses may have evolved a common mechanism to exploit a phagocytosis-like entrapment to gain entry into ocular cells. While herpes simplex virus-1 (HSV-1) causes corneal keratitis, cytomegalovirus (CMV) is associated with retinitis in immunocompromised individuals. A third herpesvirus, human herpesvirus-8 (HHV-8), is crucial for the pathogenesis of Kaposi’s sarcoma, a common AIDS-related tumor of eyelid and conjunctiva. Using laser scanning confocal microscopy, we show that successful infection of ocular cell types by all the three viruses, belonging to three divergent subfamilies of herpesviruses, is facilitated by induction of F-actin rich membrane protrusions. Inhibitors of F-actin polymerization and membrane protrusion formation, cytochalasin D and latrunculin B, were able to block infection by all three viruses. Similar inhibition was seen by blocking phosphoinositide 3 kinase signaling, which is required for microbial phagocytosis. Transmission electron microscopy data using human corneal fibroblasts for HSV-1, human retinal pigment epithelial cells for CMV, and human conjunctival epithelial cells for HHV-8 are consistent with the possibility that pseudopod-like membrane protrusions facilitate virus uptake by the ocular cells. Our findings suggest a novel mechanism by which the nonprofessional mediators of phagocytosis can be infected by human herpesviruses.

scholarly journals Association of cognitive function and liability to addiction with childhood herpesvirus infections: A prospective cohort study

2017 ◽  
Vol 30 (1) ◽  
pp. 143-152 ◽  
Author(s):  
Michael M. Vanyukov ◽  
Vishwajit L. Nimgaonkar ◽  
Levent Kirisci ◽  
Galina P. Kirillova ◽  
Maureen D. Reynolds ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Human Herpesvirus ◽  
Cognitive Mechanisms ◽  
Barr Virus ◽  
Path Analyses ◽  
Males And Females ◽  
Epstein Barr ◽  
Human Herpesviruses ◽  
Hsv 1

AbstractLiability to substance use disorder (SUD) is largely nonspecific to particular drugs and is related to behavior dysregulation, including reduced cognitive control. Recent data suggest that cognitive mechanisms may be influenced by exposure to neurotropic infections, such as human herpesviruses. In this study, serological evidence of exposure to human herpesvirus Herpes simplex virus Type 1 (HSV-1), cytomegalovirus (CMV), and Epstein–Barr virus (EBV) as well as Toxoplasma gondii was determined in childhood (age ~11 years) in 395 sons and 174 daughters of fathers with or without SUD. Its relationships with a cognitive characteristic (IQ) in childhood and with risk for SUD in adulthood were examined using correlation, regression, survival, and path analyses. Exposure to HSV-1, EBV, and T. gondii in males and females, and CMV in males, was associated with lower IQ. Independent of that relationship, EBV in females and possibly in males, and CMV and possibly HSV-1 in females were associated with elevated risk for SUD. Therefore, childhood neurotropic infections may influence cognitive development and risk for behavior disorders such as SUD. The results may point to new avenues for alleviating cognitive impairment and SUD risk.

scholarly journals PCR detection of multiple human herpesvirus DNA in saliva from HIV-infected individuals in Teresina, State of Piauí, Brazil

2010 ◽  
Vol 43 (6) ◽  
pp. 620-623 ◽  
Author(s):  
Kátia Silene Sousa Carvalho ◽  
Ellida de Aguiar Silvestre ◽  
Samira da Silva Maciel ◽  
Henrique Igor Gomes Lira ◽  
Rodrigo Alves de Souza Galvão ◽  
...  
Keyword(s):  
Systemic Disease ◽  
Strong Association ◽  
Human Herpesvirus ◽  
Increased Risk ◽  
Immunodeficiency Virus ◽  
The Individual ◽  
Human Herpesviruses ◽  
Two Populations ◽  
Hiv Seropositive ◽  
Hsv 1

INTRODUCTION: Human herpesviruses are frequently associated with orofacial diseases in humans (HSV-1, EBV, CMV and HHV-8), some can also cause systemic disease (CMV and HHV-8). The transmission of these viruses occurs by contact with infected secretions, especially saliva. Human immunodeficiency virus infection is associated with an increased risk of HHVs and related diseases. METHODS: This work aimed to detect HSV-1, EBV, CMV and HHV-8 DNA in saliva of HIV-infected patients from Teresina, northeast Brazil, by PCR and compare these findings with age and sex matched HIV-seronegative individuals. RESULTS: No difference in prevalence was verified between HHV detection in the saliva of HIV-seropositive individuals and controls. The individual frequencies of these viruses in these two populations were different. HIV seropositivity correlated positively with the presence of CMV (OR: 18.2, p= 0.00032) and EBV (OR: 3.44, p= 0.0081). No association between CD4 counts and the prevalence of HHVs in the saliva was observed; however, a strong association was determined between seropositivity and the presence of multiple HHV DNAs in saliva (OR: 4.83, p = 0.0028). CONCLUSIONS: These findings suggest the asymptomatic salivary shedding of HHVs is a common event between HIV-seropositive and seronegative individuals from Teresina, Piauí, Brazil, and, especially for HIV-seropositive patients, saliva is a risk factor for the acquisition/transmission of multiple HHVs.

scholarly journals Interdigitated dynamic actin protrusions maintain stable cadherin adhesion

2020 ◽  
Author(s):  
John Xiao He Li ◽  
Vivian W. Tang ◽  
William M. Brieher
Keyword(s):  
Epithelial Cells ◽  
Actin Polymerization ◽  
Myosin Ii ◽  
Weak Binding ◽  
Pulling Forces ◽  
Strong Adhesion ◽  
Membrane Protrusions ◽  
Actin Protrusions

AbstractCadherins build stable, cohesive sheets of cells using paradoxically weak bonds. Actin is thought to convert weak binding into strong adhesion either by transmitting myosin dependent pulling forces to adhesive junctions or by clustering cadherins in the plane of the membrane. Here, however, we show that continuous actin polymerization stabilizes cadherin adhesion by directly driving membrane protrusions, not by promoting contractility or cadherin clustering. Lateral membranes of epithelial cells are continuously pushed against each another by protrusions. Micrometer sized cadherin puncta, long thought to be clusters of cadherins, turn out to be patches of microspikes interlocked by cadherin homophilic bonds to hold neighboring cells together. When actin polymerization is blocked, protrusions cease, puncta disappear, and lateral membranes detach from one another. In contrast, inhibiting myosin II contractility has no effect on adhesion.One Sentence SummaryStronger together: membrane interdigitations keep cells attached.

Iron alters glutamate secretion by regulating cytosolic aconitase activity

2005 ◽  
Vol 288 (5) ◽  
pp. C1117-C1124 ◽  
Author(s):  
M. Christine McGahan ◽  
Jill Harned ◽  
Marilyn Mukunnemkeril ◽  
Malgorzata Goralska ◽  
Lloyd Fleisher ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Retinal Pigment Epithelial ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Common Mechanism ◽  
Functional Link ◽  
Aconitase Activity ◽  
Pigment Epithelial ◽  
Glutamate Production ◽  
Pigment Epithelial Cells

Glutamate has many important physiological functions, including its role as a neurotransmitter in the retina and the central nervous system. We have made the novel observations that retinal pigment epithelial cells underlying and intimately interacting with the retina secrete glutamate and that this secretion is significantly affected by iron. In addition, iron increased secretion of glutamate in cultured lens and neuronal cells, indicating that this may be a common mechanism for the regulation of glutamate production in many cell types. The activity of the iron-dependent enzyme cytosolic aconitase (c-aconitase) is increased by iron. The conversion of citrate to isocitrate by c-aconitase is the first step in a three-step process leading to glutamate formation. In the present study, iron increased c-aconitase activity, and this increase was associated with an increase in glutamate secretion. Inhibition of c-aconitase by oxalomalate decreased glutamate secretion and completely inhibited the iron-induced increase in glutamate secretion. Derangements in both glutamate secretion and iron metabolism have been noted in neurological diseases and retinal degeneration. Our results are the first to provide a functional link between these two physiologically important substances by demonstrating a significant role for iron in the regulation of glutamate production and secretion in mammalian cells resulting from iron regulation of aconitase activity. Glutamatergic systems are found in many nonneuronal tissues. We provide the first evidence that, in addition to secreting glutamate, retinal pigment epithelial cells express the vesicular glutamate transporter VGLUT1 and that regulated vesicular release of glutamate from these cells can be inhibited by riluzole.

scholarly journals Association of cortactin with dynamic actin in lamellipodia and on endosomal vesicles

2000 ◽  
Vol 113 (24) ◽  
pp. 4421-4426 ◽  
Author(s):  
M. Kaksonen ◽  
H.B. Peng ◽  
H. Rauvala
Keyword(s):  
Actin Polymerization ◽  
Fluorescent Protein ◽  
Leading Edge ◽  
Time Lapse ◽  
Actin Binding ◽  
Common Mechanism ◽  
Membrane Protrusions ◽  
Green Fluorescent ◽  
Time Lapse Imaging ◽  
Endosomal Vesicles

We have used fluorescent protein tagging to study the localization and dynamics of the actin-binding protein cortactin in living NIH 3T3 fibroblast cells. Cortactin was localized to active lamellipodia and to small cytoplasmic spots. Time-lapse imaging revealed that these cortactin labeled structures were very dynamic. In the lamellipodia, cortactin labeled structures formed at the leading edge and then moved toward the cell center. Experiments with green fluorescent protein (GFP)-tagged actin showed that cortactin movement was coincident with the actin retrograde flow in the lamellipodia. Cytoplasmic cortactin spots also contained F-actin and were propelled by actin polymerization. Arp3, a component of the arp2/3 complex which is a key regulator of actin polymerization, co-localized with cortactin. Cytoplasmic cortactin-labeled spots were found to be associated with endosomal vesicles. Association was asymmetric and approximately half of the endosomes were associated with cortactin spots. Time-lapse imaging suggested that these cortactin and F-actin-containing spots propelled endosomes. Actin polymerization based propulsion may be a common mechanism for endomembrane trafficking in the same manner as used in the plasma membrane protrusions. As cortactin is known to interact with membrane-associated signaling proteins it could have a role in linking signaling complexes with dynamic actin on endosomes and in lamellipodia.

Enzymes of Human Herpesviruses

1992 ◽  
Vol 57 (8) ◽  
pp. 1577-1612 ◽  
Author(s):  
Pavel Kramata ◽  
Ivan Votruba
Keyword(s):  
Binding Protein ◽  
Human Herpesvirus ◽  
Dna Helicase ◽  
Point Of View ◽  
Uracil Dna Glycosylase ◽  
Replication Complex ◽  
Viral Genomes ◽  
Origin Binding Protein ◽  
Antiviral Chemotherapy ◽  
Human Herpesviruses

The properties of human herpesvirus-encoded enzymes are reviewed and the importance of sequence analysis of viral genomes as well as the experiments on characteristics of enzymes isolated from infected cell cultures are emphasized. The following enzymes are described in detail: DNA replication complex consisting of DNA polymerase, DNA helicase-primase, single-stranded DNA binding protein and origin binding protein, further thymidine kinase, ribonucleotide reductase, deoxyuridine triphosphatase as well as uracil-DNA-glycosylase, deoxyribonuclease and protein kinase. The importance of these enzymes from the point of view of antiviral chemotherapy is discussed.

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