scholarly journals Reactive oxygen species drive herpes simplex virus (HSV)-1-induced proinflammatory cytokine production by murine microglia

2011 ◽  
Vol 8 (1) ◽  
pp. 123 ◽  
Author(s):  
Shuxian Hu ◽  
Wen S Sheng ◽  
Scott J Schachtele ◽  
James R Lokensgard
2007 ◽  
Vol 82 (2) ◽  
pp. 617-629 ◽  
Author(s):  
Martine Aubert ◽  
Zheng Chen ◽  
Robin Lang ◽  
Chung H. Dang ◽  
Carla Fowler ◽  
...  

ABSTRACT The Us5 gene of herpes simplex virus (HSV) encodes glycoprotein J (gJ). The only previously reported function of gJ was its ability to inhibit apoptosis. However, the mechanism by which gJ prevents apoptosis is not understood, and it is not known whether gJ mediates additional cellular effects. In this study, we evaluated the expression, localization, and cellular effects of Us5/gJ. Us5 was first expressed 4 h after infection. gJ was detectable at 6 h and was expressed in glycosylated and unglycosylated forms. Us5 was regulated as a late gene, with partial dependency on DNA replication for expression. Us5 expression was delayed in the absence of ICP22; furthermore, expression of Us5 in trans protected cells from apoptosis induced by an HSV mutant with deletion of ICP27, suggesting that the antiapoptotic effects of ICP22 and ICP27 are mediated in part through effects on gJ expression. Within HSV-infected or Us5-transfected cells, gJ was distributed widely, especially to the endoplasmic reticulum, trans-Golgi network, and early endosomes. gJ interacted with FoF1 ATP synthase subunit 6 by a yeast two-hybrid screen and had strong antiapoptotic effects, which were mediated by protein rather than mRNA. Antiapoptotic activity required the extracellular and transmembrane domains of gJ, but not the intracellular domain. Consistent with inhibition of FoF1 ATP synthase function, Us5 was required for HSV-induced reactive oxygen species (ROS) formation, and gJ was sufficient to induce ROS in Us5-transfected cells. Thus, HSV gJ is a multifunctional protein, modulating other cellular processes in addition to inhibition of apoptosis.


Author(s):  
Tae In Kim ◽  
Eun-Bin Kwon ◽  
You-Chang Oh ◽  
Younghoon Go ◽  
Jang-Gi Choi

Herpes simplex virus type 1 (HSV-1) is ubiquitous in many populations despite the use of acyclovir or related nucleoside analogs for treating infection. Drug resistance impairs the treatment of HSV-infected individuals who have immune deficits, underscoring the need for new safe and effective antiviral agents. Mori ramulus (the young twig of Morus alba L.) has long been used to treat diseases in Korea, Japan, and China. Recent studies have reported multiple pharmacological activities of Mori ramulus and its constituent morusin, but their effects on HSV-1 remain unknown. Here, we found that treatment with Mori ramulus ethanol extract (MRE) significantly reduced the replication of fluorescently labeled HSV-1 in Vero cells and inhibited the expression of HSV-1 envelope glycoprotein D (gD) and tegument protein VP16. MRE, furthermore, blocked HSV-1-induced production of reactive oxygen species (ROS), and this mediated the inhibition of viral replication. We identified morusin as the active antiviral component of MRE and found that morusin post-treatment was sufficient to inhibit viral gD and VP16 in addition to HSV-1-induced ROS production. Therefore, the inhibition of HSV-1-induced ROS may explain the antiviral activity of MRE against HSV-1. MRE or its component morusin may be potentially developed for anti-HSV-1 agents.


2011 ◽  
Vol 208 (3) ◽  
pp. 417-420 ◽  
Author(s):  
Edwina Naik ◽  
Vishva M. Dixit

High levels of reactive oxygen species (ROS) are observed in chronic human diseases such as neurodegeneration, Crohn’s disease, and cancer. In addition to the presence of oxidative stress, these diseases are also characterized by deregulated inflammatory responses, including but not limited to proinflammatory cytokine production. New work exploring the mechanisms linking ROS and inflammation find that ROS derived from mitochondria act as signal-transducing molecules that provoke the up-regulation of inflammatory cytokine subsets via distinct molecular pathways.


2008 ◽  
Vol 53 (1) ◽  
pp. 73-83 ◽  
Author(s):  
V. Ďurmanová ◽  
M. Sapák ◽  
J. Košovský ◽  
I. Režuchová ◽  
M. Kúdelová ◽  
...  

1994 ◽  
Vol 8 (3) ◽  
pp. 218-223 ◽  
Author(s):  
Shinichiro Yasumoto ◽  
Yoichi Moroi ◽  
Tetsuya Koga ◽  
Ikuo Kawamura ◽  
Masao Mitsuyama ◽  
...  

2021 ◽  
Vol 23 (4) ◽  
pp. 767-774
Author(s):  
G. I. Krichevskaya ◽  
E. S. Sorozhkina ◽  
N. V. Balatskaya ◽  
I. G. Kulikova ◽  
A. E. Andryushin ◽  
...  

Behcet’s disease (BD) is a systemic autoinflammatory-autoimmune disease (chronic systemic vasculitis) of unknown etiology, almost 70% of patients develop uveitis. BD pathogenesis is complex, human herpesviruses (HHV) play an important role among infectious trigger factors. Ability of herpesviruses to modulate cytokine production and evade host’s immune response is known.Aim of the study was to assess the effect of Herpes simplex virus type 1, Herpes simplex virus type 2, Cytomegalovirus, Epstein-Barr virus on systemic levels of chemokines, pro- and anti-inflammatory cytokines in BD with and without uveitis. Serum samples were collected from 116 BD patients chronically infected with HHV and examined in ELISA-test for markers of HHV reactivation (IgG-antibodies to immediate early HSV antigens 1, 2 and CMV, early EBV antigen). Concentration of IL-1β, IFNγ, MCP-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-12p70, IL-13, IL-18, TNFα, GMCSF, Eotaxin, GRO-α, IP-10, MIP-1α, MIP-1β, SDF-1α, RANTES detected in multiplex analysis. TGF-β1, TGF-β2 were measured in ELISA-test. Depending on presence and activity of uveitis 3 groups of patients with BD were identified: group 1 – active uveitis, group 2 – remission of uveitis, group 3 – BD without ocular manifestations. After serological study 2 subgroups were highlighted in each group: a) patients with antibody markers of reactivation of at least one HHV, b) patients chronically infected with HHV, without serological signs of reactivation. Mean level and detection rate of cytokines and chemokines in patients with active uveitis (1a, 1b) and in remission (2a, 2b) were compared with patients without eye damage (3a, 3b). Chronic HHV infection (subgroup “b”) was compared with reactivation (subgroup “a”). A significant increase of MCP-1/ CCL2, MIP-1α/CCL3, MIP-1β/CCL4, RANTES/CCL5, IP-10, SDF-1α chemokines in serum, as well as IFNγ, TGF-β1, and TGF-β2 was observed in patients with uveitis (regardless of their activity) and HHV reactivation compared to patients without uveitis. Our data indicate that systemic production of cytokines and chemokines in BD patients and uveitis could be affected by the activity of chronic herpesvirus infections, and the greatest changes are related to chemokines. 


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