scholarly journals Increased Cell-Mediated Immune Responses in Patients with Recurrent Herpes Simplex Virus Type 2 Meningitis

2011 ◽  
Vol 18 (4) ◽  
pp. 655-660 ◽  
Author(s):  
Elisabeth Franzen-Röhl ◽  
Danika Schepis ◽  
Maria Lagrelius ◽  
Kristina Franck ◽  
Petra Jones ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
T Cell ◽  
Dendritic Cell ◽  
Immune Responses ◽  
Herpes Simplex Virus Type ◽  
Nk Cell ◽  
Innate Immune ◽  
Simplex Virus

ABSTRACTThe clinical picture of herpes simplex virus type 2 (HSV-2) infection includes genital blisters and less frequently meningitis, and some individuals suffer from recurrent episodes of these manifestations. We hypothesized that adaptive and/or innate immune functional deficiencies may be a major contributing factor in susceptibility to recurrent HSV-2 meningitis. Ten patients with recurrent HSV-2 meningitis were studied during clinical remission. For comparison, 10 patients with recurrent genital HSV infections as well as 21 HSV-seropositive and 19 HSV-seronegative healthy blood donors were included. HSV-specific T cell blasting and cytokine secretion were evaluated in whole blood cultures. HSV-2-induced NK cell gamma interferon production, dendritic cell Toll-like receptor (TLR) expression, and TLR agonist-induced alpha interferon secretion were analyzed. Patients with recurrent HSV-2 meningitis had elevated T cell blasting and Th1 and Th2 cytokine production in response to HSV antigens compared to those of patients with recurrent genital infections. A somewhat increased NK cell response, increased dendritic cell expression of TLR3 and -9, and increased TLR-induced alpha interferon responses were also noted. Contrary to our expectation, recurrent HSV-2 meningitis patients have increased HSV-specific adaptive and innate immune responses, raising the possibility of immune-mediated pathology in the development of recurrent HSV2 meningitis.

scholarly journals DNA Vaccines Encoding Interleukin-8 and RANTES Enhance Antigen-Specific Th1-Type CD4+ T-Cell-Mediated Protective Immunity against Herpes Simplex Virus Type 2 In Vivo

2000 ◽  
Vol 74 (23) ◽  
pp. 11173-11180 ◽  
Author(s):  
Jeong-Im Sin ◽  
Jong J. Kim ◽  
Catherine Pachuk ◽  
C. Satishchandran ◽  
David B. Weiner
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
T Cell ◽  
Immune Responses ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Interleukin 8 ◽  
Simplex Virus

ABSTRACT Chemokines are inflammatory molecules that act primarily as chemoattractants and as activators of leukocytes. Their role in antigen-specific immune responses is of importance, but their role in disease protection is unknown. Recently it has been suggested that chemokines modulate immunity along more classical Th1 and Th2 phenotypes. However, no data currently exist in an infectious challenge model system. We analyzed the modulatory effects of selected chemokines (interleukin-8 [IL-8], gamma interferon-inducible protein 10 [IP-10], RANTES, monocyte chemotactic protein 1 [MCP-1], and macrophage inflammatory protein 1α [MIP-1α]) on immune phenotype and protection against lethal challenge with herpes simplex virus type 2 (HSV-2). We observed that coinjection with IL-8 and RANTES plasmid DNAs dramatically enhanced antigen-specific Th1 type cellular immune responses and protection from lethal HSV-2 challenge. This enhanced protection appears to be mediated by CD4+ T cells, as determined by in vitro and in vivo T-cell subset deletion. Thus, IL-8 and RANTES cDNAs used as DNA vaccine adjuvants drive antigen-specific Th1 type CD4+ T-cell responses, which result in reduced HSV-2-derived morbidity, as well as reduced mortality. However, coinjection with DNAs expressing MCP-1, IP-10, and MIP-1α increased mortality in the challenged mice. Chemokine DNA coinjection also modulated its own production as well as the production of cytokines. These studies demonstrate that chemokines can dominate and drive immune responses with defined phenotypes, playing an important role in the generation of protective antigen-specific immunity.

scholarly journals Herpes simplex virus type 2 virion host shutoff protein suppresses innate dsRNA antiviral pathways in human vaginal epithelial cells

2011 ◽  
Vol 92 (9) ◽  
pp. 1981-1993 ◽  
Author(s):  
Xiao-Dan Yao ◽  
Kenneth Lee Rosenthal
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Epithelial Cells ◽  
Herpes Simplex Virus Type ◽  
Innate Immune ◽  
Antiviral Responses ◽  
Virion Host Shutoff ◽  
Vaginal Epithelial Cells ◽  
Simplex Virus

Viruses that establish persistent infections have evolved numerous strategies to evade host innate antiviral responses. We functionally assessed the role of herpes simplex virus type 2 (HSV-2) virion host shutoff (vhs) protein on innate immune sensing pathways in human vaginal epithelial cells (VK2 ECs). Infection of cells with wild-type (WT) HSV-2 significantly decreased expression of innate immune sensors of viral infection, Toll-like receptor (TLR)2, TLR3, retinoic acid inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (Mda-5), relative to cells infected with a mutant that lacks vhs (vhsB) or mock-infected cells. Transfection with HSV-2 vhs similarly decreased expression of TLR2, TLR3, RIG-I and Mda-5, which was also confirmed in human embryonic kidney (HEK) 293 cells. vhsB infection of VK2 cells caused robust increases in the active form of interferon regulatory factor (IRF)3 and its translocation to the nucleus compared with the WT. Additionally, IRF3 activation by Sendai virus and polyinosinic : polycytidylic acid-induced stimulation of beta interferon (IFN-β) was significantly inhibited in vhs-transfected cells. Overall, our findings provide the first evidence that HSV-2 vhs plays roles in selectively inhibiting TLR3 and RIG-I/Mda-5, as well as TLR2-mediated antiviral pathways for sensing dsRNA and effectively suppresses IFN-β antiviral responses in human vaginal ECs.

Characterization of T-cell reactive epitopes in glycoprotein G of herpes simplex virus type 2 using synthetic peptides

2005 ◽  
Vol 150 (7) ◽  
pp. 1393-1406 ◽  
Author(s):  
L. Bellner ◽  
G.-B. Löwhagen ◽  
P. Tunbäck ◽  
I. Nordström ◽  
J.-Å. Liljeqvist ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
T Cell ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Synthetic Peptides ◽  
Glycoprotein G ◽  
Simplex Virus

scholarly journals CD4+ T-cell responses to herpes simplex virus type 2 (HSV-2) glycoprotein G are type specific and differ in symptomatic and asymptomatic HSV-2-infected individuals

2004 ◽  
Vol 85 (8) ◽  
pp. 2139-2147 ◽  
Author(s):  
Kristina Eriksson ◽  
Lars Bellner ◽  
Staffan Görander ◽  
Gun-Britt Löwhagen ◽  
Petra Tunbäck ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
T Cell ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Mononuclear Cells ◽  
Glycoprotein G ◽  
Simplex Virus ◽  
Hsv 1

T-cell recognition of the secreted and membrane-bound portions of the herpes simplex virus type 2 (HSV-2) glycoprotein G (sgG-2 and mgG-2, respectively) was compared in symptomatic and asymptomatic HSV-2-infected individuals and in HSV-2-seronegative controls and the responses with HSV-1 glycoproteins C and E (gC-1 and gE-1) were compared. CD4+ T cells from HSV-2-infected individuals specifically recognized both sgG-2 and mgG-2, whereas HSV-1-infected and HSV-seronegative controls did not respond to these glycoproteins. The responses to gC-1 and gE-1, on the other hand, were not type specific, as blood mononuclear cells from both HSV-1- and HSV-2-infected individuals responded in vitro. There was an association between the status of the infection (symptomatic versus asymptomatic) and the CD4+ T-cell responsiveness. Symptomatic HSV-2-seropositive individuals responded with significantly lower Th1 cytokine production to sgG-2 and mgG-2 than did asymptomatic HSV-2-infected carriers, especially within the HSV-1-negative cohort. No differences in T-cell proliferation were observed between asymptomatic and symptomatic individuals. The results have implications for studies of HSV-2-specific CD4+ T-cell reactivity in general and for analysis of immunological differences between asymptomatic and symptomatic individuals in particular.

scholarly journals In Vivo Modulation of Vaccine-Induced Immune Responses toward a Th1 Phenotype Increases Potency and Vaccine Effectiveness in a Herpes Simplex Virus Type 2 Mouse Model

1999 ◽  
Vol 73 (1) ◽  
pp. 501-509 ◽  
Author(s):  
Jeong-Im Sin ◽  
Jong J. Kim ◽  
Jean D. Boyer ◽  
Richard B. Ciccarelli ◽  
Terry J. Higgins ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Mouse Model ◽  
Immune Responses ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Model System ◽  
Cytokine Genes ◽  
Simplex Virus

ABSTRACT Several vaccines have been investigated experimentally in the herpes simplex virus type 2 (HSV-2) model system. While it is believed that CD4+-T-cell responses are important for protection in general, the correlates of protection from HSV-2 infection are still under investigation. Recently, the use of molecular adjuvants to drive vaccine responses induced by DNA vaccines has been reported in a number of experimental systems. We sought to take advantage of this immunization model to gain insight into the correlates of immune protection in the HSV-2 mouse model system and to further explore DNA vaccine technology. To investigate whether the Th1- or Th2-type immune responses are more important for protection from HSV-2 infection, we codelivered the DNA expression construct encoding the HSV-2 gD protein with the gene plasmids encoding the Th1-type (interleukin-2 [IL-2], IL-12, IL-15, and IL-18) and Th2-type (IL-4 and IL-10) cytokines in an effort to drive immunity induced by vaccination. We then analyzed the modulatory effects of the vaccine on the resulting immune phenotype and on the mortality and the morbidity of the immunized animals following a lethal challenge with HSV-2. We observed that Th1 cytokine gene coadministration not only enhanced the survival rate but also reduced the frequency and severity of herpetic lesions following intravaginal HSV challenge. On the other hand, coinjection with Th2 cytokine genes increased the rate of mortality and morbidity of the challenged mice. Moreover, of the Th1-type cytokine genes tested, IL-12 was a particularly potent adjuvant for the gD DNA vaccination.

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