scholarly journals Early Resolution of Herpes Simplex Virus Type 2 Infection of the Murine Genital Tract Involves Stimulation of Genital Parenchymal Cells by Gamma Interferon

2006 ◽  
Vol 81 (1) ◽  
pp. 423-426 ◽  
Author(s):  
Melanie D. Bird ◽  
Chin-Fun Chu ◽  
Alison J. Johnson ◽  
Gregg N. Milligan
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Herpes Simplex Virus Type ◽  
Genital Tract ◽  
Virus Clearance ◽  
Ifn Γ ◽  
Simplex Virus ◽  
Parenchymal Cells ◽  
Stimulation Of

ABSTRACT Early clearance of a thymidine kinase-deficient strain of herpes simplex virus type 2 from the female genital tract required T-cell-produced gamma interferon (IFN-γ). Transfer of activated CD8+ T cells to irradiated C57BL/6 mice resulted in rapid virus clearance, but clearance was greatly delayed in recipients deficient in the IFN-γ receptor (IFN-γR). Early virus clearance was demonstrated in radiation chimeras in which IFN-γR expression was limited to parenchymal cells, but resolution was significantly delayed in chimeras deficient in IFN-γR expression and chimeras expressing IFN-γR only on hematopoietic cells. Together, these results suggest that early IFN-γ-mediated protection was manifested mainly by stimulation of genital parenchymal cells.

scholarly journals Differential roles of B cells and IFN-γ-secreting CD4+ T cells in innate and adaptive immune control of genital herpes simplex virus type 2 infection in mice

2001 ◽  
Vol 82 (4) ◽  
pp. 845-853 ◽  
Author(s):  
Ali M. Harandi ◽  
Bo Svennerholm ◽  
Jan Holmgren ◽  
Kristina Eriksson
Keyword(s):  
T Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
T Cell ◽  
B Cells ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Ifn Γ ◽  
Simplex Virus

The role of B, CD4+ T and CD8+ T cells in both primary genital infection with attenuated herpes simplex virus type 2 (HSV-2) and development of protective immunity to a later challenge with virulent HSV-2 using lymphocyte-deficient mice has been elucidated. Following primary inoculation with attenuated thymidine kinase-deficient (TK−) HSV-2, B cell-deficient (μMT) mice developed a local viraemia and transient genital inflammation, suggesting a role for B cells in the innate control of local infection and inflammation. Natural antibodies are implicated in this process, as passive transfer of normal serum into μMT mice significantly reduced HSV-2 TK− shedding in the vaginal lumen, although it did not affect subsequent inflammation. Protection against lethal HSV-2 challenge was noted in HSV-2-vaccinated wild-type, CD8+ T cell-deficient and μMT mice and was characterized by strong virus-specific IFN-γ responses in vitro and delayed type hypersensitivity (DTH) responses in vivo. In contrast, CD4+ T cell-deficient (CD4−/−) mice had impaired HSV-2-specific IFN-γ production and DTH responses and succumbed rapidly to genital HSV-2 challenge. However, protective responses to HSV-2 could be induced in HSV-2-vaccinated CD4−/− mice by treatment with recombinant IFN-γ. Taken together, these results suggest that CD4+ T cells secreting IFN-γ are critical for immune protection against lethal genital HSV-2 re-infection, whereas B cells/natural antibodies have anti-viral and -inflammatory effects in the innate control of a primary infection.

scholarly journals Herpes simplex virus type 2 induces secretion of IL-12 by macrophages through a mechanism involving NF-κB

2000 ◽  
Vol 81 (12) ◽  
pp. 3011-3020 ◽  
Author(s):  
Lene Malmgaard ◽  
Søren R. Paludan ◽  
Søren C. Mogensen ◽  
Svend Ellermann-Eriksen
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Neutralizing Antibodies ◽  
Parasitic Infections ◽  
Virus Infectivity ◽  
Ifn Γ ◽  
Simplex Virus

Interleukin (IL)-12 is an important proinflammatory and immunoregulatory cytokine expressed primarily by macrophages. Although IL-12 appears to be essential for clearance of many bacterial and parasitic infections, only little is known about the production and regulation of this cytokine during viral infections. In this study we have shown that infection of mouse macrophages with herpes simplex virus type 2 (HSV-2) induces secretion of the p40 subunit of IL-12, and this induction was synergistically enhanced by interferon (IFN)-γ. The production of IL-12 p40 was accompanied by production of bioactive IL-12 p70, since HSV-2-induced IFN-γ secretion was blocked by neutralizing antibodies against IL-12. The IL-12-inducing effect of HSV-2 was abrogated when virus infectivity was destroyed by heat or UV irradiation, indicating that a functional viral genome is required and that interaction of viral glycoproteins with cellular receptors is not sufficient. Production of IL-12 p40 was transcriptionally regulated and required de novo protein synthesis. Although IFN-α, IL-1β and tumour necrosis factor-α marginally influenced IL-12 production, they did not seem to constitute the endogenous factor(s) responsible for the effect of the virus infection. HSV-2 infection induced nuclear-binding activity to the κB halfsite of the IL-12 p40 promoter, and inhibitors of nuclear factor (NF)-κB activation significantly reduced IL-12 p40 production in infected cells. Collectively our data show that HSV-2 infection of murine macrophages induces production of IL-12 through a mechanism requiring intermediary synthesis of viral or host proteins and involving activation of NF-κB.

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