scholarly journals Age-Dependent Role for CCR5 in Antiviral Host Defense against Herpes Simplex Virus Type 2

2005 ◽  
Vol 79 (15) ◽  
pp. 9831-9841 ◽  
Author(s):  
Nina Ank ◽  
Klavs Petersen ◽  
Lene Malmgaard ◽  
Søren C. Mogensen ◽  
Søren R. Paludan
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Cytotoxic Activity ◽  
Nk Cells ◽  
Host Defense ◽  
Herpes Simplex Virus Type ◽  
Wild Type ◽  
Age Dependent ◽  
Simplex Virus

ABSTRACT Elimination of viral infections is dependent on rapid recruitment and activation of leukocytes with antiviral activities to infected areas. Chemokines constitute a class of cytokines that have regulatory effects on leukocyte migration and activity. In this study we have studied the role of CC chemokine receptor 1 (CCR1) and CCR5 in host defense during a generalized herpes simplex virus type 2 (HSV-2) infection. Whereas both 4- and 8-week-old CCR1−/− mice resembled wild-type mice (C57BL/6) with respect to defense against the infection, significantly higher virus titers were seen in the livers and brains of 4-week-old CCR5−/− mice. At the age of 8 weeks, CCR5−/− were indistinguishable from wild-type mice and cleared the infection from liver and spleen. Although 4-week-old CCR5−/− mice were able to recruit natural killer (NK) cells to the site of infection, these cells had reduced cytotoxic activity compared to NK cells from wild-type mice. This was not due to lower production of alpha/beta interferon or interleukin-12, two well-described activators of cytotoxic activity in NK cells. We also noted that the spleens of young CCR5−/− mice did not increase in size during infection as did the spleens of wild-type and CCR1−/− mice. This observation was accompanied by impaired proliferation of CCR5−/− splenocytes (SCs) ex vivo. Moreover, migration of CD8+ T cells to the liver in response to infection was impaired in CCR5−/− mice, and adoptive transfer of SCs from CCR5−/− mice infected for 6 days into newly infected wild-type mice did not improve antiviral activity in the liver, in contrast to what was seen in mice receiving immune SCs from wild-type mice. Altogether, this study shows that CCR5 plays an age-dependent role in host defense against HSV-2 by supporting both the innate and adaptive immune response.

scholarly journals B7 Costimulation Plays an Important Role in Protection from Herpes Simplex Virus Type 2-Mediated Pathology

2002 ◽  
Vol 76 (5) ◽  
pp. 2563-2566 ◽  
Author(s):  
Lydia G. Thebeau ◽  
Lynda A. Morrison
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Immune Responses ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Mortality Rates ◽  
Neurologic Disease ◽  
Wild Type ◽  
Simplex Virus

ABSTRACT We have used mice lacking both B7-1 and B7-2 costimulation molecules (B7KO) to investigate the effects of B7 costimulation on herpes simplex virus type 2 (HSV-2) pathogenesis. B7KO mice infected intravaginally with virulent HSV-2 showed more severe genital and neurologic disease and higher mortality rates than their wild-type counterparts. These results suggest that B7 costimulation molecules play an important role in the development of primary immune responses protective against HSV-2.

scholarly journals Clearance of Herpes Simplex Virus Type 2 by CD8+ T Cells Requires Gamma Interferon and either Perforin- or Fas-Mediated Cytolytic Mechanisms

2005 ◽  
Vol 79 (23) ◽  
pp. 14546-14554 ◽  
Author(s):  
Melanie E. Dobbs ◽  
Jane E. Strasser ◽  
Chin-Fun Chu ◽  
Claudia Chalk ◽  
Gregg N. Milligan
Keyword(s):  
T Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Gamma Interferon ◽  
Wild Type ◽  
Ifn Γ ◽  
Simplex Virus

ABSTRACT The T-cell-mediated resolution of herpes simplex virus type 2 (HSV-2) genital infections is not fully understood. In these studies, the mechanisms by which CD8+ T cells clear virus from the genital epithelium were examined. Ovalbumin (OVA)-specific CD8+ T cells from OT-I transgenic mice cleared a thymidine kinase-deficient, ovalbumin-expressing HSV-2 virus (HSV-2 tk− OVA) from the genital epithelium of recipient mice, and clearance was abrogated by in vivo neutralization of gamma interferon (IFN-γ). Further, CD8+ OT-I T cells deficient in IFN-γ were unable to clear HSV-2 tk− OVA from the vaginal epithelium. The requirement for cytolytic mechanisms in HSV-2 tk− OVA clearance was tested in radiation chimeras by adoptive transfer of wild-type or perforin-deficient OT-I T cells to irradiated Fas-defective or wild-type recipients. Although a dramatic decrease in viral load was observed early after challenge with HSV-2 tk− OVA, full resolution of the infection was not achieved in recipients lacking both perforin- and Fas-mediated cytolytic pathways. These results suggest that IFN-γ was responsible for an early rapid decrease in HSV-2 virus titer. However, either perforin- or Fas-mediated cytolytic mechanisms were required to achieve complete clearance of HSV-2 from the genital epithelium.

scholarly journals Mucosal Immunity to Herpes Simplex Virus Type 2 Infection in the Mouse Vagina Is Impaired by In Vivo Depletion of T Lymphocytes

1998 ◽  
Vol 72 (4) ◽  
pp. 2677-2685 ◽  
Author(s):  
Margaret B. Parr ◽  
Earl L. Parr
Keyword(s):  
T Cells ◽  
Monoclonal Antibodies ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Herpes Simplex Virus Type ◽  
Wild Type ◽  
Neurological Illness ◽  
Simplex Virus

ABSTRACT Intravaginal (IVAG) inoculation of wild-type herpes simplex virus type 2 (HSV-2) in mice causes epithelial infection followed by lethal neurological illness, while IVAG inoculation of attenuated HSV-2 causes epithelial infection followed by development of protective immunity against subsequent IVAG challenge with wild-type virus. The role of T cells in this immunity was studied by in vivo depletion of these cells with monoclonal antibodies. Three groups of mice were used for each experiment: nonimmune/challenged mice, immune/challenged mice, and immune depleted mice [immune mice depleted of a T-cell subset(s) shortly before challenge with HSV-2]. Mice were assessed for epithelial infection 24 h after challenge, virus protein in the vaginal lumen 3 days after challenge, and neurological illness 8 to 14 days after challenge. Monoclonal antibodies to CD4, CD8, or Thy-1 markedly reduced T cells in blood, spleen, and vagina, but major histocompatibility complex class II antigens were still partially upregulated in the vaginal epithelium after virus challenge, indicating that virus-specific memory T-cell function was not entirely eliminated from the vagina. Nevertheless, immune mice depleted of CD4+and CD8+ T cells, Thy-1+ T cells, or CD8+ T cells alone had greater viral infection in the vaginal epithelium than nondepleted immune mice, indicating that T cells contribute to immunity against vaginal HSV-2 infection. All immune depleted mice retained substantial immunity to epithelial infection and were immune to neurological illness, suggesting that other immune mechanisms such as virus-specific antibody may also contribute to immunity.

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