Murine cytomegalovirus retinitis during retrovirus-induced immunodeficiency (MAIDS) in mice: interleukin-2 immunotherapy correlates with increased intraocular levels of perforin mRNA

Human cytomegalovirus (HCMV) generates a significant clinical burden worldwide, particularly among the immune compromised. In approximately 30% of untreated HIV/AIDS patients without access or sufficient response to antiretroviral therapies, for example, HCMV causes a sight-threatening retinitis. To study the mechanisms of AIDS-related HCMV retinitis, our lab has for many years used a mouse model in which a mixture of mouse retroviruses induces murine AIDS after approximately 10 weeks, rendering otherwise resistant mice susceptible to opportunistic pathogens. This immunodeficiency combined with subretinal inoculation of murine cytomegalovirus yields a reproducible model of the human disease, facilitating the discovery of many clinically relevant virologic and immunologic mechanisms of retinal destruction which we summarize in this review.

Download Full-text

Adoptive transfer of anti-cytomegalovirus effect of interleukin-2- activated bone marrow: potential application in transplantation

Blood ◽

10.1182/blood.v78.3.720.720 ◽

1991 ◽

Vol 78 (3) ◽

pp. 720-727 ◽

Cited By ~ 4

Author(s):

R Agah ◽

BS Charak ◽

V Chen ◽

A Mazumder

Keyword(s):

Bone Marrow ◽

Interleukin 2 ◽

Murine Cytomegalovirus ◽

Mcmv Infection ◽

Murine Bone Marrow ◽

Therapeutic Setting ◽

Infected Cells ◽

Novel Strategy

Abstract This work is a continuation of our studies that showed that interleukin- 2 (IL-2)-activated murine bone marrow (ABM) cells have potent cytotoxic potential against murine cytomegalovirus (MCMV)-infected targets in vitro, without loss of reconstitutive ability in vivo. Our data show that ABM cells lyse the MCMV-infected cells in vitro, at both acute and chronic stages of infection; this lysis is specific for the MCMV- infected cells. ABM cells supplemented with IL-2 therapy virtually eradicated the viral infection and prolonged the survival of MCMV- infected Balb/c mice, whether or not they were immunocompromised by irradiation (P less than .001 in both situations). Efficacy of ABM cells alone or IL-2 alone was less than the combination of ABM cells and IL-2. The efficacy of combination treatment with ABM cells and IL-2 in improving the survival of MCMV-infected mice was comparable, whether used in a preventive or a therapeutic setting. Therapy with ABM plus IL- 2 also prevented the reactivation of chronic MCMV infection after irradiation. Preliminary findings indicate that Thy-1+ and asialo GM1+ cells limited the MCMV proliferation by approximately 30% and 80%, respectively, while BM macrophages limited the proliferation of MCMV by 100%. These results suggest that BM transplantation (BMT) with ABM cells followed by IL-2 therapy may constitute a novel strategy to improve the host resistance against cytomegalovirus infection after BMT.

Download Full-text

Role of Bax in Death of Uninfected Retinal Cells During Murine Cytomegalovirus Retinitis

Investigative Opthalmology & Visual Science ◽

10.1167/iovs.14-15404 ◽

2014 ◽

Vol 55 (11) ◽

pp. 7137 ◽

Cited By ~ 3

Author(s):

Juan Mo ◽

Brendan Marshall ◽

Jason Covar ◽

Nancy Y. Zhang ◽

Sylvia B. Smith ◽

...

Keyword(s):

Cytomegalovirus Retinitis ◽

Murine Cytomegalovirus ◽

Retinal Cells

Download Full-text

Reduced frequency of murine cytomegalovirus retinitis in C57BL/6 mice correlates with low levels of suppressor of cytokine signaling (SOCS)1 and SOCS3 expression within the eye during corticosteroid-induced immunosuppression

Cytokine ◽

10.1016/j.cyto.2017.05.021 ◽

2017 ◽

Vol 97 ◽

pp. 38-41 ◽

Cited By ~ 5

Author(s):

Christine I. Alston ◽

Richard D. Dix

Keyword(s):

Cytomegalovirus Retinitis ◽

Murine Cytomegalovirus ◽

Cytokine Signaling ◽

Suppressor Of Cytokine Signaling ◽

Reduced Frequency ◽

Socs3 Expression ◽

Low Levels

Download Full-text

Adoptive transfer of anti-cytomegalovirus effect of interleukin-2- activated bone marrow: potential application in transplantation

Blood ◽

10.1182/blood.v78.3.720.bloodjournal783720 ◽

1991 ◽

Vol 78 (3) ◽

pp. 720-727

Author(s):

R Agah ◽

BS Charak ◽

V Chen ◽

A Mazumder

Keyword(s):

Bone Marrow ◽

Interleukin 2 ◽

Murine Cytomegalovirus ◽

Mcmv Infection ◽

Murine Bone Marrow ◽

Therapeutic Setting ◽

Infected Cells ◽

Novel Strategy

This work is a continuation of our studies that showed that interleukin- 2 (IL-2)-activated murine bone marrow (ABM) cells have potent cytotoxic potential against murine cytomegalovirus (MCMV)-infected targets in vitro, without loss of reconstitutive ability in vivo. Our data show that ABM cells lyse the MCMV-infected cells in vitro, at both acute and chronic stages of infection; this lysis is specific for the MCMV- infected cells. ABM cells supplemented with IL-2 therapy virtually eradicated the viral infection and prolonged the survival of MCMV- infected Balb/c mice, whether or not they were immunocompromised by irradiation (P less than .001 in both situations). Efficacy of ABM cells alone or IL-2 alone was less than the combination of ABM cells and IL-2. The efficacy of combination treatment with ABM cells and IL-2 in improving the survival of MCMV-infected mice was comparable, whether used in a preventive or a therapeutic setting. Therapy with ABM plus IL- 2 also prevented the reactivation of chronic MCMV infection after irradiation. Preliminary findings indicate that Thy-1+ and asialo GM1+ cells limited the MCMV proliferation by approximately 30% and 80%, respectively, while BM macrophages limited the proliferation of MCMV by 100%. These results suggest that BM transplantation (BMT) with ABM cells followed by IL-2 therapy may constitute a novel strategy to improve the host resistance against cytomegalovirus infection after BMT.

Download Full-text