Mechanisms of AIDS-related cytomegalovirus retinitis

2019 ◽  
Vol 14 (8) ◽  
pp. 545-560 ◽  
Author(s):  
Jessica Carter ◽  
Christine I Alston ◽  
Jay Oh ◽  
Lauren-Ashley Duncan ◽  
Judee Grace Esquibel Nemeno ◽  
...  
Keyword(s):  
Mouse Model ◽  
Human Cytomegalovirus ◽  
Human Disease ◽  
Cytomegalovirus Retinitis ◽  
Murine Cytomegalovirus ◽  
Opportunistic Pathogens ◽  
Aids Patients ◽  
Clinical Burden ◽  
Antiretroviral Therapies ◽  
Murine Aids

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.

scholarly journals In Vivo Competence of Murine Cytomegalovirus under the Control of the Human Cytomegalovirus Major Immediate-Early Enhancer in the Establishment of Latency and Reactivation

2008 ◽  
Vol 82 (20) ◽  
pp. 10302-10307 ◽  
Author(s):  
Montse Gustems ◽  
Andreas Busche ◽  
Martin Messerle ◽  
Peter Ghazal ◽  
Ana Angulo
Keyword(s):  
Animal Model ◽  
Mouse Model ◽  
Human Cytomegalovirus ◽  
Pivotal Role ◽  
Immediate Early ◽  
Murine Cytomegalovirus ◽  
Direct Test ◽  
Cmv Infection ◽  
Physiological Functions

ABSTRACT The human cytomegalovirus (HCMV) major immediate-early enhancer has been postulated to play a pivotal role in the control of latency and reactivation. However, the absence of an animal model has obstructed a direct test of this hypothesis. Here we report on the establishment of an in vivo, experimentally tractable system for quantitatively investigating physiological functions of the HCMV enhancer. Using a neonate BALB/c mouse model, we show that a chimeric murine CMV under the control of the HCMV enhancer is competent in vivo, replicating in key organs of mice with acute CMV infection and exhibiting latency/reactivation features comparable for the most part to those of the parental and revertant viruses.

Role of human cytomegalovirus genotype polymorphisms in AIDS patients with cytomegalovirus retinitis

2012 ◽  
Vol 202 (1) ◽  
pp. 37-47 ◽  
Author(s):  
Jens-Uwe Vogel ◽  
Jürgen Otte ◽  
Frank Koch ◽  
Hermann Gümbel ◽  
Hans Wilhelm Doerr ◽  
...  
Keyword(s):  
Human Cytomegalovirus ◽  
Cytomegalovirus Retinitis ◽  
Aids Patients

scholarly journals A Mouse Model That Mimics AIDS-Related Cytomegalovirus Retinitis: Insights into Pathogenesis

Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 850
Author(s):  
Jay J. Oh ◽  
Jessica J. Carter ◽  
Richard D. Dix
Keyword(s):  
Mouse Model ◽  
Mouse Models ◽  
Vision Loss ◽  
Opportunistic Infections ◽  
Retinal Disease ◽  
Cytomegalovirus Retinitis ◽  
Murine Cytomegalovirus ◽  
Virus Infections ◽  
Tissue Destruction ◽  
Immunodeficiency Syndrome

With the appearance of the worldwide AIDS pandemic four decades ago came a number of debilitating opportunistic infections in patients immunosuppressed by the pathogenic human retrovirus HIV. Among these was a severe sight-threatening retinal disease caused by human cytomegalovirus (HCMV) that remains today a significant cause of vision loss and blindness in untreated AIDS patients without access or sufficient response to combination antiretroviral therapy. Early investigations of AIDS-related HCMV retinitis quickly characterized its hallmark clinical features and unique histopathologic presentation but did not begin to identify the precise virologic and immunologic events that allow the onset and development of this retinal disease during HIV-induced immunosuppression. Toward this end, several mouse models of experimental cytomegalovirus retinitis have been developed to provide new insights into the pathophysiology of HCMV retinitis during AIDS. Herein, we provide a summary and comparison of these mouse models of AIDS-related HCMV retinitis with particular emphasis on one mouse model developed in our laboratory in which mice with a murine acquired immunodeficiency syndrome (MAIDS) of murine retrovirus origin develops a reproducible and well characterized retinitis following intraocular infection with murine cytomegalovirus (MCMV). The MAIDS model of MCMV retinitis has advanced the discovery of many clinically relevant virologic and immunologic mechanisms of virus-induced retinal tissue destruction that are discussed and summarized in this review. These findings may extend to the pathogenesis of AIDS-related HCMV retinitis and other AIDS-related opportunistic virus infections.

Detection of Human Cytomegalovirus Retinitis and Monitoring of Ganciclovir Treatment Using Conjunctival Swab with Polymerase Chain Reaction in AIDS Patients

2000 ◽  
Vol 11 (2) ◽  
pp. 85-91
Author(s):  
S H Chiou ◽  
J H Liu ◽  
W W Wong ◽  
Y J Chan ◽  
Y C Chang ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Human Cytomegalovirus ◽  
Predictive Value ◽  
Cytomegalovirus Retinitis ◽  
Chain Reaction ◽  
Aids Patients ◽  
Conjunctival Swab ◽  
Patients At Risk ◽  
Polymerase Chain ◽  
Sensitivity Specificity

This report studies the accuracy of conjunctival swab polymerase chain reaction (CS-PCR) for the diagnosis of human cytomegalovirus retinitis (HCMV) in AIDS patients. PCR and virus culture were used for the detection of HCMV in conjunctival swab, serum, and urine specimens from 38 AIDS patients between April 1996 and April 1998. The clinical utility of the identification of HCMV retinitis by these 6 different methods was demonstrated by their prediction power to estimate AIDS patients at risk of contracting HCMV retinitis. The sensitivity, specificity, positive predictive value, and negative predictive value of CS-PCR for the detection of HCMV retinitis were 91.5%, 80.9%, 60.8%, and 92.7%, respectively; for serum PCR were 74.3%, 81.7%, 57.2%, and 90.3%; for urine PCR were 100%, 17.3%, 20.4%, and 100%; for conjunctival swab culture were 22.7%, 100%, 100%, and 86%; for serum culture were 27.3%, 98.1%, 75%, and 86.4%; and for urine culture were 90.9%, 44.2%, 25.6%, and 95.8%.

scholarly journals A Review of Murine Cytomegalovirus as a Model for Human Cytomegalovirus Disease—Do Mice Lie?

2020 ◽  
Vol 22 (1) ◽  
pp. 214
Author(s):  
Michelle A. Fisher ◽  
Megan L. Lloyd
Keyword(s):  
Human Cytomegalovirus ◽  
Murine Cytomegalovirus ◽  
Clinical Samples ◽  
Mouse Strains ◽  
Cytomegalovirus Disease ◽  
Wild Mice ◽  
Congenital Cytomegalovirus ◽  
Non Invasive ◽  
Species Specific ◽  
Disseminated Disease

Since murine cytomegalovirus (MCMV) was first described in 1954, it has been used to model human cytomegalovirus (HCMV) diseases. MCMV is a natural pathogen of mice that is present in wild mice populations and has been associated with diseases such as myocarditis. The species-specific nature of HCMV restricts most research to cell culture-based studies or to the investigation of non-invasive clinical samples, which may not be ideal for the study of disseminated disease. Initial MCMV research used a salivary gland-propagated virus administered via different routes of inoculation into a variety of mouse strains. This revealed that the genetic background of the laboratory mice affected the severity of disease and altered the extent of subsequent pathology. The advent of genetically modified mice and viruses has allowed new aspects of disease to be modeled and the opportunistic nature of HCMV infection to be confirmed. This review describes the different ways that MCMV has been used to model HCMV diseases and explores the continuing difficulty faced by researchers attempting to model HCMV congenital cytomegalovirus disease using the mouse model.

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