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Use of In vivo Imaging to Monitor the Progression of Experimental Mouse Cytomegalovirus Infection in Neonates
Published on: July 6, 2013
Cytomegalovirus antivirals and development of improved animal models
Alistair McGregor1, K Yeon Choi
1University of Minnesota Medical School, Center for Infectious Diseases and Microbiology Translational Research, 2001 6th Street SE, MN 55455, USA. mcgre077@umn.edu
Introduction:
Cytomegalovirus (CMV) is a ubiquitous pathogen that establishes a lifelong asymptomatic infection in healthy individuals. Infection of immunesuppressed individuals causes serious illness. Transplant and AIDS patients are highly susceptible to CMV leading to life-threatening end-organ disease. Another vulnerable population is the developing fetus in utero, where congenital infection can result in surviving newborns with long-term developmental problems. There is no vaccine licensed for CMV and current antivirals suffer from complications associated with prolonged treatment. These include drug toxicity and emergence of resistant strains. There is an obvious need for new antivirals. Candidate intervention strategies are tested in controlled preclinical animal models but species specificity of human CMV precludes the direct study of the virus in an animal model.
Areas Covered:
This review explores the current status of CMV antivirals and development of new drugs. This includes the use of animal models and the development of new improved models such as humanized animal CMV and bioluminescent imaging of virus in animals in real time.
Expert Opinion:
Various new CMV antivirals are in development, some with greater spectrum of activity against other viruses. Although the greatest need is in the setting of transplant patients, there remains an unmet need for a safe antiviral strategy against congenital CMV. This is especially important as an effective CMV vaccine remains an elusive goal. In this regard, greater emphasis should be placed on suitable preclinical animal models and greater collaboration between industry and academia.
Insights
New antivirals are needed for cytomegalovirus (CMV) infections, especially for congenital CMV, as current treatments have limitations. Development of better preclinical animal models is crucial for advancing safe and effective therapies.
Area of Science:
- Virology
- Immunology
- Pharmacology
Background:
- Cytomegalovirus (CMV) establishes lifelong asymptomatic infections in healthy individuals but causes severe illness in immunocompromised populations, including transplant recipients, AIDS patients, and developing fetuses.
- Congenital CMV infection can lead to long-term developmental issues in newborns, highlighting a critical unmet medical need.
- Current antiviral therapies for CMV are limited by drug toxicity and the emergence of resistant strains, necessitating the development of novel therapeutic strategies.
Purpose of the Study:
- To review the current landscape of cytomegalovirus (CMV) antivirals and emerging drug development efforts.
- To explore the utility and advancements in animal models for studying CMV infection and evaluating potential interventions.
- To identify key areas for future research and development in CMV antiviral therapy.
Main Methods:
- Review of existing literature on CMV antiviral drugs and their limitations.
- Discussion of preclinical animal models used for CMV research, including limitations due to species specificity.
- Exploration of novel animal models, such as humanized animal CMV models and real-time bioluminescent imaging, to improve CMV research.
Main Results:
- Several new CMV antiviral agents are under development, with some exhibiting activity against other viruses.
- Existing animal models present challenges for studying human CMV due to species-specific differences.
- Advancements in animal models, including humanized models and in vivo imaging, offer improved platforms for preclinical evaluation.
Conclusions:
- There is a significant need for safe and effective antiviral strategies against CMV, particularly for congenital infections and in transplant patients.
- The development of improved preclinical animal models is essential for the successful advancement of new CMV therapies.
- Enhanced collaboration between academic institutions and the pharmaceutical industry is vital to accelerate the development of novel CMV interventions, especially given the lack of an effective CMV vaccine.
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