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Inflammatory papillomatous hyperplasia and epidermal necrosis in a transgenic rat for HIV-1
Filiberto Cedeno-Laurent1, Joseph Bryant, Rita Fishelevich
1Division of Basic Science, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. fcedeno@fas.harvard.edu
Background:
Skin lesions commonly affect AIDS patients. The pathogenesis of certain dermatologic disorders primarily associated to HIV-1 is unclear, and better forms of therapy for these conditions need to be discovered. Transgenic animal models represent a novel approach for the study of these disorders and for the quest of more effective forms of treatment.
Objective:
Characterize this HIV-1 transgenic rat as a model to study skin diseases related to HIV/AIDS.
Methods:
A transgenic rat was developed, using an HIV-1 construct with deleted gag and pol genes. Morphological and genotypical evaluations were followed by cytokine profile characterization of the lesions.
Results:
We report the characterization of a colony of HIV-1 transgenic rats that developed skin lesions in a frequency of 22.5%. Cutaneous expression of functional HIV-1 transgenes correlated precisely with the severity of the phenotype. In early stages, rats manifested localized areas of xerosis and dispersed papulosquamous lesions. These hyperplastic manifestations were observed in conjunction with an increased epidermal expression of tat protein and a Th1/Th2 profile of cytokines. As the lesions progressed, they formed inflammatory plaques that subsequently ulcerated. Histologically, these lesions displayed a profound lymphocytic infiltrate, epidermal necrosis, and a marked increase of both Th1 and Th2 derived cytokines. Moreover, the presence of circulating IgG antibodies against HIV-1 gp120 was detected.
Conclusion:
This animal model as other HIV-1 transgenic mice described in the past, is not able to fully explain the myriad of skin findings that can occur in HIV-infected humans; however, it represents a potential animal model system for the study of immune-mediated inflammatory skin diseases.
Insights
A new HIV-1 transgenic rat model develops skin lesions, mimicking immune-mediated inflammatory skin diseases seen in AIDS patients. This model aids in studying HIV-related dermatologic conditions and therapies.
Area of Science:
- Immunology
- Dermatology
- Virology
Background:
- Skin lesions are common in patients with Acquired Immunodeficiency Syndrome (AIDS).
- The exact causes of HIV-1-associated skin disorders are not fully understood.
- Developing effective treatments for these conditions requires further research.
Purpose of the Study:
- To characterize a novel HIV-1 transgenic rat as a model for studying HIV/AIDS-related skin diseases.
- To investigate the potential of this model for therapeutic development.
Main Methods:
- Development of a transgenic rat using an HIV-1 construct with deleted gag and pol genes.
- Morphological and genotypical assessments of the rats.
- Cytokine profiling of induced skin lesions.
Main Results:
- A colony of HIV-1 transgenic rats exhibited skin lesions in 22.5% of cases.
- Cutaneous HIV-1 transgene expression correlated with lesion severity, progressing from xerosis to inflammatory plaques and ulceration.
- Lesions showed increased epidermal tat protein, a Th1/Th2 cytokine profile, lymphocytic infiltrate, epidermal necrosis, and antibodies against HIV-1 gp120.
Conclusions:
- This HIV-1 transgenic rat model shows promise for studying immune-mediated inflammatory skin diseases.
- While not fully replicating all human HIV-related skin findings, it offers a valuable system for research.
- Further investigation into this model could lead to improved therapies for HIV/AIDS dermatologic complications.
