Inflammatory papillomatous hyperplasia and epidermal necrosis in a transgenic rat for HIV-1

J Dermatol Sci. 2009 Feb;53(2):112-9. doi: 10.1016/j.jdermsci.2008.08.015. Epub 2008 Nov 11.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / genetics
  • Cytokines / metabolism
  • Dermatitis / immunology
  • Dermatitis / pathology*
  • Dermatitis / virology
  • Disease Models, Animal
  • Epidermis / immunology
  • Epidermis / pathology*
  • Epidermis / virology
  • Erythema Multiforme / pathology
  • Erythema Multiforme / virology
  • Genotype
  • HIV Antibodies / blood
  • HIV Envelope Protein gp120 / genetics
  • HIV Envelope Protein gp120 / immunology
  • HIV Infections / complications*
  • HIV Infections / immunology
  • HIV Infections / pathology
  • HIV Infections / virology
  • HIV-1 / genetics*
  • HIV-1 / immunology
  • Hyperplasia
  • Necrosis
  • Phenotype
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Transgenic
  • Severity of Illness Index
  • Skin Ulcer / pathology
  • Skin Ulcer / virology
  • tat Gene Products, Human Immunodeficiency Virus / genetics

Substances

  • Cytokines
  • HIV Antibodies
  • HIV Envelope Protein gp120
  • RNA, Messenger
  • gp120 protein, Human immunodeficiency virus 1
  • tat Gene Products, Human Immunodeficiency Virus