title: Inflammatory papillomatous hyperplasia and epidermal necrosis in a transgenic rat for HIV-1.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Basic Science, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. fcedeno@fas.harvard.edu
authors.forename: Filiberto
authors.initials: F
authors.lastname: Cedeno-Laurent
authors.forename: Joseph
authors.initials: J
authors.lastname: Bryant
authors.forename: Rita
authors.initials: R
authors.lastname: Fishelevich
authors.forename: Odell D
authors.initials: OD
authors.lastname: Jones
authors.forename: April
authors.initials: A
authors.lastname: Deng
authors.forename: Maria L
authors.initials: ML
authors.lastname: Eng
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Gaspari
authors.forename: J Roberto
authors.initials: JR
authors.lastname: Trujillo
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003872:Dermatitis / Q000276:immunology / Q000473:pathology* / Q000821:virology; D004195:Disease Models, Animal; D004817:Epidermis / Q000276:immunology / Q000473:pathology* / Q000821:virology; D004892:Erythema Multiforme / Q000473:pathology / Q000821:virology; D005838:Genotype; D015483:HIV Antibodies / Q000097:blood; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000150:complications* / Q000276:immunology / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D006965:Hyperplasia; D009336:Necrosis; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D055647:Rats, Transgenic; D012720:Severity of Illness Index; D012883:Skin Ulcer / Q000473:pathology / Q000821:virology; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D016207:Cytokines; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D012333:RNA, Messenger; C514793:gp120 protein, Human immunodeficiency virus 1; D054322:tat Gene Products, Human Immunodeficiency Virus