Tissue specific HPV expression and downregulation of local immune responses in condylomas from HIV seropositive individuals.
OBJECTIVE
To study the effect of tissue specific human papillomavirus (HPV) expression and its effect on local immunity in condylomas from HIV positive individuals.


METHODS
Biopsy specimens of eight penile and eight perianal condylomas from HIV seropositive individuals were analysed. Expression of viral genes (HIV-tat and HPV E7 and L1) was determined by RT-PCR. The status of local immunity also was determined by RT-PCR by measuring CD4, CD8, CD16, CD1a, HLA-DR, and HLA-B7 mRNA levels in the tissues. Differentiation was determined by measuring involucrin, keratinocyte transglutaminase, as well as cytokeratins 10, 16, and 17. Proliferation markers such as PCNA and c-myc were also determined.


RESULTS
The transcription pattern of HPV in perianal condylomas, which preferentially expressed the early (E7) gene, was different from that of penile condylomas, which primarily expressed the late (L1) gene. This transcription pattern is in good correlation with the keratinisation and differentiation patterns of the two epithelia: perianal biopsies preferentially expressed K16 and K17 while penile warts mainly expressed K10, markers of parakeratotic and orthokeratotic epithelia, respectively. Perianal biopsies also showed a higher degree of proliferation (PCNA and c-myc). Interestingly, transcription of HIV-tat was also higher in perianal than in penile biopsies. A high degree of local immunodeficiency was observed in perianal biopsies--that is, levels of CD4, CD16, and CD1a mRNAs were significantly lower. A negative correlation between CD1a (Langerhans cells) levels and HPV E7 levels was established. HPV E7 levels positively correlated with HIV-tat levels. Perianal tissues demonstrated more CD1a depression and tat associated HPV upregulation.


CONCLUSIONS
HIV influences the expression of HPV genes resulting in local immunosuppression that might lead to an inappropriate immune surveillance of viral infection. Also, tissue type is an important factor in controlling viral transcription in a differentiation dependent manner. These findings may explain the higher rate of dysplasia and neoplasia in the perianal area.
Arany
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Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston 77555, USA.
Evans
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T
Tyring
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D000917:Antibody Formation; D001004:Anus Diseases / Q000276:immunology* / Q000821:virology; D003218:Condylomata Acuminata / Q000276:immunology* / Q000821:virology; D015696:Gene Products, tat / Q000276:immunology; D005814:Genes, Viral / Q000276:immunology; D006679:HIV Seropositivity / Q000276:immunology* / Q000821:virology; D006801:Humans; D008297:Male; D009856:Oncogene Proteins, Viral / Q000276:immunology; D027383:Papillomaviridae / Q000235:genetics; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000276:immunology*; D010409:Penile Diseases / Q000276:immunology* / Q000821:virology; D012333:RNA, Messenger / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012333:RNA, Messenger; C059731:oncogene protein E7, Human papillomavirus type 16; D054322:tat Gene Products, Human Immunodeficiency Virus