HIV-1 Tat enhances replicative potential of human oral keratinocytes harboring HPV-16 genome.
Introducing highly active antiretroviral therapy (HAART) has significantly decreased the morbidity and mortality in human immunodeficiency virus-positive (HIV+) individuals by decreasing the viral loads and increasing the CD4+ T-cell counts. Subsequently, the occurrence of many HIV-associated diseases has been dramatically declined except human papillomavirus (HPV)-associated lesions. Such notion suggests that immune response is not a major determinant, and that the direct interaction between HIV and HPV may be involved in the HPV-associated pathogenesis. In the current study, we investigated whether HIV plays a direct role in HPV-associated oral carcinogenesis by using HIV-1 transactivator protein (Tat), which is known to have oncogenic properties. We found that HIV-1 Tat not only increased the expression of HPV-16 E6 and E7 oncogenes in human oral keratinocytes harboring the HPV type-16 genome (HOK-16B), but also notably enhanced the proliferative capacity of the cells in vitro. Moreover, HOK-16B cells expressing HIV-1 Tat was capable of inducing cystic nodules in nude mice, while the control HOK-16B cells failed to produce nodules in the mice. Our results indicate that HIV could play a role in the HPV-associated pathogenesis by exerting oncogenic stimulus via Tat protein.
Kim
Reuben H
RH
UCLA School of Dentistry, Los Angeles, CA 90095-1668, USA.
Yochim
Ji Min
JM
Kang
Mo K
MK
Shin
Ki-Hyuk
KH
Christensen
Russell
R
Park
No-Hee
NH
D000818:Animals; D023241:Antiretroviral Therapy, Highly Active; D015967:Gene Expression Regulation, Viral; D015497:HIV-1 / Q000235:genetics*; D052162:Human papillomavirus 16 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000166:cytology* / Q000821:virology*; D051379:Mice; D008819:Mice, Nude; D009061:Mouth Mucosa / Q000166:cytology* / Q000821:virology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020079:Terminal Repeat Sequences; D014779:Virus Replication; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics* / Q000378:metabolism
D054322:tat Gene Products, Human Immunodeficiency Virus