Preferential HIV-1 integration sites in macrophages and HIV-associated malignancies.
HIV-infected individuals are at risk for developing certain types of cancers. While there are data to show that non-random HIV integration may occur, our goal was to identify preferential genomic sites where HIV integration might be targeted leading to oncogenesis. Initially, a linker-primer PCR strategy was used to identify HIV integration in isolated macrophages. Inverse-PCR was then used to analyze specimens from patients diagnosed with HIV-associated malignancies. From isolated macrophages, integration near a toll-like receptor on chromosome 4 was found. Necropsy tissues from 11 cases were analyzed with 1 tumor specimen found to have HIV integrated in chromosome 22q13.2 and within 300 kb of HSCBCIP1 (CAP-binding protein complex interacting homologue). Tumor-specific primers were then used to screen uninvolved tissue from the same patient, which did not amplify the site-specific region. This report demonstrates that in both an in vitro system and human malignant tissue, specific viral integration can be identified.
Killebrew
D A
DA
Retrovirology Research Laboratory, Hawaii AIDS Clinical Research Program, Department of Biomedical Sciences, John A Burns School of Medicine, University of Hawaii, Honolulu, HI 96816, USA. dak@hawaii.edu
Troelstrup
D
D
Shiramizu
B
B
D001483:Base Sequence; D002478:Cells, Cultured; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D015658:HIV Infections / Q000150:complications*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008264:Macrophages / Q000821:virology*; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000737:chemistry / Q000235:genetics / Q000821:virology*; D016662:Virus Integration / Q000235:genetics*
D004279:DNA, Viral