CHROMOSOME-STUDIES IN HTLV-I, HTLV-II, AND HIV-1, HIV-2 CELL-LINES INFECTED IN-VIVO AND IN-VITRO

HTLV-I, II and HIV-1, 2 are T-cell tropic viruses, all belonging to th e retrovirus family. These viruses are transmitted horizontally by int imate contact or through blood products. The study of chromosomal chan ges in these T cells may enhance our understanding of the nature and m echanism of these viral infections. However, because of the cytopathic effect of these viruses on T cells, the direct observation of abnorma lities in these cells is sometimes difficult. We performed chromosomal analysis on six HTLV-I cell lines from patients with HTLV-I-positive leukemia/lymphoma, one HTLV-I variant cell line, and two HTLV-II-posit ive cell lines. The results of these studies were compared with the fi ndings in an earlier (published) study of direct preparations and shor t-term cultures of cells from 11 HTLV-I-positive NIH patients. Our stu dy also included cytogenetic analysis of seven established cell lines and six normal peripheral bloods infected in vitro with the HTLV-III(B ) strain of HIV-1 (five cell lines and six bloods) or HIV-2 (two lines ); all were studied both before and after viral infection. The results showed that all six HTLV-1 cell lines and the variant cell line had m ultiple chromosomal changes: three lines had deletions of chromosome 6 , with breakpoints between q21 and q25. Nine of the 11 NIH patients wi th HTLV-1 had clonal abnormalities, and six of these nine had chromoso me 6 deletions with breakpoints ranging from band q11 to band q23. The high incidence of 6q involvement may be of considerable significance in this clinical subgroup of HTLV-1 patients. The two HTLV-II cell lin es were established from patients suffering from HTLV-II infection. Bo th of these cell lines had translocations of chromosome 21 at p11, and both had extra copies of chromosome 20; no known oncogenes or recepto rs are located on these two chromosomes. Chromosome 17 was the chromos ome most frequently involved (three lines) in the five HIV-1-infected cell lines, followed by chromosomes 3 and 21; it is of interest that N GL (also known as C-ERBB2 or NEU oncogene), CD7 (a lymphocyte antigen) , HTLV-1 receptor, NGFR (nerve growth factor receptor), and MIC6 are a ll cell surface antigens coded by genes on chromosome 17q. No specific chromosome abnormalities were found in the normal blood samples infec ted with HIV-1, and no unique chromosome changes were noted in the two cell lines infected with HIV-2; however, the infected H9 line had a c hromosome 17 abnormality, a translocation involving band 17p11.