Human T-Cell Leukemia Virus Infection in Patients with Acquired Immune Deficiency Syndrome: Preliminary Observations

Recent evidence suggests that human T-cell leukemia virus (HTLV) infection occurs in patients with acquired immune deficiency syndrome (AIDS). HTLV has been isolated from peripheral blood T-lymphocytes from several patients with AIDS (1, 2), and a retrovirus, related to but clearly distinct from HTLV, has been isolated from cells from a lymph node of a patient with lymphadenopathy syndrome (LAS) (3), a syndrome that may precede AIDS itself. Also, HTLV nucleic acid sequences have been detected by nucleic acid hybridization in lymphocytes from two (6%) of 33 AIDS patients (4). In addition, antibodies to antigens expressed on the cell surface of HTLV-infected lymphocytes have been detected by an indirect immunofluorescent technique in sera from 19 (25%) of 75 AIDS patients (5), including patients with Kaposi's sarcoma alone (10/34), Pneumocystis carinii pneumonia alone (7/30), or patients with both diseases (2/11). Similar antibodies were detected in six (26%) of 23 patients with LAS. Such antibodies were rarely found in sera collected from homosexual men in New York City who served as controls during a case-control study in the fall of 1981 (1/81), homosexual men from whom sera were collected in 1978 during visits to a Chicago venereal disease clinic (0/118), and blood donors from a mid-Atlantic state who gave blood in 1977 but were unselected for sexual preference (1/137). Reported by Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health; Dept of Cancer Biology, Harvard School of Public Health; Department of Virology, Institut Pasteur, Paris; Div of Host Factors, Div of Viral Diseases, Div of Hepatitis and Viral Enteritis, AIDS Activity, Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: HTLV agents are retroviruses that have recently been associated with certain types of adult T-cell lymphoreticular neoplasms of man (6). HTLV-1 has been associated with acute T-cell leukemia and a related, but clearly different, viral agent, HTLV-2, with "hairy-cell" T-cell leukemia.

Retroviruses are ribonucleic acid (RNA) viruses containing the enzyme, reverse transcriptase, which allows production of a deoxyribonucleic acid (DNA) copy of their RNA genome. The DNA copy can then be integrated into the genome of the cell. Infections with retroviruses other than HTLV have been associated with a variety of neoplastic diseases in animals including chickens, cats, cattle and gibbons. The feline retrovirus also causes immune suppression.

HTLV agents are the only presently known retroviruses associated with human diseases. Clinically, however, the diseases previously associated with HTLV in endemic areas do not resemble AIDS. Infections are thought rarely to result in malignancies. HTLV may spread from some infected persons to their very close contacts, and concern has been expressed that it may be transmissible by blood or blood derivatives (7). HTLV infects and immortalizes* T-helper lymphocytes, and the virus can be isolated from infected patients by co-cultivation of their lymphocytes with uninfected human T-lymphocytes.

In the above studies, the reported low frequency of detecting HTLV sequences may reflect depletion of infected T-helper lymphocytes, since patients initially positive for such sequences have had negative tests several months later (4).

HTLV-infected cells express specific virus structural and virus-induced cellular proteins. Antibodies reactive with these virus-specific proteins are moderately prevalent (12% of blood donors) in residents of southwest Japan, an area with a relatively high prevalence of adult T-cell leukemia, and in residents of some Caribbean Islands (4% of St. Vincent blood donors); they have rarely been found in healthy Americans or western Europeans, although these population groups have not been studied extensively.

While the above serologic findings associate AIDS with antibody to HTLV-specific cell surface-associated antigens, such antibodies were identified in only about one quarter of the AIDS patients tested. This relatively low frequency of antibody in AIDS patients might represent a lack of test sensitivity, too stringent criteria for positive tests, infection of AIDS patients with an agent related to but not identical with HTLV, nonspecific polyclonal B-cell responses, inability of many AIDS patients to mount antibody responses to these antigens, collection of sera from patients at improper times during disease evolution, or combinations of these and other yet-to-be identified factors. Alternatively, HTLV or an HTLV-like agent might simply represent yet another opportunistic agent in these multiply infected AIDS patients.

Further study is required to determine if any etiologic relationship exists between HTLV and AIDS.

References

1. Gallo RC, Savin PS, Gelmann EP, et al. Isolation of human T-cell leukemia virus in acquired immune-deficiency syndrone. Science, (in press).

2. Gallo RC. Unpublished data.

3. Barre-Senoussi F, Chermann JC, Rey F, et al. Isolation of a T-lymphotropic retrovirus from a patient at risk of acquired immunodeficiency syndrome. Science, (in press).

4. Gelmann EP, Popovic M, Blayney D, et al. Proviral DNA of a retrovirus human T-cell leukemia virus, in two patients with AIDS. Science, (in press).

5. Essex M, McLane MF, Lee TH, et al. Antibodies to human T-cell leukemia virus-associated cell membrane antigens (HTLV-MA) in patients with acquired immune deficiency (AIDS). Science, (in press).

6. Reitz MS Jr, Kalyanaraman VS, Robert-Guroff M, et al. Human T-cell leukemia/lymphoma virus: the retrovirus of adult T-cell leukemia/lymphoma. J Infect Dis 1983;147:399-405.

7. Weiss D, Blattner W, Hahn B, Greaves M. Worries about infectious cancer. Nature 1983;302:567.

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