Several isolates of a human type-C retrovirus belonging to one group, known as human T-cell leukemia virus (HTLV), have previously been obtained from patients with adult T-cell leukemia or lymphoma. The T-cell tropism of HTLV and its prevalence in the Caribbean basin prompted a search for it in patients with the epidemic T-cell immune deficiency disorder known as AIDS. Peripheral blood lymphocytes from one patient in the United States and two in France were cultured with T-cell growth factor (TCGF) an shown to express HTLV antigens. Virus from the U.S. patient was isolated and characterized and shown to be related to HTLV subgroup I. The virus was also transmitted into normal human T cells from umbilical cord blood of a newborn. Whether or not HTLV-I or other retroviruses of this family with T-cell tropism cause AIDS, it is possible that patients from whom the virus can be isolated can also transmit it to others. If the target cell of AIDS is the mature T cell as suspected, the methods used in these studies may prove useful for the long-term growth of these cells and for the identification of antigens specific for the etiological agent of AIDS.

Several isolates of human T-cell leukemia/lymphoma virus (HTLV) were transmitted to normal human T cells obtained from the umbilical cord blood of newborns. T cells from seven specimens were immortalized by infection with different HTLV isolates and their properties were compared with those of' activated uninfected normal T cells grown in the presence of Tcell growth factor (TCGF) and with those of HTLV-positive neoplastic T-cell lines derived from patients with T-cell malignancies. The HTLV-infected cells generally belonged to a class of mature T cells (OKT4' and Leu 3A+) and differed from the normal uninfected cells in that they could be propagated in culture indefinitely; possessed altered morphology, including convoluted nuclei and some bi-and multinucleated giant cells; formed large clumps in culture; demonstrated' a diminished requirement for TCGF; had an increased density of TCGF receptors; often became completely independent of exogenous TCGF; and expressed HLA-DR determinants. These properties of the HTLV-infected cord blood T cells contrasted to those of uncultured cord blood T cells and of cord blood cells stimulated with mitogen-and grown with TCGF but resembled the characteristics of T-cell lines established previously from patients with HTLV-associated T-cell malignancies. This in vitro system offers a-unique opportunity to study the basic mechanism involved in abnormal growth and neoplastic transformation of a specific class of human T cells.The discovery of T-cell growth factor (TCGF) in 1976 (1) enabled the development of the-technology to grow normal and neoplastic mature T cells in vitro for considerable periods of time (2). Using purified TCGF (3), it was possible to grow in culture T cells that exhibited several characteristics of the primary tumor cells from patients with mature T-cell malignancies (2). A type C retrovirus designated human T-cell leukemia/ lymphoma virus (HTLV) was isolated from,some neoplastic Tcell lines (4-7). Detailed characterization of these isolates showed that HTLV is an exogenous human retrovirus closely linked to a subtype of mature T-cell malignancy and distinct from all-known animal retroviruses (8-15). In our laboratory 15 HTLV isolates have been obtained from people of different parts of the world (4-7). In addition, human retrovirus isolates have been inde-., pendently reported by workers in other laboratories (16)(17)(18) and comparative studies have shown that the new isolates are members of the HTLV group (19).HTLV infection of normal T cells can induce long-term growth of the infected cells (16,20). One source of HTLV, the MT-2 cell line, was derived from umbilical cord blood T cells designed to -be a "feeder cell" for growing leukemia T cells in a cocultivation experiment, but the cord blood T cells incidentally became immortalized by an apparent infection with HTLV derived from the leukemia cells (16). Yamamoto et al. (21) recently confirmed this observation by using a MT-2 isolate for infection of human lymphocytes. We have transmitted numerou...

A retrospective study was conducted on 134 HIV-infected females evaluated at an HIV/AIDS centre in south India to characterize their sociodemographics, HIV risk factors and initial clinical presentations. The mean age was 29 years; 81% were housewives; 95% were currently or previously married; 89% reported heterosexual sex as their only HIV risk factor; and 88% reported a history of monogamy. The majority were of reproductive age, thus the potential for vertical transmission of HIV and devastating impacts on families is alarming. Nearly half of these women initially presented asymptomatically implying that partner recruitment can enable early HIV detection. Single partner heterosexual sex with their husband was the only HIV risk factor for the majority of women. HIV prevention and intervention strategies need to focus on married, monogamous Indian women whose self-perception of HIV risk may be low, but whose risk is inextricably linked to the behaviour of their husbands.

The possibility ofusing oligodeoxynucleotides complementary to viral RNA or proviral DNA to inhibit the replication of human T-cell lymphotropic virus type III (HTLV-Ill) [the etiological agent of acquired imnunodeficiency syndrome (AIDS)] in cultured human cells was addressed by studying the association of 32P-labeled oligodeoxynucleotides with mammalian cellular components. The results indicated that exogenous oligodeoxynudeotides at 20 pM became associated with the membrane/cytosol fractions of the cell in amounts approximating 1.5 pM. Oligodeoynudeotides complementary to a region close to the tRNAL9 primer binding site on HTLV-M RNA and others complementary to HTLV-I mRNA donor or acceptor splice sites inhibited viral replication (assayed as reverse transcriptase) and gene expression (assayed as virus-encoded proteins p15 and p24) by as much as 95%. Use of control (random) oligodeoxynudeotides suggests that the antiviral effects were specific. Although these esults pertain to HTLV-I-infected cells in tissue culture, rather than to AIDS patients, they nevertheless point to a therapeutic potential of the complementary oligodeoxynudeotide ("hybridization competition" or "hybridon") approach in the treatment of patients with AIDS and AIDS-related complex.

Type-C RNA tumor viruses have been implicated in the etiology of naturally occurring leukemias and lymphomas of animals. Human T-cell leukemia/lymphoma virus (HTLV) is the first human virus of this class consistently identified in association with a specific type of human leukemia/lymphoma. The isolation of HTLV was made possible by the ability to grow mature T-cells in tissue culture usually with T-cell growth factor (TCGF). We now report a cluster of adult T-cell leukemia/lymphoma among Blacks from the Caribbean in which all eight cases are positive for HTLV virus and/or antibody. These patients have disease that appears indistinguishable from Japanese adult T-cell leukemia/lymphoma which, as we have also reported, is associated with HTLV in over 90% of cases. The finding of HTLV antibodies in some of the normal population in the Caribbean and Japan, and the clustering of a specific form of T-cell leukemia/lymphoma in these virus-endemic areas, suggest that HTLV infection may be associated with the occurrence of a distinctive clinico-pathologic entity.

Modified oligodeoxynucleotides complementary to RNA of human immunodeficiency virus 1 (HIV-1) were tested for their ability to inhibit virally induced syncytium formation and expression of viral p24 protein. The Fig. 1. All the modified oligonucleotides were found to be resistant to nucleases such as snake venom or spleen phosphodiesterases. amounts of material for toxicity studies were made by a manual solid-support method on an Omnifit assembly (13). Unmodified oligomers were made and purified by methods described previously (2). Phosphorothioates and phosphoramidates were synthesized by a modification of the Hphosphonate procedure (14,15). To generate phosphorothioate linkages, oxidation following the final coupling and detritylation was replaced by treatment with 0.1 M sulfur in carbon disulfide/triethylamine (9:1, vol/vol) at room temperature for up to 2 hr, depending on chain length (16). For the phosphoramidates, this step was replaced by treatment with a 10% solution of the appropriate amine in carbon tetrachloride for up to 1.5 hr, depending on chain length (16).After deblocking in concentrated ammonium hydroxide (550C for 51/2 hr or room temperature for >2 days), products were purified on 2-mm-thick preparative layer plates (Merck silica gel 60) in propanol/water/concentrated ammonium hydroxide (55:35:10, vol/vol). Phosphorothioates were further purified on DEAE-cellulose and C18 silica (details will be published elsewhere). Phosphoramidates from preparative layer plates were passed through Sephadex G-25 in aqueous 30% (vol/vol) ethanol and then through C18 silica and dialyzed. In all cases, small amounts of oligomers attached to the solid support were taken before the final treatment with sulfur or amine and were oxidized with 2% iodine in pyridine/water (98:2, vol/vol) (15) to phosphodiesters. These were used for determination of base composition by enzymatic degradation to nucleosides followed by HPLC. The phosphorothioates were also characterized by polyacrylamide gel electrophoresis, where they had similar mobility to the corresponding diesters.Phosphoramidates were further characterized by hydrolysis with formic acid to the phosphodiesters (16) for comparison with authentic samples on HPLC and degradation to nucleosides for determination of nucleoside composition and integrity by HPLC. A useful indicator of oligonucleotide purity and integrity is the melting curve of its duplex with a complementary DNA Abbreviations: HIV, human immunodeficiency virus; AIDS, acquired immunodeficiency syndrome. 7079The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

A family of oligonucleotides and phosphorothioate oligonucleotide analogues was synthesized with a cholesteryl group tethered at the 3'-terminal internucleoside link. This modification, introduced to enhance interaction of the polyanions with cell membranes, significantly increases the antiviral activity of the oligomers, as judged by inhibition of syncytia formation and expression of viral proteins p17, p24, and reverse transcriptase for human immunodeficiency virus 1 in Molt-3 cells. In the most favorable case, with a 20-mer cholesteryl-phosphorothioate derivative, complete inhibition by all assays was obtained with an oligomer concentration of 0.2 jIM. Even decamers were active, and some antiviral activity was observed for a heptanucleotide cholesteryl-phosphorothioate derivative, which binds very poorly to complementary oligonucleotides. These facts, and the finding that the activity of the phosphorothioate decamers does not correlate with a specific sequence., suggests that a mechanism other than "antisense inhibition" may be operative in these systems.

authors request that the following correction be noted. In both papers, the statement that toxicity studies in mice were performed using compound at a concentration of 640 ,ug/ml is incorrect. In all cases, various concentrations of oligodeoxynucleotides were in a volume of 1 ml of pyrogenfree distilled water.