A retrovirus HTLV-3 has recently been implicated in the etiology of the Acquired Immunodeficiency Syndrome. This virus is tropic for the T4 subset of lymphocytes, but only in their activated form, and it is cytotoxic for them. Sustained infection of normal peripheral blood lymphocytes by the virus in vitro is, therefore, difficult to achieve. It is the purpose of this research project to test whether sustained infection by HTLV-3 in vivo, and progression from asymptomatic infection to the AIDS related complex or to fully established AIDS, generally requires help, i.e., a cofactor in the form of the presence of a population of B cells infected by the Epstein-Barr virus (EBV). The hypothesis is that with loss of T4 cells by HTLV-3 infection, a temporary immunodeficient state may ensue characterized not only by loss of the population of T cells susceptible to HTLV, but also by unrestrained growth of EBC infected B lymphocytes. The infected B cells would then provide a needed secondary cell population for proliferation of the HTLV-3 virus, as has been described by Montagnier, and also an effective number of EBC-infected B cells for creating newly activated, and thus newly susceptible, T4 cells. Our hypothesis will be tested by 1) evaluating immunocompetence by lymphokine and cytotoxic cell production after EBV infection in vitro; 2) measuring the quantity of the EBV-infected B lymphocytes from the circulation or in biopsy to tissues; 3) searching for dual infection by EBV and HTLV-3 in cloned lymphoblastoid cell lines from the patients; 4) determining whether these conditions occur in reciprocal relation to each other and whether this occurs at times of asymptomatic infection by HTLV-3 or at later prodromal stages of the disease; and 5) assessing in a long term prospectus follow-up whether these measurements predict progression towards end stage disease. These studies will be carried out in a carefully documented university hospital patient population. The specific documentation of these immunologic abnormalities in relation to disease progression will have important implications in developing optimal therapeutic modalities.
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