U937-SCID MOUSE XENOGRAFTS - A NEW MODEL FOR ACUTE IN-VIVO HIV-1 INFECTION SUITABLE TO TEST ANTIVIRAL STRATEGIES

In this study we attempted to develop a new xenochimeric model for HIV infection in SCID mice, characterized by an easy engraftment of targe t cells, high levels of viremia and long-lasting HIV-1 infection. SCID mice were injected subcutaneously with uninfected human U937 cells an d cell-free HIV-1 (IIIB strain) or HIV-1-infected human peripheral blo od lymphocytes (PBL). Mice were evaluated for tumor growth, viral infe ction at the tumor level (DNA-polymerase chain reaction (PCR), RNA-PCR ) and immunostaining for the p55/p18 HIV protein) and p24 antigenemia or serum HIV-1 RNA copies. Pretreatment of mice with antibodies to eit her mouse-IFN alp or granulocytes resulted in a tumor take and levels of p24 antigenemia higher than in control mice. In mice treated with t hese antibody preparations, there was a long-lasting HIV infection wit h the presence of high levels of circulating infectious virus (serum p 24 values up to 4000 pg/ml and serum RNA copies up to 5 x 10(7)/ml ove r 3 months, with the majority of the cells expressing HIV-antigens at the tumor site). Intraperitoneal treatment of SCID mice with AZT (480 mg/kg per day) resulted in a complete inhibition of both p24 and RNA H IV-1 copies in the serum, together with a marked reduction in the numb er of infected cells and the levels of virus expression at the tumor s ite. We conclude that some specific features of this model (i.e. easy establishment, high reproducibility, well defined kinetics of virus in fection, massive and long persistent viremia) underline the special ad vantages of its use for testing new antiviral therapies. (C) 1997 Else vier Science B.V.