We developed multiple immune defect mice either backcrossing of scid mutation onto the other mutant mice such as beige, nude, Dh, and NOD or knocking out gene responsive to lymphoid function such as recombination of the activating gene 2 (RAG-2). 6 new congenic BALB/cA-bg-scid,NOD/Shi-scid, BALB/cA-Dh-scid, BALB/cA-nu-scid, BALB/cA-RAG2% and C57BL/6-RAG2 % were generated. Human T lymphocytes were reconstituted in a new immunnodeficiency mouse strain. We found 6 new immunodeficient mouse strains which efficiently received human PBL engraft and human immunodeficiency virus type I (HIV-1) was inoculated into these hu-PBL-immunodeficient mice. Among the hu-PBL-immunodeficient strain, we could reproduce the high levels of HIV-1 viremia comparable to or more significant levels than that in HIV-1 primary infection. Systemic HIV-1 infection including lung, liver, lymph nodes, spleen, and brain was demonstrated by quantitative DNA or RNA-PCR technique. The amounts of gag p24 in plasma from the HIV- 1 infected mice reached to 250 ng/ml and end-point-dilution method indicated more than 10(6) tissue-culture-infectious dose (TCID)/ml, which is about 1000 fold higher viral load than that in HIV-1 infected conventional hu-PBL-C.B-17 scid mouse. These results indicate that our hu-PBL-NOD-scid animal is useful for studies of activation mechanism in HIV-1 replication in vivo and primary infection.

Animal DNA, Viral/METABOLISM Disease Models, Animal HIV Infections/BLOOD/*VIROLOGY HIV-1/GENETICS/*ISOLATION & PURIF/PHYSIOLOGY Mice Mice, Inbred BALB C Mice, Inbred NOD Mice, SCID Polymerase Chain Reaction RNA, Viral/METABOLISM *Viremia Virus Replication ABSTRACT

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