A novel animal model of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in humanized mice.

EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a rare yet devastating disorder caused by EBV infection in humans. However, the mechanism of this disease has yet to be elucidated because of a lack of appropriate animal models. Here, we used a human CD34(+) cell-transplanted humanized mouse model and reproduced pathologic conditions resembling EBV-HLH in humans.

Dynamics of memory and naïve CD8+ T lymphocytes in humanized NOD/SCID/IL-2Rgammanull mice infected with CCR5-tropic HIV-1.

Creating a novel small animal model of HIV-1 infection that can support long-term systemic HIV-1 infection and produce HIV-1-specific immune response has a great benefit for studying HIV-1 pathogenesis in vivo. In the present study, we have generated a humanized mouse, NOG-hCD34 mouse, by transplanting newborn NOD/SCID/IL-2Rgamma(null) mice with human hematopoietic stem cells through hepatic injection. These mice were infected with a CCR5-tropic HIV-1 and were analyzed for plasma viral load, changes in peripheral blood T lymphocytes, and HIV-1-specific antibody production.

Selective infection of CD4+ effector memory T lymphocytes leads to preferential depletion of memory T lymphocytes in R5 HIV-1-infected humanized NOD/SCID/IL-2Rgammanull mice.

To investigate the events leading to the depletion of CD4(+) T lymphocytes during long-term infection of human immunodeficiency virus type 1 (HIV-1), we infected human CD34(+) cells-transplanted NOD/SCID/IL-2Rgamma(null) mice with CXCR4-tropic and CCR5-tropic HIV-1. CXCR4-tropic HIV-1-infected mice were quickly depleted of CD4(+) thymocytes and both CD45RA(+) naïve and CD45RA(-) memory CD4(+) T lymphocytes, while CCR5-tropic HIV-1-infected mice were preferentially depleted of CD45RA(-) memory CD4(+) T lymphocytes. Staining of HIV-1 p24 antigen revealed that CCR5-tropic HIV-1 preferentially infected effector memory T lymphocytes (T(EM)) rather than central memory T lymphocytes.