Background: Nullbasic (NB) is a derivative of the HIV-1 transcriptional activator protein, Tat. We have shown that with a stable expression in cells, NB inhibits HIV replication in Jurkat cells and primary CD4+ cells. It also inhibits HIV reactivation from latently infected cell lines. This project is to establish a mouse model using transplanted CD4+ cells to test the anti-HIV properties of NB in vivo.
Method: Human CD4+ cells expressing NB ZsGreen1 (NBZsG) or ZsGreen1 (ZsG) were either infected with HIV for two days or kept as uninfected. Five million uninfected CD4-NBZsG or CD4-ZsG cells, 8 million HIV infected CD4-NBZsG cells or 9 million HIV infected CD4-ZsG cells were injected intravenously to NOD-SCID mice (8-9 week old). Blood samples were collected for measuring HIV replication and monitoring CD4+ cell population.
Results: CD4+ cells were detected in blood on day 3 and peak levels were measured between days 10 -14. In HIV infected CD4-ZsG mice, the peripheral blood human CD45+ cell population decreased from > 65.8% to <5.9% from days 10 to 21. HIV mRNA was detected in plasma samples from HIV infected ZsG mice by day 7 and increased more than 100-fold by day 21. No HIV mRNA was detected in plasma samples from HIV infected CD4-NBZsG mice and uninfected CD4-NBZsG and CD4-ZsG mice. Large amounts of human CD45+ cells were present in lung, liver and spleen in NBZsG mice, while in HIV infected ZsG mice, CD45+ cells were greatly reduced in all organ samples. The HIV mRNA level in CD4-NBZsG mice was decreased by more than 53-fold in lung compared to ZsG mice.
Conclusion: A mouse model for testing anti-HIV activities of NBZsG in vivo has been established. Our preliminary data showed that NBZsG protected CD4+ cells from HIV replication in vivo.