Testing therapeutic interventions in pre-clinical hepatitis B virus, HIV and tuberculosis infection
We have developed several unique modifications to generate human immune system (HIS)-reconstituted mice that allow an unprecedented ability to modulate genetic pathways during the course of HIV infection.
HIS mice are animals that have been transplanted with human haemopoietic stem cells capable of recapitulating the human haemopoietic system, particularly the human lymphoid compartment. Additionally we have engineered the animals to express the human IL-7 cytokine at levels that maintain physiological proportions of T cells, B cells and myeloid cells. Prior to transplantation the human haemopoietic stem cells can be transduced with genetic vectors that permit reversible silencing of genes in vivo.
Using this system we can analyse the human immune response to HIV and the virological consequences that follow the transient silencing of human immune cell signalling pathways. Similar preclinical in vivo infection models allow us to examine the role of genes that regulate immunity to HBV and MTb infection.
