Modeling HIV infection and therapies in humanized mice

Abstract

The human immunodeficiency virus (HIV) type-1 is a human-specific virus. The lack of a widely available small-animal model has seriously hampered HIV research. In 2004, a new humanised mouse model was reported. It was based on the intrahepatic injection of human CD34+ cord blood cells into newborn, highly immunodeficient mice. These mice develop a lymphoid system of human origin and are highly susceptible to HIV infection and showed disseminated infection, persistent viraemia and characteristic helper CD4+ T-cell loss. Here, we will briefly review the various existing humanised mouse models and highlight their value to the study of HIV infection.

The HIV-1 transgenic rat model of neuroHIV

“…A second approach was to genetically engineer rodents so that their cells express the human version of the CD4 receptor and the chemokine co-receptors to which HIV-1 binds to enter target cells (Nischang, Gers-Huber et al 2012). The envelope glycoprotein 120 (gp120) on the surface of the HIV-1 virus interacts with target cell receptors to begin the cell entry process.…”

HIV pre-exposure prophylaxis: Mucosal tissue drug distribution of RT inhibitor Tenofovir and entry inhibitor Maraviroc in a humanized mouse model

“…The hu-HSC humanized mouse model such as RAG-hu employs engraftment of human hematopoietic stem cells (HSC) into newborn immunodeficient (Rag1 −/− or Rag2 −/− γc −/− ) mice whereas the BLT mouse model is derived by transplantation of human fetal thymus tissue, liver tissue and HSC (Akkina, 2013; Denton and Garcia, 2011). Both models harbor human immune cells in mucosal sites such as vaginal and rectal tissue, and are susceptible to HIV infection via these routes thus mimicking key aspects of viral mucosal transmission (Berges et al, 2008; Denton and Garcia, 2012; Nischang et al, 2012). Both topical and systemic PrEP strategies employing ARVs have been successfully tested using these models (Chateau et al, 2013; Denton et al, 2011; Neff et al, 2011; Neff et al, 2010).…”

Lentivector Knockdown of CCR5 in Hematopoietic Stem and Progenitor Cells Confers Functional and Persistent HIV-1 Resistance in Humanized Mice

“…Humanized (hu) mice, which are generated by the transplantation of CD34 ϩ cells, are of particular value in this context. These mice excel in their multilineage hematopoiesis (10), are highly permissive to HIV (11), and allow for the gene engineering of human CD34 ϩ cells before transplantation (12). Indeed, various anti-HIV moieties have been investigated in hu mice as gene therapy options, including cellular factors, boosting the anti-HIV immune response, and the HIV genome itself (12).…”