A Simple Mouse Model for the Study of Human Immunodeficiency Virus

Abstract

The purpose of this paper is to select a model for HIV that uses few parameters while fitting the world prevalence and death data well. Here we consider a set of models based on Erlang's method of stages, including some with and some without social distancing. The use of stages is supported by biological studies which suggest that HIV passes through stages in each individual, although the exact number is not known. This set of models can represent such stages using a successive number of classes. To perform model selection, we compute R 0 and use it to estimate initial values of the parameters in this model. We run thousands of iterations of a Nelder-Mead simplex search algorithm to determine the optimal values of parameters for each model and the error associated with each model. These errors are used to compute AIC c values and then the AIC c values are compared to select the most likely model. The selected model from this experiment contains the social distancing term as well as four infected classes/stages. We then perform identifiability analysis and determine that the "true values" of the parameters for this model are uniquely determinable based on the data points.

Moving beyond the mousetrap: current and emerging humanized mouse and rat models for investigating prevention and cure strategies against HIV infection and associated pathologies

“…Human CD4 + T cells are the major target for HIV infection; thus, a mouse model with human CD4 + T cells provides a platform for modeling HIV/AIDS. Various immunodeficient mouse models lacking mature T, B, [8] and NK cells, along with defects in macrophage phagocytic function [9] support robust reconstitution of human CD4+ T cells and other lymphocytes (e.g. CD8 + T cells) following transplantation of human PBMCs or CD4+ T cells.…”

“…Alternatively, to generate human immune cell only, PBMCs, CD4+ T cells, or CD34 + HSCs are transplanted via IV or IP injection. (III) Transplanted mice are maintained under specific pathogen-free conditions and the human lymphoid tissue(s), and/or immune cell reconstitution in the peripheral blood and murine lymphoid tissues (humanized-murine tissues) are allowed to develop over a period of 2-10 weeks (or more), resulting in the HIS-humanized mouse model at 4 weeks post-transplantation [9,10], hence providing a humanized mouse model that can be generated in a relatively short period. The PBL-humanized mouse model supports HIV replication and provides a means of evaluating the efficacy of direct-acting therapeutics (e.g.…”

“…The PBL-humanized mouse model supports HIV replication and provides a means of evaluating the efficacy of direct-acting therapeutics (e.g. antivirals drugs, antibodies) geared towards preventing HIV transmission [11] and controlling HIV replication [9]. Additionally, PBL-humanized mouse models constructed using PBMCs from HIV-infected individuals with undetectable viral load can be employed as an in vivo assay (mouse-quantitative viral outgrowth assay) for evaluating the eradication of the HIV reservoir in said individuals [12,13].…”

“…A major limitation of this model is the rapid development of graft-versus-host (GvHD) disease within 6-7 weeks following transplantation of lymphocytes, thus significantly restricting the experimental window [14]. Additionally, the PBL-humanized mouse model does not incorporate human macrophages, which are a major HIV reservoir in various organs, including the brain [9,15]. However, modification of the PBL-humanized mouse model via transplantation of HIV-infected monocyte-derived macrophages in the brain supports HIV infection and pathogenesis in the brain [15].…”

“…The HSC-humanized mouse model supports HIV infection, CD4+ T cell depletion, chronic immune activation and limited anti-HIV T and B cell immune responses [4]. A major advantage of the HSC-humanized mouse model over the PBL-humanized mouse model is the delayed and reduced incidence of GvHD, which provides the opportunity for long-term modeling of HIV infection and replication [9]. The HSC-humanized mouse model provides a means of evaluating the efficacy and safety of directacting therapeutics (e.g.…”