In Vitro and In Vivo Models of HIV Latency

Adv Exp Med Biol. 2018:1075:241-263. doi: 10.1007/978-981-13-0484-2_10.

Abstract

Latently infected cells are very infrequent in CD4+ T cells from antiretroviral (ARV) treated individuals, with only approximately one in a million infected CD4+ T cells in blood. Given the low frequency of infected cells in vivo, multiple in vitro latency models have been developed to facilitate investigations into mechanisms of HIV latency, as well as to enable the evaluation of pharmacological and immunological interventions aimed at depleting latently infected cells. These in vitro models include clones of transformed cell lines with integrated HIV proviruses or primary CD4+ T cells from uninfected donors that have been infected with HIV in particular conditions. This chapter presents a description of these various in vitro models, along with an overview of their advantages and limitations.Preclinical animal models represent a critical bridge between in vitro studies and human clinical trials. Simian immunodeficiency virus (SIV) infection of Indian origin rhesus macaques has been well established as an informative model of HIV infection. Recent years have seen breakthroughs in ARVs that permit the potent suppression of SIV replication, enabling studies of latency and putative curative interventions in this model. Small animal models of HIV infection can be generated by engrafting immunodeficient mice with human immune cells. These "humanized mice" have provided valuable insights into HIV pathogenesis and are under development as models for studying HIV latency. We summarize both the promise of these models and outstanding challenges that remain to be overcome to realize their potential to inform efforts to cure HIV infection.

Keywords: Cell line latency model; HIV latency; Humanized mice; Nonhuman primate latency model; Primary cell latency model.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-HIV Agents / pharmacology
  • Anti-HIV Agents / therapeutic use
  • CD4-Positive T-Lymphocytes / virology
  • Cell Line, Transformed
  • Cells, Cultured
  • Clone Cells / virology
  • Coculture Techniques
  • Graft vs Host Disease
  • HIV-1 / drug effects
  • HIV-1 / physiology*
  • Heterografts
  • Humans
  • In Vitro Techniques
  • Macaca mulatta
  • Mice
  • Mice, Nude
  • Radiation Chimera
  • Simian Acquired Immunodeficiency Syndrome / virology
  • Simian Immunodeficiency Virus / physiology
  • Virus Latency* / drug effects
  • Virus Replication / drug effects

Substances

  • Anti-HIV Agents