Making sense of how HIV kills infected CD4 T cells: implications for HIV cure

Abstract

Defining how HIV does, and does not, kill the host CD4 T cell that it infects is of paramount importance in an era when research is approaching a cure for infection. Three mutually exclusive pathways can lead to the death of HIV-infected cells during the HIV life cycle, before, coincident and after HIV integration and consequently may affect viral replication. We discuss the molecular mechanism underlying these pathways, the evidence supporting their roles in vivo, and contemplate how understanding these pathways might inform novel approaches to promote viral cure of HIV.

Keywords: Apoptosis; Casp8p41; Caspase 1; Cure; DNA-PK; HIV; IFI16; Inflammation; Pyroptosis.

Figure 1

Pathways of CD4 T cell death in HIV infection. Depicted are the described pathways for both uninfected and infected CD4 T cell death in the context of HIV infection and whether progeny virions are produced as a result of the pathway. Examples are provided describing the pathogenicity of the pathway in relevant in vitro models. Specific in vivo support of the pathwaysm biologic relevance are also described. Theoretical ways to inhibit the described pathways are conjectured. References [–, –44].