Figure 2. The efficiency of establishing and reversing latent infection is dependent on the mechanism of resting CD4+ T cell infection.

Various modes of HIV-1 infection of resting CD4+ T cells are depicted with their corresponding efficiency for establishing infection and reversible latent infection. Although no study has compared all of these mechanisms side-by-side, we estimated infection and latency reversal efficiency qualitatively based on published observations. Light blue arrows represent lower relative levels of HIV-1 infection or latency reversion and dark blue arrows correspond to higher relative levels. A. Cell-free infection results in lower relative levels of infection (light blue arrow) but the establishment of a moderately inducible latent population (medium blue)(Agosto et al., 2018; Lassen et al., 2012; Swiggard et al., 2005). B. Cell-free infections aided by chemokines, such as CCL19 and CCL21, result in increased resting cell susceptibility to infection compared to infections without added chemokines and a moderately inducible latent population (Cameron et al., 2010; Kumar et al., 2018; Saleh et al., 2007). C. An uninfected HIV-1-carrying cell contacts an uninfected CD4+ T cell. Virus is transmitted in trans via the infectious synapse. This mode of transmission promotes latent infection of resting CD4+ T cells. However, the reversion of latent infection varies widely depending on the HIV-1-transmitting cell type, indicated by the light, medium and dark blue arrows (Kumar et al., 2015). The efficiency of latency reversion also depends whether or not the target cells are proliferating during infection in APC co-cultures (Kumar et al., 2018). D. An infected donor cell establishes contact with an uninfected donor cell and transmits HIV-1 via a virological synapse. This is an efficient method of transmission and results in moderate levels of resting cell infection. However, although latent infection can be detected in target cells by HIV-1 DNA, viral re-expression is not readily induced (Agosto et al., 2018). E. The susceptibility of resting CD4+ T cells to HIV-1 infection increases when in contact with endothelial cells and enables the establishment inducible latent infection (Choi et al., 2005a; Choi et al., 2005b; Schilthuis et al., 2018; Shen et al., 2013).