HIV infection of susceptible cells, such as CD4+ T-cells, is mediated by the interaction of CD4 and a cell surface chemokine co-receptor with the gp120 envelope protein. The HIV viral particle initially binds via its gp120 envelope protein to the CD4 receptor of the target cell. A conformational change occurs in gp120 that results in its subsequent binding to a chemokine receptor, such as CCR5. See, e.g., Wyatt et al., Science, 280:1884-1888 (1998). HIV-1 isolates arising subsequently in the infection bind to the CXCR4 chemokine receptor.
HIV does not immediately replicate in all infected cells, but instead can progress to a state of latent infection, where the HIV is dormant. Upon activation of a latent infected cell, for example by engaging T-cell surface CD3 and CD28, the “dormant” HIV virus can become activated, initiating the process of viral replication. HIV replication results in the production of infectious HIV particles, facilitating the spread of the infection throughout the subject cells.
The pool of latently infected cells in the resting CD4+ T-cell compartment is considered one of the major impediments to HIV eradication. When latently infected, resting T-cells become reactivated, viral particles released during the reactivation process can spread to and infect resting T-cells, as well as activated CD4+ T-cells. This reactivation process can facilitate the continual replenishment of the CD4+ T-cell reservoir, offsetting the benefits of antiviral therapy, such as HAART, and contributing to the persistence of HIV and initiation of new infection cycles. See, e.g., Chun et al., J. Clin. Invest. 115:3250-3255, 2005.
Accordingly, methods capable of detecting and treating HIV infection during its latent phase are needed.