Antiretroviral therapy (ART) blocks HIV viral cycle, but does not eliminate latently infected cells. A minority of proviruses integrated among these cells maintain the ability to reactivate, and produce new infectious viral particles. At an estimated frequency of 1 per million CD4+ T cells, identifying the cells responsible for viral rebound is like looking for a needle in a haystack with HIV. One way to assess the potential for reservoir reactivation is HIV-Flow, a flow cytometry technique that allows specific detection of cells expressing the viral capsid (p24) using two .
The reservoir of proviruses found in p24+ cells is inducible and translation-competent, while the one present in p24- cells is rather uninducible and/or incompetent for protein production. Although the proportion of intact proviruses is the same between p24+ and p24-, the proviruses identified by dual viral capsid detection harbor fewer genetic defects. Interestingly, HIV clones are frequently shared between p24+ and p24- memory CD4+ T cells, suggesting that the ability of the provirus to reactivate is influenced by the cellular context. Although there is no phenotypic profile to distinguish p24+ cells with intact proviruses from those with defective HIV genomes, the expression of the integrin VLA-4 (α4β1) is strongly maintained in p24+ where intact and potentially replication-competent HIV genomes are found. Indeed, there is a 27-fold increase in proviruses capable of producing infectious viral particles in memory CD4+ T cells expressing high levels of VLA-4 compared with those expressing no or only low levels.
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