Credit: 3D4Medical/Photo Researchers, Inc.

The mechanisms by which HIV-1 infection is controlled—but not eradicated—in less than 1% of infected but untreated individuals are not fully understood. Ivona Pandrea and colleagues now report on a new model of SIV infection of rhesus macaques that may help elucidate the immune mechanisms of viral control in these 'elite controllers' (PLoS Pathog. 7, e1002170).

Using an SIV derived from acute infection of African green monkeys (SIVagm.sab), the researchers infected 12 rhesus macaques and monitored the infection for more than 6 years in some of the animals. Although infection with SIVagm.sab initially paralleled that of both macaque SIV and HIV-1 infections, with substantial replication in both lymphoid and nonlymphoid tissues, high plasma and intestinal viral load, elevated immune activation, and severe CD4+ T cell depletion in the intestinal lamina propria, plasma viral load of SIVagm.sab declined to undetectable by 3 months. CD4+ T cell counts and levels of immune activation also returned to baseline by 4 years after infection in these monkeys. Moreover, all 12 macaques controlled the infection without any significant association with major histocompatibility complex type or host restriction factors.

CD8+ T cell responses are thought to participate in control of HIV-1 infection in human elite controllers, but proof of this is still needed. To address the role of CD8+ T cells in their model, the researchers depleted CD8+ cells in three of the monkeys that had controlled SIVagm.sab infection. Their depletion triggered viral rebound and increased CD4+ T cell activation and loss. Subsequent recovery of CD8+ T cell numbers decreased viral load and increased numbers of CD4+ T cells, indicating that CD8+ cells indeed suppress viral replication in these animals. This model may serve as a useful tool to study the immune mechanisms harnessed by elite controllers to keep HIV-1 infection at bay.