One of the major questions remaining in AIDS research is how the progressionπ of HIV to AIDS might be prevented. Progression rates in infected individuals vary, suggesting that there might be an innate immune mechanism involved in determining how the disease progresses. New research on the simian immunodeficiency virus (SIV), the equivalent of HIV in monkeys, highlights a possible means of protection from AIDS.

SIV infection in natural host species, such as sooty mangabeys, tends to be nonpathogenic. In contrast, SIV infection in rhesus macaques and HIV infection in humans tends to be pathogenic. Recent findings indicate that fundamental differences between the immune responses of sooty mangabeys and of rhesus macaques to SIV may explain the lack of SIV pathogenicity in natural host species (Nat. Med. doi:10.1038/nm.2395; published online 26 June 2011).).

Sooty mangabeys possess fewer immune cells that express CCR5, a co-receptor of the SIV virus that enables its infection of cells, than do rhesus macaques. In this study, Mirko Paiardini of Emory University in Atlanta, GA, and colleagues found that, following immune activation in response to SIV infection, levels of CCR5 in activated immune cells were significantly lower in sooty mangabeys than in rhesus macaques. This difference seemed to be due to a resistance of the sooty mangabey cells to CCR5 upregulation. Additionally, the researchers found lower levels of CCR5 mRNA in sooty mangabey T cells that had been activated in vitro than in activated rhesus macaque T cells.

Further analysis revealed that cells positive for CCR5 proliferate more slowly than cells lacking CCR5, suggesting that CCR5 impedes the ability of cells to proliferate in response to viral infection. Progression to AIDS in SIV-infected rhesus macaques is predicted by depletion of immune cells. The immune cells of the sooty mangabey may be protected from depletion by their lack of CCR5. These results could explain why SIV progresses to AIDS in macaques but not in sooty mangabeys.

The authors propose that in SIV-infected sooty mangabeys, low CCR5 upregulation following immune cell activation protects immune cells from virus-mediated depletion and protects the cells from infection. These results highlight a new and important mechanism of AIDS resistance despite continuous viral infection. This mechanism may prove to be a useful target for treatment approaches that could reduce the pathogenicity of HIV and increase the life expectancy of those living with the disease.