From Elite Controllers to Stoned Monkeys

Speakers today continued to discuss the development of nonhuman primate (NHP) models that can mimic different aspects of HIV infection and pathogenesis. Cristian Apetrei from the University of Pittsburgh described the development of an NHP model of elite controllers, HIV-infected individuals who control virus replication below detectable levels without treatment. Apetrei and colleagues infected rhesus macaques with simian immunodeficiency virus (SIV)agm, the SIV that naturally infects African green monkeys without causing disease. The rhesus macaques infected this way showed symptoms resembling human elite controllers. Apetrei said that having such a model is important because it makes it possible to study how elite control develops early after infection. 

Other speakers discussed the pathogenic effects of SIV infection in NHPs. One important example is chronic immune activation, which is a hallmark of HIV infection. Structural damage to the gut is thought to contribute to this immune activation because of bacterial translocation from the gut into the blood. The mechanism of this is still largely unclear, but Nichole Klatt from the National Institute of Allergy and Infectious Diseases reported the identification of a new type of natural killer cells in the gut that can produce Interleukin (IL)-17. Klatt showed evidence that SIV infection of rhesus macaques results in the loss of these cells in the gut and that this loss is associated with damage to the colon epithelium and with immune activation. 

One part of the body that is discussed less often when it comes to HIV infection and pathogenesis is the brain. Xavier Alvarez from the Tulane National Primate Research Center reported evidence today that the brain could be an important reservoir for the virus. He infected monkeys with SIV and labeled cells in the brain with nanoparticles to show that macrophages, some of them SIV infected, actually migrate out of the brain. This is the first time, he said, that cells have been shown to migrate out of the brain and suggests that the brain could be an important reservoir for the virus. 

The brain is also the target of drugs like marijuana, and in today’s last talk, Edith Walker from Louisiana State University discussed an aspect of marijuana that hasn’t been looked at very carefully: its effect on HIV or SIV infection. Studying this is important, Walker said, because people use marijuana recreationally and because HIV-infected people use delta-9-tetrahydrocannabinol (THC), the primary psychoactive component of marijuana, as a therapeutic to ameliorate the wasting that is associated with end-stage disease. “In a recent survey of HIV-infected patients in Canada, 43% reported regular marijuana use as recreational or therapeutic,” Walker said. 

Walker reported today that THC does indeed have a long-term effect. When rhesus macaques were given THC twice daily for 15-18 months and then infected with SIV, there was a trend toward reduced viral load in the plasma, and there was less viral RNA and DNA in the spleen. This, she said, suggests that chronic THC administration may ameliorate disease progression. 

Asked if the monkeys get stoned, Walker said that the THC dose was chosen so that it eliminated the monkey’s ability to respond to a complex behavioral task such as learning a series of lights and then pushing the right sequence to get a reward. “Actually they don’t even bother trying [to push the right light sequence] at some point,” Walker said.