Researchers at UCLA and Purdue University recently demonstrated that certain HIV protease inhibitors – crucial drugs for HIV treatment – block a cellular enzyme that is important to the structure of the cell nucleus. This link may explain some side effects for HIV treatment, such as metabolic syndrome and losing body fat in specific regions. “We show, for the first time, that certain HIV protease inhibitor drugs directly inhibit an enzyme called ZMPSTE24, which is important for generating the structural scaffolding supporting the cell nucleus,” said Catherine Coffinier, author of the study and an assistant researcher at the David Geffen School of Medicine at UCLA. The research team added HIV protease inhibitors to cultures of human and mouse fibroblast cells and found that the inhibition of ZMPSTE24 by the HIV protease inhibitor drugs led to an accumulation of prelamin A – a key molecule in the structural scaffolding for the cell nucleus. Progeria, an accelerated aging syndrome, can be caused by genetic defects that interfere with the conversion of prelamin A to lamin A. “Since HIV protease inhibitors interfere with the conversion of prelamin A to lamin A, we believe — at least at a biochemical level — that there is a link between progeria syndromes and HIV treatment regimens,” said Loren Fong, associate professor of medicine at the David Geffen School of Medicine.
Researchers at the San Diego HIV Neurobehavioral Research Center found that hepatitis C virus (HCV) can travel into the brain and replicate there causing cognitive impairment in people infected with both HIV and HCV. Researchers studied the brain tissue of 25 patients after their death and found HCV RNA in the brain tissue of all the HIV/HVC co-infected subjects, but none of the HCV negative individuals. The researchers also looked at the cognitive abilities of the subjects, assessed before death, and found that the presence of HCV RNA was significantly associated with considerable cognitive impairment as well as the presence of brain tissue inflammation, or encephalitis. The findings of this study suggest that HCV and HIV might be working together to block clearance of glutamate from the synapses of people with the co-infection, possibly leading to structural damage in the brain and therefore cognitive impairment.
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