HIV-associated neurodegenerative disorders: extracellular and intracellular mechanisms.
HIV-associated neurodegenerative disorders: extracellular and intracellular mechanisms.
复制标题
DOI：
10.1097/qad.0000000000002727
复制
发表时间：
2020-12-01
期刊：
影响因子：
--
通讯作者：
Mocchetti I
中科院分区：
文献类型：
--
作者：
Avdoshina V;Mocchetti I
We would like to thank Zhao [1] for expressing the interest in our study [2]. His correspondence [1] is of great interest. Indeed, we and others have shown that the envelope protein gp120 initiates several neurotoxic pathways by either binding to chemokine coreceptors expressed in neurons or other brain cells or by the disruption of the neuronal cytoskeleton. All these proposed mechanisms do not exclude each other and are the result of the experimental conditions used by experimenters (eg concentration, in-vitro and in-vivo models). We also agree that experiments with a pure viral protein do not reproduce a clinical situation seen in people living with HIV; however, animal models, gp120 or other viral proteins are useful tools to study mechanisms of neurotoxicity caused by HIV. Lastly, we also agree with Zhao [1] that more studies, in which one can combine gp120 and other viral proteins, are needed to establish the role of viral proteins in the pathogenesis of HIV-associated neurocognitive disorders (HAND).The importance of studying all molecular mechanisms utilized by HIV to reduce synapses and the survival of brain cells is exemplified by the persistence of HIV in the central nervous system despite the use of the antiretroviral therapy. HIV causes axonal injury [3, 4] and loss of cognitive and motor function [5]. Whether synaptic simplification is caused only by HIV encephalitis (HIVE), a neuroinflammatory condition characterized by the presence of activated microglia, multinucleated giant cells, astrogliosis and myelin loss [6–8], or by a combination of factors, including viral proteins, drug abuse and comorbidities, is a debate not easily solved. Activated microglia is consistent with nonneuronal cells being the primary target cells for HIV; nevertheless, their infection alone does not provide an obvious explanation for the neurological impairment seen in these individuals. Microglia has the ability to release viral proteins; however, this property cannot be tested in humans. Thus, more studies using experimental animals are needed to reveal the mechanisms whereby HIV is neurotoxic and provide new therapeutic targets for an effective prevention of the HIV-mediated neuronal injury.
