Neuronal Toxicity in HIV CNS Disease

Abstract

HIV enters the brain during the early stages of initial infection and can result in a complicated array of diverse neurological dysfunctions. While neuronal injury and loss are at the heart of neurological decline and HIV-associated neuropathology, HIV does not productively infect neurons and the effects of HIV on neurons may be described as largely indirect. Viral proteins released from infected cells in the CNS are a well-characterized source of neuronal toxicity. Likewise, host-derived inflammatory cytokines and chemokines released from infected and/or activated glial cells can damage neurons, as well. Newly identified host–virus interactions and the current state of our knowledge regarding HIV-associated neuronal toxicity will be addressed in this review. Aspects of HIV-associated neurotoxic mechanisms, patterns of neuronal damage, viral effects on neurotrophic signaling, clade variations and comorbid substance abuse will be discussed. Recent advances in our understanding of the impact of HIV infection of the CNS on neuronal dysfunction and cell death will also be highlighted.

Characterization of neuropathology in the HIV-1 transgenic rat at different ages

“…The exact neuropathology leading to milder forms of HIV-associated neurocognitive disorders (HAND) is not fully understood but is probably multifactorial. Unlike microglia and astrocytes, neurons do not seem to get productively infected with HIV (Kovalevich and Langford, 2012). The neurologic damage is rather thought related to persistent low level neuroinflammation (Desplats et al, 2013), neurotoxic effects of viral proteins (Agrawal et al, 2012, Hu et al, 2009, Mocchetti et al, 2011), as well as the disruption of the supportive and neurotrophic role of astrocytes (Bezzi et al, 2001) and oligodendrocytes (Radja et al, 2003).…”

Rabies Virus Envelope Glycoprotein Targets Lentiviral Vectors to the Axonal Retrograde Pathway in Motor Neurons

“…Previous experiments have studied the trafficking of labeled HIV-1 and demonstrated that HIV-1 capsids are also able to undergo dynein-mediated trafficking to the nucleus (17,18); however, because native HIV-1 is unable to infect neurons (for a review, see Ref. 19), it is currently unclear whether these capsids can reach the nucleus from such distal sites as the neuromuscular junction.…”

Trastornos neuropsiquiátricos en la población con VIH: una revisión narrativa

“…Debido a que pierden gran parte de sus funciones, los linfocitos no generan una respuesta inmune adecuada y no generan las citocinas que estimulan otras células, como los linfocitos B, para montar una respuesta inmunitaria ante microrganismos y células tumorales, junto con una menor supervivencia de estos linfocitos no funcionales, debido a la mala ejecución y acortamiento de sus telomerasas. Todo este proceso de inmunosenescencia ocurre de la mano con el incremento de marcadores inflamatorios, y ambos procesos en conjunto se conocen con el término inflamm-aging [28].…”