HIV-1-Infected Astrocytes and the Microglial Proteome

Abstract

The human immunodeficiency virus (HIV) invades the central nervous system early after viral exposure but causes progressive cognitive, behavior, and motor impairments years later with the onset of immune deficiency. Although in the brain, HIV preferentially replicates productively in cells of mononuclear phagocyte (MP; blood borne macrophage and microglia), astrocytes also can be infected, at low and variable frequency, particularly in patients with encephalitis. Among their many functions, astrocytes network with microglia to provide the first line of defense against microbial infection; however, very little is known about its consequences on MP. Here, we addressed this question using co-culture systems of HIV infected mouse astrocytes and microglia. Pseudotyped vesicular stomatis virus/HIV was used to circumvent absence of viral receptors and ensure cell genotypic uniformity for studies of intercellular communication. The study demonstrated that infected astrocytes show modest changes in protein elements as compared to uninfected cells. In contrast, infected astrocytes induce robust changes in the proteome of HIV-1 infected microglia. Accelerated cell death and redox proteins, amongst others, were produced in abundance. The observations confirmed the potential of astrocytes to influence the neuropathogenesis of HIV-1 infection by specifically altering the neurotoxic potential of infected microglia and in this manner, disease progression.

Tobacco smoking effect on HIV-1 pathogenesis: role of cytochrome P450 isozymes

“…Astrocytes, the most abundant glial cells in the brain, which are important to protect the integrity as well as nourishment of neurons, play a major role in the pathology of HAND [72]. Astrocytes are also known to be infected by HIV-1, though to a lesser extent compared to microglia [73]. In addition, viral proteins and cytokines released by HIV-1-infected microglia are known to damage astrocytes [72], which may ultimately lead to HAND.…”

Role of p53 in Neurodegenerative Diseases

“…Neurodegenerative Dis 2012;9:68-80 71 prevalent [55] . In addition, several of the minor cognitive motor disorder cases have latent infection -given the success of the therapy, it is probable such cases remain because there are more latent cases [55][56][57] .…”

“…The restricted infection of astrocytes has also been reported. This type of infection may result in viral latency and the release of a small number of viruses upon simulation by cytokines [71] . Even though traces of HIV-1 DNA and RNA have been detected in neurons, there is little evidence of productive infection in neurons [72][73][74] .…”

Combined analysis of the glia secretome and the CSF proteome: neuroinflammation and novel biomarkers

“…Microglia and astrocytes secrete numerous proteins that play an important role in the CNS physiology and pathology. Microglia and astrocytes are also known to interact with each other through the secreted mediators [56][57][58][59][60]. Protein secretion profiles of microglia and astrocytes can be mutually regulated.…”

“…The exosomal CD13 plays an important role in CNS cellular communication by cleaving neuropeptides. The proteome of a HIV-infected coculture of microglia and astrocytes was analyzed to demonstrate that infected astrocytes induce robust changes in the proteome of microglia; for instance, accelerated cell death and redox proteins were produced in abundance [59]. Interactions within the glial cell population were also studied by proteomic ana lysis of astrocytes cultured with microglia-conditioned media [60].…”