Title:Mechanisms of HIV Neuropathogenesis: Role of Cellular Communication Systems
Volume: 14
Issue: 5
Author(s): Shaily Malik and Eliseo A. Eugenin
Affiliation:
Keywords:
HIV, gap junctions, connexin, tunneling nanotubes, exosomes.
Abstract: Background: One of the major complications of Human
Immunodeficiency Virus (HIV) infection is the development of HIV-Associated
Neurocognitive Disorders (HANDs) in approximately 50-60% of HIV infected
individuals. Despite undetectable viral loads in the periphery owing to anti-retroviral
therapy, neuroinflammation and neurocognitive impairment are still prevalent in HIV
infected individuals. Several studies indicate that the central nervous system (CNS)
abnormalities observed in HIV infected individuals are not a direct effect of viral
replication in the CNS, rather these neurological abnormalities are associated with
amplification of HIV specific signals by unknown mechanisms. We propose that
some of these mechanisms of damage amplification are mediated by gap junction
channels, pannexin and connexin hemichannels, tunneling nanotubes and microvesicles/exosomes.
Objective: Our laboratory and others have demonstrated that HIV infection targets cell to cell
communication by altering all these communication systems resulting in enhanced bystander
apoptosis of uninfected cells, inflammation and viral infection. Here we discuss the role of these
communication systems in HIV neuropathogenesis.
Conclusion: In the current manuscript, we have described the mechanisms by which HIV “hijacks”
these host cellular communication systems, leading to exacerbation of HIV neuropathogenesis, and to
simultaneously promote the survival of HIV infected cells, resulting in the establishment of viral
reservoirs.
