title: Breaking down the barrier: the effects of HIV-1 on the blood-brain barrier.
abstract: Human immunodeficiency virus type 1 (HIV-1) primarily infects CD4(+) T cells and cells of the monocyte-macrophage lineage, resulting in immunodeficiency in an infected patient. Along with this immune deficiency, HIV-1 has been linked to a number of neurological symptoms in the absence of opportunistic infections or other co-morbidities, suggesting that HIV-1 is able to cross the blood-brain barrier (BBB), enter the central nervous system (CNS), and cause neurocognitive impairment. HIV-1-infected monocyte-macrophages traverse the BBB and enter the CNS throughout the course of HIV-1 disease. Once in the brain, both free virus and virus-infected cells are able to infect neighboring resident microglia and astrocytes and possibly other cell types. HIV-1-infected cells in both the periphery and the CNS give rise to elevated levels of viral proteins, including gp120, Tat, and Nef, and of host inflammatory mediators such as cytokines and chemokines. It has been shown that the viral proteins may act alone or in concert with host cytokines and chemokines, affecting the integrity of the BBB. The pathological end point of these interactions may facilitate a positive feedback loop resulting in increased penetration of HIV into the CNS. It is proposed in this review that the dysregulation of the BBB during and after neuroinvasion is a critical component of the neuropathogenic process and that dysregulation of this protective barrier is caused by a combination of viral and host factors including secreted viral proteins, components of the inflammatory process, the aging process, therapeutics, and drug or alcohol abuse.
authors.affiliation: Department of Microbiology and Immunology, and Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
authors.forename: Marianne
authors.initials: M
authors.lastname: Strazza
authors.forename: Vanessa
authors.initials: V
authors.lastname: Pirrone
authors.forename: Brian
authors.initials: B
authors.lastname: Wigdahl
authors.forename: Michael R
authors.initials: MR
authors.lastname: Nonnemacher
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000276:immunology / Q000503:physiopathology*; D006678:HIV / Q000472:pathogenicity*; D015658:HIV Infections / Q000276:immunology / Q000473:pathology*; D006801:Humans; D008264:Macrophages / Q000276:immunology; D008954:Models, Biological