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Leukotrienes inhibit early stages of HIV-1 infection in monocyte-derived microglia-like cells

DOI: 10.1186/1742-2094-9-55

Keywords: Central nervous system, Microglia, HIV-1, Leukotrienes

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Abstract:

To evaluate the role of LTs on HIV-1 infection in the CNS, monocyte-derived microglial-like cells (MDMis) were utilized in this study. Leukotriene-treated MDMis were infected with either fully replicative brain-derived HIV-1 isolates (YU2) or R5-tropic luciferase-encoding particles in order to assess viral production and expression. The efficacy of various steps of the replication cycle was evaluated by means of p24 quantification by ELISA, luciferase activity determination and quantitative real-time polymerase chain reaction (RT-PCR).We report in this study that virus replication is reduced upon treatment of MDMis with LTB4 and LTC4. Additional experiments indicate that these proinflammatory molecules alter the pH-independent entry and early post-fusion events of the viral life cycle. Indeed, LT treatment induced a diminution in integrated proviral DNA while reverse-transcribed viral products remained unaffected. Furthermore, decreased C-C chemokine receptor type 5 (CCR5) surface expression was observed in LT-treated MDMis. Finally, the effect of LTs on HIV-1 infection in MDMis appears to be mediated partly via a signal transduction pathway involving protein kinase C.These data show for the first time that LTs influence microglial cell infection by HIV-1, and may be a factor in the control of viral load in the CNS.Infection of the central nervous system (CNS) by human immunodeficiency virus type 1 (HIV-1) causes neurotoxicity and inflammatory disorders such as encephalitis and associated neurocognitive deficits [1]. Since the introduction of highly active antiretroviral therapy (HAART) as the standard of care for seropositive patients, the incidence of severe neurological complications caused by HIV-1 such as dementia has greatly diminished, but a more subtle form of CNS dysfunction known as minor cognitive and motor disorder has emerged [2]. Although a discordance between cerebrospinal fluid (CSF) and plasma viral load is often observed, sustained virus replicatio

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