Methamphetamine facilitates HIV infection of primary human monocytes through inhibiting cellular viral restriction factors

Lei, Yu; Meng, Feng-Zhen; Xu, Wenju; Wang, Peng; Liu, Jinbiao; Hu, Wenhui; Young, William A.; Ho, Wen‐Zhe

doi:10.1186/s13578-021-00703-4

Cited by 7 publications

(5 citation statements)

References 68 publications

(62 reference statements)

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“…Gene expression analyses of human macrophages treated with meth could determine the transcriptional pathways that meth alters to mediate differential protein expression. In vivo studies of gene expression in SIV-infected macaque brains exposed to meth found an increased proportion of infected macrophages, which is consistent with our mass spectrometry data and prior in vitro studies [ 92 , 93 ]. These analyses demonstrated the differential expression of genes in the complement pathway and electron transport chain function [ 93 ].…”

Section: Discussionsupporting

confidence: 92%

Methamphetamine Dysregulates Macrophage Functions and Autophagy to Mediate HIV Neuropathogenesis

2022

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HIV-neurocognitive impairment (HIV-NCI) can be a debilitating condition for people with HIV (PWH), despite the success of antiretroviral therapy (ART). Substance use disorder is often a comorbidity with HIV infection. The use of methamphetamine (meth) increases systemic inflammation and CNS damage in PWH. Meth may also increase neuropathogenesis through the functional dysregulation of cells that harbor HIV. Perivascular macrophages are long-lived reservoirs for HIV in the CNS. The impaired clearance of extracellular debris and increased release of reactive oxygen species (ROS) by HIV-infected macrophages cause neurotoxicity. Macroautophagy is a vital intracellular pathway that can regulate, in part, these deleterious processes. We found in HIV-infected primary human macrophages that meth inhibits phagocytosis of aggregated amyloid-β, increases total ROS, and dysregulates autophagic processes. Treatment with widely prescribed ART drugs had minimal effects, although there may be an improvement in phagocytosis when co-administered with meth. Pharmacologically inhibited lysosomal degradation, but not induction of autophagy, further increased ROS in response to meth. Using mass spectrometry, we identified the differentially expressed proteins in meth-treated, HIV-infected macrophages that participate in phagocytosis, mitochondrial function, redox metabolism, and autophagy. Significantly altered proteins may be novel targets for interventional strategies that restore functional homeostasis in HIV-infected macrophages to improve neurocognition in people with HIV-NCI using meth.

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Section: Discussionsupporting

confidence: 92%

Methamphetamine Dysregulates Macrophage Functions and Autophagy to Mediate HIV Neuropathogenesis

2022

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“…Meth increased the amount of HIV released from cells from each independent donor ( Supplementary Figure 2 ). This is consistent with other studies that reported increased HIV infection in other cell types including macrophages ( 46 , 47 ).…”

Section: Resultssupporting

confidence: 93%

Methamphetamine induces transcriptional changes in cultured HIV-infected mature monocytes that may contribute to HIV neuropathogenesis

et al. 2022

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HIV-associated neurocognitive impairment (HIV-NCI) persists in 15-40% of people with HIV (PWH) despite effective antiretroviral therapy. HIV-NCI significantly impacts quality of life, and there is currently no effective treatment for it. The development of HIV-NCI is complex and is mediated, in part, by the entry of HIV-infected mature monocytes into the central nervous system (CNS). Once in the CNS, these cells release inflammatory mediators that lead to neuroinflammation, and subsequent neuronal damage. Infected monocytes may infect other CNS cells as well as differentiate into macrophages, thus contributing to viral reservoirs and chronic neuroinflammation. Substance use disorders in PWH, including the use of methamphetamine (meth), can exacerbate HIV neuropathogenesis. We characterized the effects of meth on the transcriptional profile of HIV-infected mature monocytes using RNA-sequencing. We found that meth mediated an upregulation of gene transcripts related to viral infection, cell adhesion, cytoskeletal arrangement, and extracellular matrix remodeling. We also identified downregulation of several gene transcripts involved in pathogen recognition, antigen presentation, and oxidative phosphorylation pathways. These transcriptomic changes suggest that meth increases the infiltration of mature monocytes that have a migratory phenotype into the CNS, contributing to dysregulated inflammatory responses and viral reservoir establishment and persistence, both of which contribute to neuronal damage. Overall, our results highlight potential molecules that may be targeted for therapy to limit the effects of meth on HIV neuropathogenesis.

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“…Similarly, the use of methamphetamine via IDU or “booty bumping” can result in HIV infection through direct inoculation of the bloodstream from a shared needle or damage the rectal mucosa, which increases biological susceptibility to HIV infection if exposed during condomless receptive anal sex ( Cantrell et al, 2006 ). Methamphetamine also directly alters cellular processes, resulting in decreased intracellular immunity to HIV and greater HIV replication in human monocyte cells ( Liu et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Prevalence and correlates of methamphetamine use in transitional age youth experiencing homelessness or housing instability in San Francisco, CA

Leonard

Broussard

Jain

et al. 2022

J of Nursing Scholarship

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Introduction Substance use, including methamphetamine use, is a contributing factor in HIV acquisition and treatment. Stimulant use is linked to mental health yet there is limited data from youth in community‐based settings. Design One hundred marginally housed or homeless transitional age youth (TAY) were recruited at Larkin Street Youth Services and completed a survey on mental health and substance use. Methods We conducted secondary data analysis using multivariable logistic regression models to identify the correlates of methamphetamine use among TAY. Results The participants’ mean age was 22. Of those who reported methamphetamine use in the past 3 months, 64% were Gay, Bisexual, or Pansexual. Factors independently associated with methamphetamine use were; living with HIV (adjusted odds ratio [aOR] = 3.18, 95% CI = 1.11–9.15), depressive symptoms (aOR = 6.02, 95% CI = 1.46–24.78), symptoms of PTSD (aOR = 13.38, 95% CI = 1.59–112.73), polysubstance use in the past 3 months (aOR = 50.02, 95% CI = 9.72–257.46) and a history of injection drug use (aOR = 8.38, 95% CI = 1.87–37.53). Conclusions Results from this study suggest a need to develop, adapt, and rapidly implement comprehensive interventions that address the combined epidemics of substance use, HIV, and mental health among TAY. Clinical Relevance This article examines factors associated with methamphetamine use among transitional age youth (TAY) experiencing homelessness or housing instability. Several factors were associated with use, including depression, PTSD, HIV status, polysubstance use, and injection drug use. These findings highlight the need for nurses to assess for methamphetamine use among youth as well as associated mental health and physical health problems. Nurses should link TAY who are using methamphetamine to evidence‐based treatment programs to address substance use and comorbid conditions.

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Methamphetamine facilitates HIV infection of primary human monocytes through inhibiting cellular viral restriction factors

Cited by 7 publications

References 68 publications

Methamphetamine Dysregulates Macrophage Functions and Autophagy to Mediate HIV Neuropathogenesis

Methamphetamine Dysregulates Macrophage Functions and Autophagy to Mediate HIV Neuropathogenesis

Methamphetamine induces transcriptional changes in cultured HIV-infected mature monocytes that may contribute to HIV neuropathogenesis

Prevalence and correlates of methamphetamine use in transitional age youth experiencing homelessness or housing instability in San Francisco, CA

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