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

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Chilunda, VanessaAlbert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA. (author)

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

Article/chapterEnglish2022

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2022-08-18
Frontiers Media S.A.2022
electronicrdacarrier

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LIBRIS-ID:oai:DiVA.org:uu-484902
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-484902URI
https://doi.org/10.3389/fimmu.2022.952183DOI

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Language:English
Summary in:English

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

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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.

Subject headings and genre

NATURVETENSKAP Biologi Immunologi hsv//swe
NATURAL SCIENCES Biological Sciences Immunology hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Infektionsmedicin hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Infectious Medicine hsv//eng
methamphetamine
monocytes
HIV
neuroinflammation
migration
viral reservoirs

Added entries (persons, corporate bodies, meetings, titles ...)

Weiselberg, JessicaAlbert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA. (author)
Martinez-Meza, SamuelAlbert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA. (author)
Mhamilawa, Lwidiko EUppsala universitet,Internationell barnhälsa och nutrition,Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA.;Muhimbili Univ Hlth & Allied Sci, Dept Parasitol & Med Entomol, Dar Es Salaam, Tanzania.(Swepub:uu)lwied894 (author)
Cheney, LauraAlbert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA.;Montefiore Med Ctr, Dept Med, Div Infect Dis, Bronx, NY USA.;Albert Einstein Coll Med, Bronx, NY 10467 USA. (author)
Berman, Joan W.Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA.;Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. (author)
Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA.Internationell barnhälsa och nutrition (creator_code:org_t)

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