{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T02:53:04Z","timestamp":1789786384233,"version":"4.0.1"},"reference-count":78,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,4]],"date-time":"2026-01-04T00:00:00Z","timestamp":1767484800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01 NS082116"],"award-info":[{"award-number":["R01 NS082116"]}]},{"name":"NIH","award":["U54GM115458"],"award-info":[{"award-number":["U54GM115458"]}]},{"name":"NIH","award":["T32 MH079785"],"award-info":[{"award-number":["T32 MH079785"]}]},{"name":"Comprehensive NeuroHIV Center","award":["P30 MH092177"],"award-info":[{"award-number":["P30 MH092177"]}]},{"name":"NIH Nonhuman Primate Reagent Resource","award":["P40 OD028116"],"award-info":[{"award-number":["P40 OD028116"]}]},{"name":"NIH Nonhuman Primate Reagent Resource","award":["U24 AI126683"],"award-info":[{"award-number":["U24 AI126683"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>HIV-associated distal sensory polyneuropathy (HIV-DSP) remains prevalent even in the antiretroviral therapy (ART) era. Previously, we identified the upregulation of nociceptive ion channels transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1) in the dorsal root ganglia (DRG) of simian immunodeficiency virus (SIV)-infected ART-treated macaques. To investigate upstream mechanisms, we performed bulk RNA-seq and pathway analysis on DRGs from uninfected, SIV-infected, and SIV-infected\/ART macaques. SIV infection drove strong activation of upstream regulators of interferon \u03b3 (IFN\u03b3) and lipopolysaccharide (LPS). Although ART reduced overall IFN\u03b3 and LPS pathway activity, the IFN\u03b3-inducible chemokines C-X-C motif chemokine ligand (CXCL)9 and CXCL10 remained significantly upregulated. To determine whether these chemokines influence TRPV1\/TRPA1 expression, we treated induced pluripotent stem cell-derived peripheral sensory neurons (iPSC-PSNs) with CXCL9 and CXCL10, which induced a significant increase in TRPV1 but not TRPA1 expression. In parallel experiments, IFN\u03b3 but not LPS stimulated monocyte-derived macrophages (MDMs) to release CXCL9 and CXCL10. Conditioned media from IFN\u03b3-treated MDMs modestly increased TRPV1 expression in iPSC-PSNs, and pharmacological inhibition of CXCR3, the receptor of CXCL9\/10, did not reduce this effect. Together, these data indicate that persistent IFN\u03b3-driven CXCL9\/10 signaling may be one contributor to nociceptor sensitization underlying HIV-DSP, even in the presence of ART.<\/jats:p>","DOI":"10.3390\/ijms27010523","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T13:35:47Z","timestamp":1767620147000},"page":"523","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["CXCL9 and CXCL10 Induce Expression of Nociceptive Ion Channels in Primary Sensory Neurons in Models of HIV-Associated Distal Sensory Polyneuropathy"],"prefix":"10.3390","volume":"27","author":[{"given":"Rebecca","family":"Warfield","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology, and Inflammation, Center for NeuroVirology and Gene Editing, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jake A.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2285-7676","authenticated-orcid":false,"given":"Stephen","family":"Baak","sequence":"additional","affiliation":[{"name":"Department of Medicine, Rutgers Institute of Translational Medicine and Science, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, 89 French Street, New Brunswick, NJ 08901, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1467-0921","authenticated-orcid":false,"given":"Rachel M.","family":"Podgorski","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Inflammation, Center for NeuroVirology and Gene Editing, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara A.","family":"Gabor","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Inflammation, Center for NeuroVirology and Gene Editing, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Caocci","sequence":"additional","affiliation":[{"name":"Department of Medicine, Rutgers Institute of Translational Medicine and Science, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, 89 French Street, New Brunswick, NJ 08901, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1055-3728","authenticated-orcid":false,"given":"Meng","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6350-5581","authenticated-orcid":false,"given":"Andrew D.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Population Medicine and Diagnostic Sciences, Section of Anatomic Pathology, Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2032-374X","authenticated-orcid":false,"given":"Howard S.","family":"Fox","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4224-7381","authenticated-orcid":false,"given":"Tricia H.","family":"Burdo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Rutgers Institute of Translational Medicine and Science, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, 89 French Street, New Brunswick, NJ 08901, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1097\/j.pain.0000000000001365","article-title":"The IASP classification of chronic pain for ICD-11: Chronic neuropathic pain","volume":"160","author":"Scholz","year":"2019","journal-title":"Pain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"939","DOI":"10.4103\/1673-5374.250566","article-title":"Gene expression changes in dorsal root ganglia following peripheral nerve injury: Roles in inflammation, cell death and nociception","volume":"14","author":"Martin","year":"2019","journal-title":"Neural Regen. 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