{"id":632058,"date":"2026-09-30T11:52:10","date_gmt":"2026-09-30T11:52:10","guid":{"rendered":"https:\/\/www.newsbeep.com\/il\/632058\/"},"modified":"2026-09-30T11:52:10","modified_gmt":"2026-09-30T11:52:10","slug":"how-an-hiv-protein-disrupts-lipid-metabolism-in-neurons","status":"publish","type":"post","link":"https:\/\/www.newsbeep.com\/il\/632058\/","title":{"rendered":"How an HIV protein disrupts lipid metabolism in neurons"},"content":{"rendered":"

Even when HIV is successfully suppressed, many people continue to experience neurological complications. Although antiretroviral therapy reduces HIV replication to undetectable levels, about 40% of people<\/a> develop HIV-associated neurocognitive disorders. In a study<\/a> from the Journal of Lipid Research, researchers at Temple University found that accumulation of Tat, an HIV protein involved in viral replication, disrupts organelle communication and lipid metabolism in neurons, offering a potential explanation for why these complications persist despite treatment.<\/p>\n

\"\"<\/p>\n

Maryline Santerre<\/p>\n

In neurons, Tat disrupts the tether between the endoplasmic reticulum and the mitochondria, leading to lipid droplet accumulation and metabolic stress.<\/p>\n

Trans-Activator of Transcription, or Tat, is an HIV protein involved in regulating viral replication. Although HIV viral suppression medications reduce HIV viral replication rates, Tat protein still accumulates in neurons. Previous work showed that neuronal Tat disrupts interactions between VAMP\u2013Associated Protein B, or VAPB, on the endoplasmic reticulum and a protein on the mitochondrial outer membrane, weakening the protein tether physically linking these organelles.<\/p>\n

Because communication between the endoplasmic reticulum and mitochondria helps regulate calcium, metabolism and lipid synthesis, the researchers wondered whether Tat might also affect lipid biology. In this study, Maryline Santerre<\/a>, an assistant professor at Temple and first author on the paper, investigated how Tat accumulation altered lipid biology.<\/p>\n

\u201cAt the time, we were working on why people living with HIV have an increased risk of stroke,\u201d said Santerre. \u201cAnd we were like, what about the lipids?\u201d<\/p>\n

Using mass spectrometry and lipidomic analysis, the researchers found large increases in polyunsaturated triglycerides in Tat-treated neurons. Follow-up metabolic analyses revealed reduced levels of several energy-related molecules, suggesting that neurons were accumulating lipids but not efficiently using them for energy.<\/p>\n

To assess whether Tat accumulation alters metabolism, Santerre conducted a metabolic panel to probe for various metabolic intermediates. She found that neurons treated with Tat had a significant decrease in the energy-carrying molecules adenosine triphosphate, or ATP, and nicotinamide adenine dinucleotide, or NAD, indicating cellular energy deficits. Acetyl-CoA, a molecule produced during fatty acid breakdown, also decreased, hinting that polyunsaturated triglycerides are not metabolized.<\/p>\n

In addition to helping connect the endoplasmic reticulum and mitochondria, VAPB helps move lipids between cellular compartments. Tat-treated neurons showed disrupted Golgi organization and accumulated more and larger lipid droplets, hinting that lipids are no longer being efficiently transported or used. Loss of VAPB alone produced similar effects, identifying the protein as a driver of the observed metabolic and lipid dysfunction.<\/p>\n

Overall, Santerre discovered that Tat accumulation disrupts VAPB-dependent organelle communication, leading to metabolic stress and impaired lipid trafficking. As a result, lipids that would normally be used to build cellular membranes or generate energy are instead diverted into lipid droplets.<\/p>\n

To explain the phenomenon, Santerre compares it to a supply-chain bottleneck with a blocked distribution network.<\/p>\n

\u201cOne analogy is a supply chain bottleneck: the raw materials are still present,\u201d Santerre said. \u201cBut if the transfer points are blocked, materials pile up in storage instead of reaching the places where they are needed.\u201d<\/p>\n

Next, Santerre plans to test these findings in models that better reflect human disease and identify exactly where lipid transport breaks down.<\/p>\n

Her goal is to understand why neurological complications persist even when HIV is successfully treated.<\/p>\n

\u201c(This work) is about understanding why treated HIV can still leave people with neurological risk, and how we might eventually protect the brain more effectively,\u201d she said.<\/p>\n","protected":false},"excerpt":{"rendered":"Even when HIV is successfully suppressed, many people continue to experience neurological complications. Although antiretroviral therapy reduces HIV…\n","protected":false},"author":2,"featured_media":632059,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[163,85,46],"class_list":["post-632058","post","type-post","status-publish","format-standard","has-post-thumbnail","category-health","tag-health","tag-il","tag-israel"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/posts\/632058","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/comments?post=632058"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/posts\/632058\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/media\/632059"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/media?parent=632058"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/categories?post=632058"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/tags?post=632058"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}