---
title: "Secreted ORF8 Reprograms Macrophages to Enhance SARS-CoV-2 Infection of Lung Epithelial Cells"
id: "pubmed-42758812"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42758812"
content_type: "clinical_feed_article"
specialty: "Critical Care"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42758812/"
doi: "10.1126/sciadv.aee5421"
published_at: "2026-09-18T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Secreted ORF8 Reprograms Macrophages to Enhance SARS-CoV-2 Infection of Lung Epithelial Cells
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42758812
- **Specialty:** [Critical Care](https://medichelpline.com/clinical-feed/critical-care.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42758812/)
- **DOI:** [10.1126/sciadv.aee5421](https://doi.org/10.1126%2Fsciadv.aee5421)
- **Published At:** 2026-09-18T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- The article titled “Secreted ORF8 reprograms macrophages to enhance SARS-CoV-2 infection of lung epithelial cells” was published in Sci Adv on 18 September 2026 (Vol. 12, Issue 38) with DOI 10.1126/sciadv.aee5421 and PMID 42758812. - The paper’s central claim, as stated in the title, is that a secreted viral protein, **ORF8**, alters macrophage behavior in a way that increases infection of lung epithelial cells by **SARS-CoV-2**. - Authors include Yusuke Matsui, Rahul K. Suryawanshi, Mauricio Montano, and multiple collaborators from institutions such as the J. David Gladstone Institutes, UCSF, NIAID Rocky Mountain Laboratories, and Biohub. - Affiliations listed indicate multidisciplinary input from virology, immunology, bioengineering, cardiovascular research, and clinical departments. - The title implies a cell–cell interaction axis: a viral secreted factor acting on innate immune cells (**macrophages**) with downstream effects on **lung epithelial cell** susceptibility. - Specific experimental methods, quantitative results, mechanistic details, model systems (in vitro, ex vivo, or in vivo), and statistical outcomes are not reported in the PubMed page content provided. - The PubMed entry includes standard bibliographic metadata (journal, date, DOI, PMID, author list, and affiliations) but the abstract and detailed findings were not included in the supplied source text. - Because the underlying methods and data are not present in the provided source, no additional claims about mechanism, effect size, or therapeutic implications can be stated beyond what the title and bibliographic record convey. - Clinically, the title highlights a potential viral immune-modulatory protein (**ORF8**) that may influence lung infection dynamics, a topic relevant to understanding pathogenesis and potential intervention points for COVID-19; however, evidence details are not available in the supplied source.
## Clinical Analysis & Structured Key Points
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Epub 2026 Sep 18. # Secreted ORF8 reprograms macrophages to enhance SARS-CoV-2 infection of lung epithelial cells [Yusuke Matsui](https://pubmed.ncbi.nlm.nih.gov/?term=Matsui+Y&cauthor_id=42758812)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#full-view-affiliation-1 "J. David Gladstone Institutes; San Francisco, CA, USA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#full-view-affiliation-2 "Michael Hulton Center for HIV Cure Research at Gladstone; San Francisco, CA, USA."), [Rahul K Suryawanshi](https://pubmed.ncbi.nlm.nih.gov/?term=Suryawanshi+RK&cauthor_id=42758812)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#full-view-affiliation-3 "Laboratory of Neurological Infections and Immunity, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Rocky Mountain Laboratories; Hamilton, MT, USA."), [Mauricio Montano](https://pubmed.ncbi.nlm.nih.gov/?term=Montano+M&cauthor_id=42758812)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#full-view-affiliation-1 "J. David Gladstone Institutes; San Francisco, CA, USA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#full-view-affiliation-2 "Michael Hulton Center for HIV Cure Research at Gladstone; San Francisco, CA, USA."), [Taha Y Taha](https://pubmed.ncbi.nlm.nih.gov/?term=Taha+TY&cauthor_id=42758812)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#full-view-affiliation-1 "J. David Gladstone Institutes; San Francisco, CA, USA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#full-view-affiliation-2 "Michael Hulton Center for HIV Cure Research at Gladstone; San Francisco, CA, USA.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#full-view-affiliation-4 "Department of Bioengineering and Therapeutic Sciences, University of California San Francisco; San Francisco, CA, USA."), [Mir M Khalid](https://pubmed.ncbi.nlm.nih.gov/?term=Khalid+MM&cauthor_id=42758812)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#full-view-affiliation-1 "J. David Gladstone Institutes; San Francisco, CA, USA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#full-view-affiliation-2 "Michael Hulton Center for HIV Cure Research at Gladstone; San Francisco, CA, USA."), [Limeng Sun](https://pubmed.ncbi.nlm.nih.gov/?term=Sun+L&cauthor_id=42758812)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#full-view-affiliation-1 "J. David Gladstone Institutes; San Francisco, CA, USA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#full-view-affiliation-2 "Michael Hulton Center for HIV Cure Research at Gladstone; San Francisco, CA, USA."), [Kanika Khanna](https://pubmed.ncbi.nlm.nih.gov/?term=Khanna+K&cauthor_id=42758812)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#full-view-affiliation-1 "J. David Gladstone Institutes; San Francisco, CA, USA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#full-view-affiliation-2 "Michael Hulton Center for HIV Cure Research at Gladstone; San Francisco, CA, USA."), [Jin Tang](https://pubmed.ncbi.nlm.nih.gov/?term=Tang+J&cauthor_id=42758812)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#full-view-affiliation-1 "J. David Gladstone Institutes; San Francisco, CA, USA.")[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#full-view-affiliation-5 "Quantitative Biosciences Institute \(QBI\), University of California San Francisco; San Francisco, CA, USA."), [Yuan Zhou](https://pubmed.ncbi.nlm.nih.gov/?term=Zhou+Y&cauthor_id=42758812)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#full-view-affiliation-1 "J. David Gladstone Institutes; San Francisco, CA, USA.")[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#full-view-affiliation-5 "Quantitative Biosciences Institute \(QBI\), University of California San Francisco; San Francisco, CA, USA."), [Robyn M Kaake](https://pubmed.ncbi.nlm.nih.gov/?term=Kaake+RM&cauthor_id=42758812)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#full-view-affiliation-1 "J. David Gladstone Institutes; San Francisco, CA, USA.")[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#full-view-affiliation-5 "Quantitative Biosciences Institute \(QBI\), University of California San Francisco; San Francisco, CA, USA."), [Xiaohui Fang](https://pubmed.ncbi.nlm.nih.gov/?term=Fang+X&cauthor_id=42758812)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#full-view-affiliation-6 "Cardiovascular Research Institute, University of California San Francisco; San Francisco, CA, USA."), [Mazharul Maishan](https://pubmed.ncbi.nlm.nih.gov/?term=Maishan+M&cauthor_id=42758812)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#full-view-affiliation-6 "Cardiovascular Research Institute, University of California San Francisco; San Francisco, CA, USA."), [Michael A Matthay](https://pubmed.ncbi.nlm.nih.gov/?term=Matthay+MA&cauthor_id=42758812)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#full-view-affiliation-6 "Cardiovascular Research Institute, University of California San Francisco; San Francisco, CA, USA.")[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#full-view-affiliation-7 "Department of Anesthesia, University of California San Francisco; San Francisco, CA, USA.")[ 8 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#full-view-affiliation-8 "Department of Medicine, University of California San Francisco; San Francisco, CA, USA."), [Nevan J Krogan](https://pubmed.ncbi.nlm.nih.gov/?term=Krogan+NJ&cauthor_id=42758812)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#full-view-affiliation-1 "J. David Gladstone Institutes; San Francisco, CA, USA.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#full-view-affiliation-4 "Department of Bioengineering and Therapeutic Sciences, University of California San Francisco; San Francisco, CA, USA.")[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#full-view-affiliation-5 "Quantitative Biosciences Institute \(QBI\), University of California San Francisco; San Francisco, CA, USA."), [Melanie Ott](https://pubmed.ncbi.nlm.nih.gov/?term=Ott+M&cauthor_id=42758812)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#full-view-affiliation-1 "J. David Gladstone Institutes; San Francisco, CA, USA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#full-view-affiliation-2 "Michael Hulton Center for HIV Cure Research at Gladstone; San Francisco, CA, USA.")[ 8 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#full-view-affiliation-8 "Department of Medicine, University of California San Francisco; San Francisco, CA, USA.")[ 9 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#full-view-affiliation-9 "Biohub; San Francisco, CA, USA.") Affiliations Expand ### Affiliations * 1 J. David Gladstone Institutes; San Francisco, CA, USA. * 2 Michael Hulton Center for HIV Cure Research at Gladstone; San Francisco, CA, USA. * 3 Laboratory of Neurological Infections and Immunity, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Rocky Mountain Laboratories; Hamilton, MT, USA. * 4 Department of Bioengineering and Therapeutic Sciences, University of California San Francisco; San Francisco, CA, USA. * 5 Quantitative Biosciences Institute (QBI), University of California San Francisco; San Francisco, CA, USA. * 6 Cardiovascular Research Institute, University of California San Francisco; San Francisco, CA, USA. * 7 Department of Anesthesia, University of California San Francisco; San Francisco, CA, USA. * 8 Department of Medicine, University of California San Francisco; San Francisco, CA, USA. * 9 Biohub; San Francisco, CA, USA. * PMID: **42758812** * DOI: [ 10.1126/sciadv.aee5421 ](https://doi.org/10.1126/sciadv.aee5421) Item in Clipboard # Secreted ORF8 reprograms macrophages to enhance SARS-CoV-2 infection of lung epithelial cells Yusuke Matsui et al. Sci Adv. 2026. Show details Display options Display options Format Abstract PubMed PMID Sci Adv Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Sci+Adv%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Sci+Adv%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42758812/) . 2026 Sep 18;12(38):eaee5421. doi: 10.1126/sciadv.aee5421. Epub 2026 Sep 18. ### Authors [Yusuke Matsui](https://pubmed.ncbi.nlm.nih.gov/?term=Matsui+Y&cauthor_id=42758812)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#short-view-affiliation-1 "J. David Gladstone Institutes; San Francisco, CA, USA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#short-view-affiliation-2 "Michael Hulton Center for HIV Cure Research at Gladstone; San Francisco, CA, USA."), [Rahul K Suryawanshi](https://pubmed.ncbi.nlm.nih.gov/?term=Suryawanshi+RK&cauthor_id=42758812)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#short-view-affiliation-3 "Laboratory of Neurological Infections and Immunity, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Rocky Mountain Laboratories; Hamilton, MT, USA."), [Mauricio Montano](https://pubmed.ncbi.nlm.nih.gov/?term=Montano+M&cauthor_id=42758812)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#short-view-affiliation-1 "J. David Gladstone Institutes; San Francisco, CA, USA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#short-view-affiliation-2 "Michael Hulton Center for HIV Cure Research at Gladstone; San Francisco, CA, USA."), [Taha Y Taha](https://pubmed.ncbi.nlm.nih.gov/?term=Taha+TY&cauthor_id=42758812)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#short-view-affiliation-1 "J. David Gladstone Institutes; San Francisco, CA, USA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#short-view-affiliation-2 "Michael Hulton Center for HIV Cure Research at Gladstone; San Francisco, CA, USA.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#short-view-affiliation-4 "Department of Bioengineering and Therapeutic Sciences, University of California San Francisco; San Francisco, CA, USA."), [Mir M Khalid](https://pubmed.ncbi.nlm.nih.gov/?term=Khalid+MM&cauthor_id=42758812)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#short-view-affiliation-1 "J. David Gladstone Institutes; San Francisco, CA, USA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#short-view-affiliation-2 "Michael Hulton Center for HIV Cure Research at Gladstone; San Francisco, CA, USA."), [Limeng Sun](https://pubmed.ncbi.nlm.nih.gov/?term=Sun+L&cauthor_id=42758812)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#short-view-affiliation-1 "J. David Gladstone Institutes; San Francisco, CA, USA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#short-view-affiliation-2 "Michael Hulton Center for HIV Cure Research at Gladstone; San Francisco, CA, USA."), [Kanika Khanna](https://pubmed.ncbi.nlm.nih.gov/?term=Khanna+K&cauthor_id=42758812)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#short-view-affiliation-1 "J. David Gladstone Institutes; San Francisco, CA, USA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#short-view-affiliation-2 "Michael Hulton Center for HIV Cure Research at Gladstone; San Francisco, CA, USA."), [Jin Tang](https://pubmed.ncbi.nlm.nih.gov/?term=Tang+J&cauthor_id=42758812)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#short-view-affiliation-1 "J. David Gladstone Institutes; San Francisco, CA, USA.")[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#short-view-affiliation-5 "Quantitative Biosciences Institute \(QBI\), University of California San Francisco; San Francisco, CA, USA."), [Yuan Zhou](https://pubmed.ncbi.nlm.nih.gov/?term=Zhou+Y&cauthor_id=42758812)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#short-view-affiliation-1 "J. David Gladstone Institutes; San Francisco, CA, USA.")[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#short-view-affiliation-5 "Quantitative Biosciences Institute \(QBI\), University of California San Francisco; San Francisco, CA, USA."), [Robyn M Kaake](https://pubmed.ncbi.nlm.nih.gov/?term=Kaake+RM&cauthor_id=42758812)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#short-view-affiliation-1 "J. David Gladstone Institutes; San Francisco, CA, USA.")[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#short-view-affiliation-5 "Quantitative Biosciences Institute \(QBI\), University of California San Francisco; San Francisco, CA, USA."), [Xiaohui Fang](https://pubmed.ncbi.nlm.nih.gov/?term=Fang+X&cauthor_id=42758812)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#short-view-affiliation-6 "Cardiovascular Research Institute, University of California San Francisco; San Francisco, CA, USA."), [Mazharul Maishan](https://pubmed.ncbi.nlm.nih.gov/?term=Maishan+M&cauthor_id=42758812)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#short-view-affiliation-6 "Cardiovascular Research Institute, University of California San Francisco; San Francisco, CA, USA."), [Michael A Matthay](https://pubmed.ncbi.nlm.nih.gov/?term=Matthay+MA&cauthor_id=42758812)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#short-view-affiliation-6 "Cardiovascular Research Institute, University of California San Francisco; San Francisco, CA, USA.")[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#short-view-affiliation-7 "Department of Anesthesia, University of California San Francisco; San Francisco, CA, USA.")[ 8 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#short-view-affiliation-8 "Department of Medicine, University of California San Francisco; San Francisco, CA, USA."), [Nevan J Krogan](https://pubmed.ncbi.nlm.nih.gov/?term=Krogan+NJ&cauthor_id=42758812)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#short-view-affiliation-1 "J. David Gladstone Institutes; San Francisco, CA, USA.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#short-view-affiliation-4 "Department of Bioengineering and Therapeutic Sciences, University of California San Francisco; San Francisco, CA, USA.")[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#short-view-affiliation-5 "Quantitative Biosciences Institute \(QBI\), University of California San Francisco; San Francisco, CA, USA."), [Melanie Ott](https://pubmed.ncbi.nlm.nih.gov/?term=Ott+M&cauthor_id=42758812)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#short-view-affiliation-1 "J. David Gladstone Institutes; San Francisco, CA, USA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#short-view-affiliation-2 "Michael Hulton Center for HIV Cure Research at Gladstone; San Francisco, CA, USA.")[ 8 ](https://pubmed.ncbi.nlm.nih.gov/42758812/#short-view-affiliation-8 "Department of Medicine, University of Californ
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