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Study uncovers mechanisms necessary for SARS-CoV-2 infection in macrophages

Therapeutic strategies that specifically target this process might prove useful in alleviating severity of disease

Date:
October 24, 2022
Source:
Boston University School of Medicine
Summary:
Researchers have identified a receptor, CD169 (also called Siglec1), that is exclusively expressed on macrophages and contributes to the hyper-inflammatory response of macrophages upon infection with SARS-CoV-2. These findings, they believe, may provide an explanation of how SARS-CoV-2 infection of macrophages in lungs of COVID-19 patients promote inflammatory responses.
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Dysregulation of macrophages during SARS-CoV-2 infection and the over-exuberant production of pro-inflammatory cytokines by these macrophages has been hypothesized to contribute to severity of COVID-19 disease. However, the mechanisms that contribute to the hyper-inflammatory response of macrophages has remained unclear.

Now, researchers from Boston University Chobanian & Avedisian School of Medicine have identified a receptor, CD169 (also called Siglec1), that is exclusively expressed on macrophages and contributes to the hyper-inflammatory response of macrophages upon infection with SARS-CoV-2. These findings, they believe, may provide an explanation of how SARS-CoV-2 infection of macrophages in lungs of COVID-19 patients promote inflammatory responses.

"These macrophages do not express ACE2, the SARS-CoV-2 receptor. Rather SARS-CoV-2 entry in macrophages was facilitated by a lectin, CD169, which recognizes the spike protein of SARS-CoV-2," explained corresponding author Suryaram Gummuluru, PhD, professor of microbiology.

To test their theory, the researchers compared human macrophages that expressed CD169 and those that did not, and then exposed these cells to SARS-CoV-2. "We found that macrophages expressing CD169 were highly permissive for viral entry and initiation of virus replication, but completion of the viral life cycle was blocked and prevented production of new infectious virus particles. Surprisingly, initiation of virus replication and expression of abortive viral transcripts in CD169+ macrophages, was sufficient to activate host surveillance mechanisms (innate immune response) and induce expression of pro-inflammatory responses," said Gummuluru.

The researchers hypothesize that persistent activation of viral sensing mechanisms that detect these viral replication intermediates in macrophages might contribute to aberrant inflammation associated with severe COVID-19 disease.

According to the researchers, future studies are needed to address the molecular details of this unique virus entry mechanism and the restricted virus replication in macrophages, and how this entry mechanism differs from the conventional ACE2-mediated entry pathway. "Importantly, consideration of therapies that target this alternative virus entry mechanism are needed, as they might prove useful in ameliorating the harmful effects of SARS-CoV-2 infection in macrophages," he adds.

These findings appear online in the journal in PLoS Pathogens.

Funding for this study was provided by NIH grants R01AI064099 1041 (SG), R01DA051889 (SG), R01AG060890 (SG), P30AI042853 (SG), R01CA2 27292 1042 (ST), R01AI106036 (YB and ST), R01AI133486 (EM), and R21AI135912 (EM) as well 1043 as Fast Grants (EM) and Evergrande MassCPR (EM).


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Materials provided by Boston University School of Medicine. Note: Content may be edited for style and length.


Journal Reference:

  1. Sallieu Jalloh, Judith Olejnik, Jacob Berrigan, Annuurun Nisa, Ellen L. Suder, Hisashi Akiyama, Maohua Lei, Sita Ramaswamy, Sanjay Tyagi, Yuri Bushkin, Elke Mühlberger, Suryaram Gummuluru. CD169-mediated restrictive SARS-CoV-2 infection of macrophages induces pro-inflammatory responses. PLOS Pathogens, 2022; 18 (10): e1010479 DOI: 10.1371/journal.ppat.1010479

Cite This Page:

Boston University School of Medicine. "Study uncovers mechanisms necessary for SARS-CoV-2 infection in macrophages." ScienceDaily. ScienceDaily, 24 October 2022. <www.sciencedaily.com/releases/2022/10/221024153619.htm>.
Boston University School of Medicine. (2022, October 24). Study uncovers mechanisms necessary for SARS-CoV-2 infection in macrophages. ScienceDaily. Retrieved October 14, 2024 from www.sciencedaily.com/releases/2022/10/221024153619.htm
Boston University School of Medicine. "Study uncovers mechanisms necessary for SARS-CoV-2 infection in macrophages." ScienceDaily. www.sciencedaily.com/releases/2022/10/221024153619.htm (accessed October 14, 2024).

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