Journal Article

SARS-CoV-2 ORF8 modulates lung inflammation and clinical disease progression

Baracco, Lauren, Taylor, Louis, Hart, Rebecca, Dillen, Carly, Kim, Raymond, Assad-Garcia, Nacyra, Vashee, Sanjay, Gonzalez-Juarbe, Norberto, Frieman, Matthew B., Xue, Yong, Ardanuy, Jeremy, McGrath, Marisa E.

2024

Overview

The virus severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, is the causative agent of the current COVID-19 pandemic. It possesses a large 30 kilobase (kb) genome that encodes structural, non-structural, and accessory proteins. Although not necessary to cause disease, these accessory proteins are known to influence viral replication and pathogenesis. Through the synthesis of novel infectious clones of SARS-CoV-2 that lack one or more of the accessory proteins of the virus, we have found that one of these accessory proteins, ORF8, is critical for the modulation of the host inflammatory response. Mice infected with a SARS-CoV-2 virus lacking ORF8 exhibit increased weight loss and exacerbated macrophage infiltration into the lungs. Additionally, infection of mice with recombinant SARS-CoV-2 viruses encoding ORF8 mutations found in variants of concern reveal that naturally occurring mutations in this protein influence disease severity. Our studies with a virus lacking this ORF8 protein and viruses possessing naturally occurring point mutations in this protein demonstrate that this protein impacts pathogenesis.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Animals / Biology and life sciences / Care and treatment / China / Chlorocebus aethiops / Cloning / Coronaviruses / COVID-19 / COVID-19 - genetics / COVID-19 - immunology / COVID-19 - pathology / COVID-19 - virology / Development and progression / Diagnosis / Disease Progression / E coli / Epidemics / Female / Gene mutations / Genomes / Genomics / Health aspects / Humans / Inflammation / Inflammatory response / Lung - pathology / Lung - virology / Lungs / Macrophages / Maryland / Massachusetts / Medical research / Medicine and health sciences / Medicine, Experimental / Mice / Mutation / Pandemics / Pathogenesis / Penicillin / Plasmids / Pneumonia / Pneumonia - pathology / Pneumonia - virology / Proteins / Research and Analysis Methods / Respiratory diseases / Risk factors / SARS-CoV-2 - genetics / Severe acute respiratory syndrome / Severe acute respiratory syndrome coronavirus 2 / Vero Cells / Viral diseases / Viral pneumonia / Viral Proteins - genetics / Viral Proteins - metabolism / Virus Replication / Viruses / Weight loss