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Leaky Scanning

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R stands for...

Rous Sarcoma Virus (RSV) and Cancer

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Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...

Rous Sarcoma Virus (RSV) and Cancer

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RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...

Coronavirus

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Respiratory Syncytial Virus Disease

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Human respiratory syncytial virus (RSV) is a widespread pathogen that primarily targets infants and young children but also poses a serious health risk to elderly and immunocompromised individuals. Belonging to the Pneumoviridae family, RSV is a negative-sense, single-stranded RNA virus within the Pneumovirus genus. Its global health burden is significant, with millions of cases annually resulting in hospitalizations and mortality, particularly in resource-limited settings. Although most...

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Related Experiment Video

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Production of Pseudotyped Particles to Study Highly Pathogenic Coronaviruses in a Biosafety Level 2 Setting

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LRRC15 inhibits SARS-CoV-2 cellular entry in trans.

Jaewon Song¹, Ryan D Chow², Mario A Peña-Hernández^3,4

¹Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, Rhode Island, United States of America.

|October 13, 2022

Summary

Researchers discovered LRRC15 as a novel protein that inhibits SARS-CoV-2 entry. This finding offers new insights into controlling viral infections by identifying a key factor that blocks virus attachment and entry into cells.

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Live Imaging and Quantification of Viral Infection in K18 hACE2 Transgenic Mice Using Reporter-Expressing Recombinant SARS-CoV-2

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Published on: November 5, 2021

Area of Science:

Virology
Cell Biology
Immunology

Background:

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) utilizes the angiotensin-converting enzyme 2 (ACE2) receptor for cellular entry.
While viral entry facilitators are well-studied, cellular factors that inhibit viral entry remain largely unknown.

Purpose of the Study:

To identify novel cellular factors that inhibit SARS-CoV-2 entry.
To characterize the mechanism and physiological role of identified inhibitory factors.

Main Methods:

A surfaceome CRISPR activation screen was employed to identify inhibitory factors.
Direct binding assays were performed to assess the interaction between LRRC15 and the SARS-CoV-2 spike protein receptor-binding domain (RBD).
Analysis of human lung single-cell RNA sequencing data was conducted to determine LRRC15 expression patterns.

Main Results:

Human LRRC15 was identified as an inhibitory attachment factor for SARS-CoV-2.
LRRC15 directly binds to the SARS-CoV-2 spike protein RBD, inhibiting viral entry.
LRRC15 is expressed in lung fibroblasts, particularly pathological fibroblasts in COVID-19 patients, and is not coexpressed with ACE2.
LRRC15 in ACE2-negative cells can inhibit viral entry into ACE2-positive cells in trans.

Conclusions:

LRRC15 acts as a SARS-CoV-2 inhibitory attachment factor, directly blocking viral entry.
The non-coexpression of ACE2 and LRRC15, along with LRRC15's trans-inhibitory function, suggests a protective role in lung physiology.
LRRC15 represents a potential therapeutic target for modulating SARS-CoV-2 infection.