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US28: HCMV's Swiss Army Knife
Benjamin A Krishna1, William E Miller2, Christine M O'Connor3
1Genomic Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA. krishnb2@ccf.org.
Abstract:
US28 is one of four G protein coupled receptors (GPCRs) encoded by human cytomegalovirus (HCMV). The US28 protein (pUS28) is a potent signaling molecule that alters a variety of cellular pathways that ultimately alter the host cell environment. This viral GPCR is expressed not only in the context of lytic replication but also during viral latency, highlighting its multifunctional properties. pUS28 is a functional GPCR, and its manipulation of multiple signaling pathways likely impacts HCMV pathogenesis. Herein, we will discuss the impact of pUS28 on both lytic and latent infection, pUS28-mediated signaling and its downstream consequences, and the influence this viral GPCR may have on disease states, including cardiovascular disease and cancer. We will also discuss the potential for and progress towards exploiting pUS28 as a novel therapeutic to combat HCMV.
Insights
Human cytomegalovirus (HCMV) US28 protein impacts viral infection and host cells. This viral G protein coupled receptor (GPCR) shows therapeutic potential for treating HCMV-related diseases.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Human cytomegalovirus (HCMV) encodes four G protein coupled receptors (GPCRs).
- The viral US28 protein (pUS28) is a potent signaling molecule affecting host cell pathways.
- pUS28 expression occurs during both lytic and latent HCMV infection, indicating diverse roles.
Purpose of the Study:
- To discuss the impact of pUS28 on lytic and latent HCMV infection.
- To explore pUS28-mediated signaling pathways and their consequences.
- To examine pUS28's influence on disease states and its therapeutic potential.
Main Methods:
- Review of existing literature on pUS28 function and signaling.
- Analysis of pUS28's role in viral pathogenesis.
- Discussion of pUS28's involvement in cardiovascular disease and cancer.
Main Results:
- pUS28 significantly alters host cell pathways, impacting viral replication and latency.
- pUS28 signaling influences HCMV pathogenesis and associated diseases.
- pUS28 demonstrates potential as a therapeutic target against HCMV.
Conclusions:
- pUS28 is a multifunctional viral GPCR critical for HCMV infection.
- Understanding pUS28's signaling is key to combating HCMV-related diseases.
- Targeting pUS28 offers a promising strategy for novel antiviral therapies.