US28: HCMV's Swiss Army Knife

Viruses. 2018 Aug 20;10(8):445. doi: 10.3390/v10080445.


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.

Keywords: HCMV; US28; cytomegalovirus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cardiovascular Diseases / pathology
  • Cardiovascular Diseases / virology*
  • Cytomegalovirus / genetics
  • Cytomegalovirus / metabolism
  • Cytomegalovirus / pathogenicity*
  • Cytomegalovirus Infections / drug therapy
  • Cytomegalovirus Infections / pathology
  • Cytomegalovirus Infections / virology*
  • Gene Expression Regulation, Viral*
  • Host-Pathogen Interactions*
  • Humans
  • Models, Molecular
  • Neoplasms / pathology
  • Neoplasms / virology*
  • Protein Structure, Secondary
  • Receptors, Chemokine / genetics*
  • Receptors, Chemokine / therapeutic use
  • Signal Transduction
  • Viral Proteins / genetics*
  • Viral Proteins / therapeutic use
  • Virus Latency / genetics
  • Virus Replication / genetics


  • Receptors, Chemokine
  • US28 receptor, Cytomegalovirus
  • Viral Proteins