Characterization of the Rhesus Cytomegalovirus US28 Locus

Penfold, Mark E.T.; Schmidt, Thorsten; Dairaghi, Daniel J.; Barry, Peter A.; Schall, Thomas J.

doi:10.1128/jvi.77.19.10404-10413.2003

Cited by 44 publications

(29 citation statements)

References 51 publications

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“…RhCMV contains Wve homologs to the HCMV chemokine receptor US28, a unique seven-transmembrane domain gene family not found in rodent CMVs. One of these, RhUS28.5, has been shown to have a similar ligand binding proWle as HCMV US28 [62]. The US12 gene family, another seventransmembrane domain gene family found only in primate CMVs, is also well conserved in RhCMV [63].…”

Section: Functional Characterizations Of Rhcmv Proteinsmentioning

confidence: 99%

Rhesus CMV: an emerging animal model for human CMV

Powers

Früh

2008

Med Microbiol Immunol

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Human CMV is the predominant infectious cause of congenital birth defects and an opportunistic pathogen in immunosuppressed individuals, including AIDS patients. Most individuals are infected early during their life followed by life-long latent infection. During this latent phase, frequent reactivation and antigen production continue to stimulate the immune system. While the immune response is able to control the virus, it is unable to eradicate it. Moreover, super-infection by diVerent CMV strains has been observed despite a strong immune response. Longterm immune stimulation by CMV has also been implicated in immune senescence and chronic conditions such as atherosclerosis. CMVs are highly species-speciWc and the relatedness of CMV genomes exactly mirrors the relatedness of their hosts. Thus, each CMV species is highly adapted to its respective host species, but is unable to infect other, even closely related hosts. While fascinating from an evolutionary perspective, this host restriction prevents studying HCMV in experimental animals. Exceptions are severely immunocompromised mice, e.g. SCID mice, or SCID/NOD mice, which might allow partial reconstitution of CMV infection in rodents. More practical however, is to study CMVs in their natural host, e.g. murine, rat or guinea pig CMVs. However, while these small animal models have many advantages, such as the availability of inbred animals as well as lower cost, the limited homology of the viral genomes with HCMV limits the functional analysis of homologous gene products. The closest relative to HCMV is chimpanzee CMV (CCMV), but this is not a practical animal model since chimps are a protected species, extremely expensive and of very limited availability. In contrast, rhesus macaques are a more widely used experimental animal species and, while more distant than CCMV, rhesus CMV (RhCMV) contains most of the HCMV gene families thus allowing the study of their role in acute and latent CMV infection. In this review we will discuss the current state of developing RhCMV as a model for HCMV.

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Section: Functional Characterizations Of Rhcmv Proteinsmentioning

confidence: 99%

Rhesus CMV: an emerging animal model for human CMV

Powers

Früh

2008

Med Microbiol Immunol

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“…Including RhUL146 and RhUL147 (rh158), this makes a total of 6 genes with homology to -chemokines encoded by RhCMV. It is unclear why the virus would require six -chemokine genes; however, such gene duplication events have been reported, notably in the case of the RhCMV US28 locus, where only one of the five genes was found to encode a functional receptor (Penfold et al, 2003). Additional studies are ongoing to determine which of these RhCMV genes encode functional chemokines and to discern their role in virus infection in vivo.…”

Section: Role In Infectionmentioning

confidence: 99%

“…Expression of US28 transcripts occurs throughout the infection cycle, at immediate early, early, and late time points (Bodaghi et al, 1998;Zipeto et al, 1999), as well as during latency in THP-1 monocytes (Beisser et al, 2001). Although no homologs of this receptor exist in the genomes of rodent CMVs, five tandem homologs of US28 have been identified in the genome of Rhesus CMV (Penfold et al, 2003). Because US27 and US28 are directly adjacent to one another in the HCMV genome and share 31% sequence identity, there has been some speculation that the two are a result of a gene duplication event.…”

Section: Wwwintechopencommentioning

confidence: 99%

Trojan Horses and Fake Immunity Idols: Molecular Mimicry of Host Immune Mediators by Human Cytomegalovirus

Spencer¹

2012

Herpesviridae - A Look Into This Unique Family of Viruses

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“…So far, the most studied vGPCR is US28 (Vischer et al, 2006a). It presents homology to the CC and CX3C chemokine receptors and was shown to bind CC (CCL2, CCL3, CCL4, CCL5, CCL7, CCL11, CCL13, CCL26, and CCL28), CX3C chemokines (CX3CL1), and the viral chemokine vCXCL2 (Gao and Murphy, 1994;Billstrom et al, 1998;Kledal et al, 1998;Penfold et al, 2003) (Fig. 1).…”

Section: ␤-Herpesvirus-encoded Gpcrsmentioning

confidence: 99%

Herpesvirus-Encoded G Protein-Coupled Receptors as Modulators of Cellular Function

Maussang¹,

Vischer²,

Leurs³

et al. 2009

Molecular Pharmacology

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Human herpesviruses (HHVs) are widespread pathogens involved in proliferative diseases, inflammatory conditions, and cardiovascular diseases. During evolution, homologs of human chemokine receptors were integrated into the HHV genomes. In addition to binding endogenous chemokines, these viral G protein-coupled receptors (vGPCRs) have acquired the ability to signal in a constitutive manner. Ligand-induced and ligandindependent and autocrine and paracrine signaling properties of vGPCRs modify the functions of the expressing cells and lead to transformation and escape from immune surveillance. Furthermore, cross-talk or heterodimerization with endogenous chemokine receptors represent other ways for vGPCRs to modify intracellular signaling and cellular functions. As such, these viral receptors seem to play a prominent role during viral pathogenesis and life cycle and thus represent innovative antiviral therapies.G protein-coupled receptors (GPCRs) are essential mediators of cellular communication. Their cell surface expression allows easy access and activation by their extracellular ligands to initiate intracellular signaling cascades. The physiological role of GPCR activation ranges from gene transcription to cellular migration and proliferation. Besides being activated by their cognitive ligands, GPCRs can signal independently from ligand activation. This so-called constitutive activity is the molecular basis of various pathologies (Smit et al., 2007). It is noteworthy that, during evolution, human herpesviruses (HHV) of the ␤ and ␥ families hijacked human GPCR while coexisting with their host (Brunovskis and Kung, 1995). These viral GPCRs (vGPCRs) show considerable homology to chemokine receptors, which are essential in the development of the hematopoietic system and regulation of cellular homeostasis (Mackay, 2001). In addition, chemokine receptors play a prominent role in cancer development (e.g., by inducing cellular proliferation or by modifying cellular migration patterns), resulting in cancer metastasis (Balkwill, 2004). Although human chemokine receptors require ligand activation to exert a physiological function, most of the vGPCRs show high levels of constitutive activity (Vischer et al., 2006b). As for human GPCRs, the constitutive modulation of signaling pathways by vGPCRs may play a role in the development of HHV-related diseases. As such, these vGPCRs may serve as therapeutic targets for the intervention of viral pathogenesis. ␥-Herpesvirus-Encoded G Protein-Coupled ReceptorsThe Kaposi's sarcoma-associated herpesvirus (KSHV or HHV-8) and the Epstein-Barr virus (EBV or HHV-4) are lymphotropic viruses that are involved in proliferative dis- Article, publication date, and citation information can be found at

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Characterization of the Rhesus Cytomegalovirus US28 Locus

Cited by 44 publications

References 51 publications

Rhesus CMV: an emerging animal model for human CMV

Rhesus CMV: an emerging animal model for human CMV

Trojan Horses and Fake Immunity Idols: Molecular Mimicry of Host Immune Mediators by Human Cytomegalovirus

Herpesvirus-Encoded G Protein-Coupled Receptors as Modulators of Cellular Function

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