Rhesus CMV: An emerging animal model for human CMV

Colin Powers, Klaus Frueh

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

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 different CMV strains has been observed despite a strong immune response. Long-term immune stimulation by CMV has also been implicated in immune senescence and chronic conditions such as atherosclerosis. CMVs are highly species-specific 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.

Original languageEnglish (US)
Pages (from-to)109-115
Number of pages7
JournalMedical Microbiology and Immunology
Volume197
Issue number2
DOIs
StatePublished - Jun 2008

Fingerprint

Animal Models
SCID Mice
Pan troglodytes
Infection
Inbred NOD Mouse
Viral Genome
Macaca mulatta
Genes
Immune System
Rodentia
Atherosclerosis
Guinea Pigs
Acquired Immunodeficiency Syndrome
Genome
Viruses
Antigens
Costs and Cost Analysis

Keywords

  • CMV
  • Cytomegalovirus
  • Cytomegalovirus animal models
  • Rhesus CMV
  • Rhesus cytomegalovirus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Microbiology (medical)
  • Immunology

Cite this

Rhesus CMV : An emerging animal model for human CMV. / Powers, Colin; Frueh, Klaus.

In: Medical Microbiology and Immunology, Vol. 197, No. 2, 06.2008, p. 109-115.

Research output: Contribution to journalArticle

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abstract = "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 different CMV strains has been observed despite a strong immune response. Long-term immune stimulation by CMV has also been implicated in immune senescence and chronic conditions such as atherosclerosis. CMVs are highly species-specific 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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