Pathogenetic consequences of cytomegalovirus-host co-evolution

Abenes, Gerardo; Liu, Fenyong

doi:10.1007/s12250-008-3003-2

Cited by 1 publication

(1 citation statement)

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“…This continued virus-host co-evolution has resulted in the acquisition of a series of host-specific genes, which benefit the virus. A number of these genes have augmented viral replication capacity; and the acquisition of anti-apoptotic and immune-evasion genes appear to evade the host immune response preventing complete elimination of the virus during primary infection [ 19 ]. In addition to human CMV [ 20 – 24 ], cytomegaloviruses have been isolated and characterized from a number of different non-human primate (NHP) species, including but not limited to, chimpanzees [ 25 , 26 ], rhesus macaques [ 27 , 28 ], cynomolgus macaques [ 29 , 30 ] as well as more distant species involving guinea pigs [ 31 , 32 ], mice [ 33 ], rats [ 34 ], and tree shrews [ 35 ], among others.…”

Section: Introductionmentioning

confidence: 99%

Examining the Species-Specificity of Rhesus Macaque Cytomegalovirus (RhCMV) in Cynomolgus Macaques

et al. 2015

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Cytomegalovirus (CMV) is a highly species-specific virus that has co-evolved with its host over millions of years and thus restricting cross-species infection. To examine the extent to which host restriction may prevent cross-species research between closely related non-human primates, we evaluated experimental infection of cynomolgus macaques with a recombinant rhesus macaque-derived CMV (RhCMV-eGFP). Twelve cynomolgus macaques were randomly allocated to three groups: one experimental group (RhCMV-eGFP) and two control groups (UV-inactivated RhCMV-eGFP or media alone). The animals were given two subcutaneous inoculations at week 0 and week 8, and a subset of animals received an intravenous inoculation at week 23. No overt clinical or haematological changes were observed and PBMCs isolated from RhCMV-eGFP inoculated animals had comparable eGFP- and IE-1-specific cellular responses to the control animals. Following inoculation with RhCMV-eGFP, we were unable to detect evidence of infection in any blood or tissue samples up to 4 years post-inoculation, using sensitive viral co-culture, qPCR, and Western blot assays. Co-culture of urine and saliva samples demonstrated the presence of endogenous cynomolgus CMV (CyCMV) cytopathic effect, however no concomitant eGFP expression was observed. The absence of detectable RhCMV-eGFP suggests that the CyCMV-seropositive cynomolgus macaques were not productively infected with RhCMV-eGFP under these inoculation conditions. In a continued effort to develop CMV as a viral vector for an HIV/SIV vaccine, these studies demonstrate that CMV is highly restricted to its host species and can be highly affected by laboratory cell culture. Consideration of the differences between lab-adapted and primary viruses with respect to species range and cell tropism should be a priority in evaluating CMV as vaccine vector for HIV or other pathogens at the preclinical development stage.

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