Research Article:


Cross-Species Rhesus Cytomegalovirus Infection of Cynomolgus Macaques

Angie K Marsh, Aruna P Ambagala, Catia T Perciani, Justen Russell, Jacqueline K Chan, Michelle Janes, Joseph M Antony, Richard Pilon, Paul Sandstrom, David O Willer, Kelly S MacDonald




PLOS one

Scientific Abstract

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.

Lay Abstract

This is a study about transmission of a virus between two different species of monkeys.

Most (maybe all) primates have their own form of the virus CMV, humans included. More than half of you reading this are probably infected, and don’t even know it. Once infected, CMV hangs around for life. Thankfully, it is (usually) asymptomatic. Of course, infection with one strain does not protect you from being infected with a second (or third)

We attempt to see whether a strain of the virus isolated from one species of macaque monkeys could infect a second, closely related species.

Thanks to a later study by Burwitz et al. we now know why this one strain was not able to cross the species barrier, and what is required for a CMV strain to spread.