Mouse Cytomegalovirus Crosses the Species Barrier with Help from a Few Human Cytomegalovirus Proteins

Abstract

Strong species specificity and similar tropisms suggest mouse cytomegalovirus (mCMV) as a potential vector for transgenes into human cells. We reexamined the dogma that mouse cytomegalovirus cannot productively replicate in human cells and found that mouse cytomegalovirus can produce infectious particles albeit at a level that does not sustain an infection. This finding demonstrates that mouse cytomegalovirus can undergo all processes of its life cycle in human cells but may not be well adapted to circumvent the human cell's intrinsic defenses. The suppression of mCMV production in human cells is affected at several levels, which additively or synergistically result in the appearance of species specificity. Hydrolysis of most newly replicated viral DNA and very low capsid protein transcription reduced the potential particle production to insignificant levels. These effects can be ameliorated by adding human cytomegalovirus tegument proteins and immediate-early protein 1. They function synergistically to produce significant amounts of mCMV in human cells. While the possibility that mouse cytomegalovirus might replicate in human cells raises caution in the use of this virus as a transgene vector, manipulation of the mouse cytomegalovirus genome to allow limited spread to other human cells might also provide an advantage for the distribution of certain transgenic products.