Mouse models of cytomegalovirus latency: overview.

BACKGROUND

The molecular regulation of viral latency and reactivation is a central unsolved issue in the understanding of cytomegalovirus (CMV) biology. Like human CMV (hCMV), murine CMV (mCMV) can establish a latent infection in cells of the myeloid lineage. Since mCMV genome remains present in various organs after its clearance from hematopoietic cells first in bone marrow and much later in blood, there must exist one or more widely distributed cell type(s) representing the cellular site(s) of enduring mCMV latency in host tissues. Endothelial cells and histiocytes are candidates, but the question is not yet settled. Another long debated problem appears to be solved: mCMV establishes true molecular latency rather than a low-level persistence of productive infection. This conclusion is based on two recent advances. First, on a highly improved assay of infectivity, and second, on very sensitive RT PCRs for detecting viral transcripts during latency. In essence, infectious virus and productive cycle transcripts, such as transcripts of early-phase gene M55 (gB) and ie3 transcripts specifying the essential transactivator protein IE3, were found to be absent during mCMV latency in the lungs.

OBJECTIVES

We will here review recent data on the variegated expression of IE-phase genes ie1 and ie2 during mCMV latency in the lungs, and on the expression patterns found in transcriptional foci during induced reactivation. We will discuss immunological implications of ie1 gene expression during latency and will speculate a bit on how CD8 T cells might trigger latency-associated ie1 gene expression in a regulatory circuit.