Nka. Grzimek et al., In vivo replication of recombinant murine cytomegalovirus driven by the paralogous major immediate-early promoter-enhancer of human cytomegalovirus, J VIROLOGY, 73(6), 1999, pp. 5043-5055
Transcription of the major immediate-early (MIE) genes of cytomegaloviruses
(CMV) is driven by a strong promoter-enhancer (MIEPE) complex. Transactiva
tor proteins encoded by these MIE genes are essential for productive infect
ion. Accordingly, the MIEPE is a crucial control point, and its regulation
by activators and repressors is pertinent to virus replication. Since the M
IEPE contains multiple regulatory elements, it was reasonable to assume tha
t specific sequence motifs are irreplaceable for specifying the cell-type t
ropism and replication pattern. Recent work on murine CMV infectivity (A. A
ngulo, M. Messerle, U. H. Koszinowski, and P. Ghazal, J. Virol. 72:8502-850
9, 1998) has documented the proposed enhancing function of the enhancer in
that its resection or its replacement by a nonregulatory stuffer sequence r
esulted in a significant reduction of infectivity, even though replication
competence was maintained by a basal activity of the spared authentic MIE p
romoter. Notably, full capacity for productive in vitro infection of fibrob
lasts was restored in recombinant viruses by the human CMV enhancer. Using
two-color in situ hybridization with MIEPE-specific polynucleotide probes,
we demonstrated that a murine CMV recombinant in which the complete murine
CMV MIEPE is replaced by the paralogous human CMV core promoter and enhance
r (recombinant virus mCMVhMIEPE) retained the potential to replicate in viv
o in all tissues relevant to CMV disease. Notably, mCMVhMIEPE was also foun
d to replicate in the liver, a site at which transgenic hCMV MIEPE is silen
ced. We conclude that productive in vivo infection with murine CMV does not
strictly depend on a MIEPE type-specific regulation.