0000000000162056
AUTHOR
Kai A. Kropp
Enhancerless Cytomegalovirus Is Capable of Establishing a Low-Level Maintenance Infection in Severely Immunodeficient Host Tissues but Fails in Exponential Growth
ABSTRACT Major immediate-early transcriptional enhancers are genetic control elements that act, through docking with host transcription factors, as a decisive regulatory unit for efficient initiation of the productive virus cycle. Animal models are required for studying the function of enhancers paradigmatically in host organs. Here, we have sought to quantitatively assess the establishment, maintenance, and level of in vivo growth of enhancerless mutants of murine cytomegalovirus in comparison with those of an enhancer-bearing counterpart in models of the immunocompromised or immunologically immature host. Evidence is presented showing that enhancerless viruses are capable of forming restr…
Synergism between the components of the bipartite major immediate-early transcriptional enhancer of murine cytomegalovirus does not accelerate virus replication in cell culture and host tissues
Major immediate-early (MIE) transcriptional enhancers of cytomegaloviruses are key regulators that are regarded as determinants of virus replicative fitness and pathogenicity. The MIE locus of murine cytomegalovirus (mCMV) shows bidirectional gene-pair architecture, with a bipartite enhancer flanked by divergent core promoters. Here, we have constructed recombinant viruses mCMV-ΔEnh1 and mCMV-ΔEnh2 to study the impact of either enhancer component on bidirectional MIE gene transcription and on virus replication in cell culture and various host tissues that are relevant to CMV disease. The data revealed that the two unipartite enhancers can operate independently, but synergize in enhancing MI…
CD8 T-Cell Immunotherapy of Cytomegalovirus Disease in the Murine Model
Publisher Summary Cytomegaloviruses (CMVs) are conditional pathogens that are strictly species specific and are usually well controlled in their respective mammalian hosts by the effector mechanisms of both innate and adaptive immunity. Human CMV (hCMV) is mostly acquired perinatally as well as in early childhood and is transmitted, for instance, through breast milk and saliva. Whilst the immune response in an immunocompetent host prevents an overt CMV disease and rapidly terminates the productive acute infection, viral genome is maintained in most tissues for the life span of the infected host in a state known as viral latency. Latency implies that infectious virions are no longer produced…