Biology Reference
In-Depth Information
The practical impact of cell tropism issues may concern the design of cytomegalo-
virus vaccines. Given the limited success of vaccination with the highly adapted strain
Towne, it appears as if a higher level of replication within the vaccinee is necessary for
induction of a more robust immune response. Therefore, a more moderate attenuation
with partial preservation of endothelial and epithelial cell tropism may be desirable.
The introduction of small nonlethal mutations within known tropism genes is one
possible approach to achieve such intermediate phenotypes.
Finally, an exact definition of entry pathways in diverse cell types may allow for
the development of novel antiviral intervention strategies. At present, all anti-CMV
chemotherapies target viral DNA replication. By analogy to HIV, entry inhibitors
may complement the available drugs and allow for synergistic effects in combination
therapies. Such an approach should certainly consider the possibility of different
entry pathways in major target cell types such as fibroblasts and endothelial cells.
Acknowledgements
This work was supported by the German research foundation (DFG SI
779/3-2).
References
Adler B, Scrivano L, Ruzcics Z, Rupp B, Sinzger C, Koszinowski U (2006) Role of human
cytomegalovirus UL131A in cell type-specific virus entry and release. J Gen Virol
87:2451-2460
Albrecht T, Weller TH (1980) Heterogeneous morphologic features of plaques induced by five
strains of human cytomegalovirus. Am J Clin Pathol 73:648-654
Balazs M (1984) Electron microscopic examination of congenital cytomegalovirus hepatitis.
Virchows Arch A Pathol Anat Histopathol 405:119-129
Baldanti F, Paolucci S, Campanini G, Sarasini A, Percivalle E, Revello MG, Gerna G (2006)
Human cytomegalovirus UL131A, UL130 and UL128 genes are highly conserved among field
isolates. Arch Virol 151:1225-1233
Bissinger AL, Sinzger C, Kaiserling E, Jahn G (2002) Human cytomegalovirus as a direct patho-
gen: correlation of multiorgan involvement and cell distribution with clinical and pathological
findings in a case of congenital inclusion disease. J Med Virol 67:200-206
Bissinger AL, Oettle H, Jahn G, Neuhaus P, Sinzger C (2004) Cytomegalovirus infection after
orthotopic liver transplantation is restricted by a pre-existing antiviral immune response of the
recipient. J Med Virol 73:45-53
Bodaghi B, Slobbe-van Drunen ME, Topilko A, Perret E, Vossen RC, van Dam-Mieras MC,
Zipeto D, Virelizier JL, LeHoang P, Bruggeman CA, Michelson S (1999) Entry of human
cytomegalovirus into retinal pigment epithelial and endothelial cells by endocytosis. Invest
Ophthalmol Vis Sci 40:2598-2607
Brune W, Menard C, Heesemann J, Koszinowski UH (2001) A ribonucleotide reductase homolog
of cytomegalovirus and endothelial cell tropism. Science 291:303-305
Digel M, Sinzger C (2006) Determinants of endothelial cell tropism of human cytomegalovirus.
In: Reddehase MJ (ed) Cytomegaloviruses: molecular biology and immunology. Caister
Academic Press, Norfolk, pp 445-464
Donnellan WL, Chantra-Umporn S, Kidd JM (1966) The cytomegalic inclusion cell. An electron
microscopic study. Arch Pathol 82:336-348
Dunn W, Chou C, Li H, Hai R, Patterson D, Stolc V, Zhu H, Liu F (2003) Functional profiling of
a human cytomegalovirus genome. Proc Natl Acad Sci USA 100:14223-14228
