Biology Reference
In-Depth Information
Virus Entry and Innate Immune Activation
M. K. Isaacson , L. K. Juckem , T. Compton ( ΓΌ )
Contents
Introduction to Virus Entry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86
Cellular Receptors Proposed for HCMV Entry. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86
Envelope and Membrane Fusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
Introduction to Activation of Innate Immunity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
Activation of Inflammatory Cytokines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
Activation of Interferon Responses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
Coordination of Entry Events and Innate Immune Activation Steps . . . . . . . . . . . . . . . . . . . . 94
Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
Abstract Human cytomegalovirus (HCMV) exhibits an exceptionally broad
cellular tropism as it is capable of infecting most major organ systems and
cell types. Definitive proof of an essential role for a cellular molecule that
serves as an entry receptor has proven very challenging. It is widely hypoth-
esized that receptor utilization, envelope glycoprotein requirements and entry
pathways may all vary according to cell type, which is partially supported
by the data. What has clearly emerged in recent years is that virus entry
is not going undetected by the host. Robust and rapid induction of innate
immune response is intimately associated with entry-related events. Here we
review the state of knowledge on HCMV cellular entry mediators confronting
the scientific challenges by accruing a definitive data set. We also review the
roles of pattern recognition receptors such as Toll-like receptors in activation
of specific innate immune response and discuss how entry events are tightly
coordinated with innate immune initiation steps.
T. Compton
Infectious Diseases , Novartis Institutes for Biomedical Research, Cambridge , MA 02139 , USA
teresa.compton@novartis.com
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