Poxvirus is a major virus group of potential bioterrorism and emerging infectious agents. On top of the list is Variola major virus that is known to be the causative agent of the deadly disease smallpox [Slifka & Hanifin, 2004]. Smallpox has a very high mortality and morbidity and the viral agent can be weaponized [Gooze & Hughes, 2003]. Monkeypox virus is another virus that has caused the 2003 outbreak in the US [Lewis-Jones, 2004]. Poxvirus has a complicated replication cycle (Figure below). There are three infectious forms of poxvirus: mature virus (MV, aka IMV), wrapped virus (WV, aka IEV), and extracellular virus (EV, aka EEV). Both MV and EV can enter the cells by binding and fusion with the cell plasma membrane [Moss, 2006]. After uncoating, early genes are transcribed, and most of the products function to support viral DNA replication and modulate cellular functions. Products of intermediate genes tend to modulate intracellular functions. At the later stage, gene products are produce to assemble virus particles in the factory for virus production. Poxvirus has a genome that contains over 200 ORFs, with some differences in different species.
Vaccines and antiviral drugs are the two direct approaches to control a poxvirus outbreak. There are a number of vital processes that may be targeted for intervention to treat or prevent a poxvirus infection. Surface proteins of poxvirus are the major targets for vaccine development. Vaccinia virus was developed as the conventional vaccine for smallpox and recently more attenuated strains were developed to improve the safety and effectiveness of the vaccine [Arita, 2005]. One of the strains is called modified virus Ankara (MVA) and its efficacy is very promising [Phelps et al., 2007]. A further improvement of the MVA is to introduce murine granulocyte-macrophage colony-stimulating factor (mGM-CSF), human CCL20/human macrophage inflammatory protein 3alpha (hCCL20/hMIP-3alpha), or human fms-like tyrosine kinase 3 ligand (hFlt3-L), factors in a recombinant MVA, which may result in an enhanced immunity [Chavan et al., 2006]. Understanding of the interaction of poxvirus with the host cells that are directly infected and the immune system will greatly improve the design for a safer, more effective vaccine against a broader spectrum of poxviruses. In case of anti-poxvirus drugs, a number of strategies are currently under investigation, with most of the virus-targeted inhibitors (some inhibit host enzymes) directed to the DNA replication enzymes such as DNA polymerase [Prichard & Kern, 2005; De Clercq, 2001]. These inhibitors are nucleoside analogs which were previously shown to be antiherpes virus or other antiviral agents. When tested against vaccinia and cowpox virus infection, they also showed significant antiviral activities. Efforts on design of novel antivirals against poxvirus are in progress.