Poxvirus Entry, Assembly and Egress

National Institute Of Allergy And Infectious Diseases

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Abstract

There are two major types of infectious vaccinia virus particles: mature virions (MVs) and enveloped virions (EVs). The MVs, which consist of a DNA-protein core surrounded by a lipoprotein membrane, are assembled in cytoplasmic viral factories and contain about 80 polypeptides. A subpopulation of MVs is wrapped by modified trans-Golgi or endosomal cisterna containing additional viral membrane proteins, transported along microtubules to the cell periphery, and exits the cell through the plasma membrane. The EVs are essentially MVs with an additional membrane that is disrupted prior to fusion of the MV with the cell during entry. The first step in virus replication is entry. The mechanisms used by poxviruses are complicated by the existence of two distinct infectious forms with different external membranes. Another complicating factor is the ability of vaccinia virus to enter cells through the plasma membrane and by endocytosis. We have identified a complex comprised of at least 11 proteins that are conserved in all poxviruses and required for entry of both infectious forms of virus. These proteins are conserved in all members of the poxvirus family, suggesting a common entry mechanism. Previous studies have all analyzed the entry-fusion complex following denaturation to separate the component polypeptides. New experiments are designed to isolate the intact complex in order to carry out structural studies.