Particle Morphogenesis

Principles and Mechanism of The Retroviral Particle Morphogenesis

The orthoretroviral Gag (group specific antigen) polyprotein contains all structural information required for capsid assembly and particle release. Therefore expression of the orthoretroviral Gag protein by itself is sufficient for release of non-infectious, so-called virus-like-particles (VLPs). In context of replication competent, infectious virus particles the orthoretroviral Gag polyprotein forms the lipid-enveloped retroviral capsid. The Gag polyprotein is subsequently proteolytically processed by the viral encoded protease (PR) into matrix (MA), capsid (CA) and nucleocapsid (NC) subunits either during or shortly after particle release. Due to their capsid assembly process two major types of retroviruses can be distinguished. C-type retroviruses assembly their capsid completely at cellular membranes whereas B/D-type retroviruses preassembly their capsid completely in the cytoplasm of infected cells prior to transport and association to cellular membranes. In recent years different functional domains of the retroviral Gag protein were identified that are responsible for membrane association (M-domains), involved in Gag-Gag protein interactions (I-domains), or essential for interaction with cellular proteins during late phases of the particle release or budding process (L-domains). 
The research of our lab concentrates on a special type of retrovirus, the foamy- or spumaretroviruses. Foamy viruses (FV) constitute the only genus of the retroviral subfamily Spumaretrovirinae within the family of retroviruses (Retroviridae). The FV replication strategy shows many unique features compared to all other retroviruses. Interestingly some of these unique features of the FV replication cycle bear strong homology to features of the replication strategy of Hepatitis B virus (HBV). 
The FV Gag polyprotein and the FV particle morphogenesis display several unique features not observed for orthoretroviruses. The FV Gag polyprotein for example is not processed like orthoretroviral Gag proteins into MA, CA, and NC subunits. In respect to their capsid assembly strategy FV resemble B/D-type retroviruses and preassemble their capsid in the cytoplasm before membrane association can occur. However, unlike as reported for other retroviruses the membrane association of FV capsids is only observed upon coexpression of the cognate viral glycoprotein, pointing to a very specific interaction between both proteins during the budding process. 

In respect to the mechanistic analysis of retroviral particle assembly and egress we are interested in, 

• the characterization of domains in different viral structural proteins that are essential for these processes;  
• the analysis of interaction of various viral structural proteins with themselves and with each other during these steps of the FV replication cycle;  
• the identification of cellular interaction partners and cellular pathways exploited by FV for particle release;  
• the unraveling of the mechanism underlying the regulation of the balance between viral- and subviral particle release of FVs.