Synthesis, Assembly, and Processing of Viral Proteins

Excerpt

Transfer of the RNA genome of a retrovirus from one cell to another requires its assembly within the structure of an infectious virion. Although most of the components of the retroviral particle have been identified (see Fig. 1 and Chapter 2), the molecular details of the assembly mechanisms are poorly understood. This may seem surprising since the number of distinct proteins contained in a retrovirus is small. What makes the process of assembly both difficult and interesting to study is its highly dynamic nature.

An examination of the mature retroviral particle cannot fully explain the steps in assembly because these components are not those from which the particle was made. Rather, all of the structural proteins of the virion, with few exceptions, are derived from three polyproteins: Gag, Gag-Pro-Pol, and Env (Fig. 2). Each of these precursor proteins has special characteristics needed for specific steps in the assembly process, and each undergoes extensive changes along the way. In brief, the surface (SU) and transmembrane (TM) proteins found on the surface of the virion are initially synthesized as a single polypeptide, the Env glycoprotein, which is assembled into oligomeric complexes in the rough endoplasmic reticulum (RER), extensively modified, and then cleaved by a cell-encoded protease during transport to the surface of the cell. In some instances, further proteolytic processing of TM occurs after the particle is released. Likewise, the proteins found on the inside the virion (matrix, MA; capsid, CA; nucleocapsid, NC; protease, PR; reverse transcriptase, RT; integrase, IN) are initially linked within the Gag and Gag-Pro-Pol proteins. The Gag protein is sufficient for directing budding at the plasma membrane, and the Pro-Pol polyproteins are incorporated into the resulting particle because they are linked to Gag. Subsequent cleavage of the Gag and Gag-Pro-Pol proteins by the viral protease brings about new shapes and arrangements inside the nascent virion as the immature particle undergoes a metamorphosis into the mature, infectious retrovirus. Even the structure of the viral RNA, packaged into the virion through an interaction with Gag, changes during the budding and maturation process.