Virion assembly

The shell of all picomaviruses is built up from 60 copies each of four polypeptide chains, called VPl to VP4. These are translated from the viral RNA into a single polypeptide, which is posttranslationally processed by stepwise proteolysis involving viraily encoded enzymes. First, the polypeptide chain is cleaved into three proteins VPO (which is the precursor for VP2 and VP4), VPl and VP3. These proteins begin the assembly process. The last step of the processing cascade occurs during completion of the virion assembly the precursor protein VPO is cleaved into VP2 and VP4 by a mechanism that is probably autocatalytic but may also involve the viral RNA. VPl, VP2, and VP3 have molecular masses of around 30,000 daltons, whereas VP4 is small, being 7000 daltons, and is completely buried inside the virion. 

Fig. 1 Antiviral genes inhibit virus replication at different stages of the viral life cycle. Early inhibitors prevent the establishment of the viral genome in the target cell (class I, e.g., entry inhibitors, RT inhibitors for HIV). Intermediate inhibitors prevent viral gene expression or amplification of the viral genome (class II, e.g., siRNAs, antisense RNAs). Late inhibitors prevent virion assembly or release, or inactivate the mature virions (class III, e.g., transdominant core proteins, capsid-targeted virion inactivation, CTVI). A list of antiviral genes in each class is found in Table 1...

Schmitz, 1., and Rao, A. L. N. (1998). Deletions in the conserved amino-terminal basic arm of cucumber mosaic virus coat protein disrupt virion assembly but-do not abolish infectivity and cell-to-cell movement. Virology 248, 323-331. 

Retroviruses encode a protease (PR) responsible for cleaving polyprotein precursors, and such processing is essential for proper virion assembly and maturation. Based on the presence of a sequence Asp-Ser/Thr-Gly in the active sites of retroviral proteases (1) and their inhibition in vitro by pepstatin (2-7), these enzymes have been classified as members of the aspartic protease family. Crystal structures have been determined for the proteases from Rous sarcoma virus (RSV PR) (8), from two variants and several mutants of the human immunodeficiency vims (HIV PR) (9-11), from feline immunodeficiency virus (FIV PR) (12) and from equine infectious anemia vims (EIAV PR) (13). Aspartic proteases contain a single active site which includes two aspartates. In apoenzymes, the two catalytic Asp residues from the active site triad have been found to be in hydrogen bond contact with a water molecule (10). Mutations of the active site Asp25 in HIV-1 PR into Asn (14,15), Thr (3) or Ala (4,16,17) led to an inactive enzyme. Similarly, the RSV PR was inactivated by mutation of its active site Asp to He (18). 

In more complex viruses, the nucleocapsid is surrounded by a membrane envelope, which usually arises from the host cell nuclear or plasma membranes. Envelope proteins, coded for by the viral genome, are inserted into the envelope membrane during virion assembly. Proteins that protrude from the surface of the envelope, called spikes, are believed to mediate the attachment of the virus to the host cell. Representative viruses are illustrated in Figure 17.24. 

Craven, R.C., Bennett, R.P. Wills, J.W. (1991). Role of the avian retroviral protease in the activation of reverse transcriptase during virion assembly. ]. Virol, 65, 6205-17. 

Erickson KD, Bouchet-Marquis C, Heiser K, Szomolanyi-Tsuda E, Mishra R, Ljunothe B, Hoenger A, Garcea RL. Virion assembly factories in the nucleus of polyoma-infected cells. PLoS Pathog. 2012 8(4) el002630. 

Fig. 1. Time course of synthesis of viral DNA, RNA, and proteins and virion assembly in Ad2-infected cells. The measurements of intracellular virus and viral DNA (pfu/cell) are from Green et al. (1971), and those of viral mRNA, measured by hybridization of [ H]-RNA to Ad2 DNA, and late protein, and hexon antigen measured by complement fixation from Philipson and Lindberg (1974). Modified from Tooze (1980).

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