Fundamentals of Molecular Biology. Part 2: Molecular Genetic Mechanisms - A. N. Ogurtsov 2011

Viruses
Lytic Pathway of Viral Growth

Despite the enormous diversity in the developmental details of specific Viruses, The life cycle of those that exhibit a lytic pathway follows these sequential stages.

7.3.1. Stages of the lytic cycle.

1. Adsorption – The virion attaches via its capsid Proteins to specific receptors On the surface of the host Cell.

2. Genome entry – The viral genome crosses The Plasma Membrane. In PLANT AND ANIMAL viruses, viral proteins are also introduced into the infected cell.

3. Replication – Viral mRNAs are synthesized using The Cell's genetic machinery—either METABOLISM/31.html">Transcription mechanisms in the case of DNA viruses, or, for RNA viruses, an enzymatic apparatus involving viral Enzymes. In both cases, viral mRNAs are translated by the cellular Translation machinery. Multiplication of the viral genome is directed either exclusively by viral proteins or with the participation of proteins from the infected cell.

4. Assembly – Viral proteins and replicated viral genomes associate to form progeny virions.

5. Release – The infected cell either undergoes rapid destruction (lysis), releasing all synthesized virions at once, or disintegrates gradually, releasing virions in the same progressive manner.

7.3.2. Prokaryotic DNA viruses. Figure 69 illustrates the lytic cycle of bacteriophage T4, a nonenveloped DNA virus that infects E. coli.

Once the proteins at the tip of the T4 "tail" bind to specific receptors on the cell surface, the viral genome is injected into the cell (Figure 69, stage 1).

Cellular enzymes transcribe the viral "early" genes, synthesizing mRNA from which "early" viral proteins are subsequently translated (Figure 69, stage 2).

Early proteins replicate the viral DNA and induce the expression of "late" viral proteins using the cell's enzymatic machinery (Figure 69, Stage 3).

Late viral proteins comprise the structural proteins for capsid assembly and enzymes that stimulate The breakdown of cellular DNA into NUCLEOTIDES, thereby supplying the necessary pool of "building blocks" for viral DNA Synthesis.

Progeny virions are assembled within the cell (Figure 69, stage 4) and released after viral proteins lyse and destroy the cell (Figure 69, stage 5). Viruses released following cell lysis initiate a new round of infection in other Cells of the Organism.

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Figure 69 - Lytic Life Cycle of E. coli bacteriophage T4

Viral capsid proteins are typically synthesized in large quantities, as numerous copies are required for the assembly of progeny virions. Each infected cell synthesizes and assembles approximately 100 to 200 progeny T4 virions, which are released upon cell lysis.

7.3.3. Eukaryotic DNA viruses. The lytic cycle is somewhat more complex in DNA viruses that infect Eukaryotic cells. In most such viruses, the viral DNA genome is transported (along with certain associated proteins) into the Cell Nucleus.

Inside The Nucleus, viral DNA is transcribed into RNA using the cell's transcription machinery. Processing of the viral pre-mRNA by cellular enzymes yields viral mRNA, which is transported to the Cytoplasm and translated into viral proteins by the Ribosomes, tRNAs, and translation factors of the infected cell.

Viral proteins are then transported back into the cell nucleus, where some either directly replicate the viral DNA or activate nuclear host proteins to drive Viral DNA replication, as occurs with the SV40 virus.

The assembly of capsid proteins with the newly synthesized viral DNA takes place within the cell nucleus, generating hundreds or even thousands of progeny virions.

7.3.4. Animal and plant RNA viruses. Conversely, most animal and plant RNA viruses do not rely on the genetic machinery of the cell nucleus for lytic propagation.

In some of these viruses, viral enzymes—introduced into the cell upon viral RNA entry—transcribe the viral RNA into mRNA directly within the Cell Cytoplasm.

This mRNA is translated into viral proteins by the cellular translation machinery. One or more of these proteins subsequently synthesize copies of the viral RNA.

Finally, progeny RNA genomes assemble with the synthesized capsid proteins to form progeny virions in the cytoplasm.

Once the synthesis of hundreds or thousands of new virions is complete, most infected Bacterial cells and certain infected plant and animal cells undergo lysis, releasing all virions simultaneously.

However, many plant and animal viral infections do not involve such a discrete lytic "event"; instead, the dying infected cell gradually releases virions as it progressively disintegrates.

7.3.5. Enveloped viruses. Many animal viruses possess a lipoprotein envelope derived from the host cell's plasma membrane, which contains A large number of viral Glycoproteins.

The processes of adsorption and release in enveloped viruses differ significantly from those in nonenveloped viruses.

As an example of lytic replication in an enveloped virus, let us examine the rabies virus (Figure 70).

Figure 70 - Lytic life cycle of the rabies virus

The rabies nucleocapsid consists of a single-stranded RNA genome surrounded by a protein capsid. Like other lytic RNA viruses, the rabies virion replicates in the cytoplasm and does not require the enzymatic machinery of the host cell nucleus. The rabies virus adsorbs via endocytosis, and progeny virions are released by budding from the plasma membrane of the infected cell.

The Structural components of the virus are listed at the top of the figure. Note that the nucleocapsid has a helical rather than an icosahedral shape.

Following adsorption of the virion to multiple copies of specific Membrane Proteins on the host cell (Figure 70, step 1), the virion is taken up by the cell via endocytosis to form an endosome (Figure 70, step 2).

Cellular proteins (proton pumps) in the endosomal membrane pump protons from the Cytosol into the endosome. The drop in endosomal pH induces a conformational change in the viral glycoproteins, which in turn leads to the fusion of the viral lipoprotein envelope with The Lipid Bilayer of the endosomal membrane, releasing the nucleocapsid into the cytosol (Figure 70, steps 3 and 4).

The viral RNA polymerase uses cytosolic ribonucleoside triphosphates (rNTPs) to replicate the viral RNA genome (Figure 70, step 5) and to synthesize viral mRNAs (Figure 70, step 6).

Transmembrane glycoproteins are translated from one of the viral mRNAs by ribosomes of The Endoplasmic reticulum (ER) and remain embedded in the ER membranes (Figure 70, step 7). Essential CARBOHYDRATES are added to them during maturation in the ER and the Golgi apparatus (Figure 70, step 8).

Vesicles containing the "matured" glycoproteins fuse with the plasma membrane of the infected cell, thereby positioning the receptor-binding domains of the glycoproteins on the outside of the cell (Figure 70, step 9).

Simultaneously, other viral mRNAs are translated on cellular ribosomes into nucleocapsid proteins, matrix proteins, and viral RNA polymerases (Figure 70, step 10).

All these proteins assemble with the viral genomic RNA replicated in step 5 to form a progeny nucleocapsid (Figure 70, step 11), which then attaches to the cytosolic domains of the viral transmembrane glycoproteins already embedded in the plasma membrane of the infected cell (Figure 70, step 12).

The plasma membrane wraps around the nucleocapsid to form a "bud," which pinches off (buds) to release the progeny virus outside the cell.

The budding of virions is clearly visible in Cytology/cytology/93.html">ELECTRON MICROGRAPHS OF infected cells, as shown in Figure 71.

Figure 71 - Progeny virions being released by budding from the plasma membrane of the infected cell

Tens of thousands of progeny virions bud from the infected cell before it eventually dies.