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

Viruses
Non-lytic viral life cycle

7.4.1. Lysogeny. Some bacterial Viruses, known as non-lytic (temperate) phages, associate with the host Cell in a non-lytic manner and therefore do not cause cell death. For example, upon infection of E. coli by bacteriophage λ, the viral DNA may integrate into the host chromosome instead of replicating.

Such a chromosome-integrated viral DNA is called a prophage (or provirus), and The phenomenon of incorporating the viral DNA into the host cell's chromosome is known as lysogeny.

Bacteriophages capable of integrating into bacterial Chromosomes are called lysogenic bacteriophages.

Under certain conditions (for instance, sometimes upon ultraviolet irradiation), the prophage DNA of a lysogenic bacterium is activated, excised from the chromosome, and triggers the lytic cycle, leading to the synthesis and release of progeny virions.

7.4.2. Retroviruses. The genomes of many animal viruses can also integrate into the chromosomes of infected Cells. The most interesting among them are retroviruses—enveloped viruses with a genome consisting of two identical RNA strands.

The very name retroviruses reflects the fact that a part of their life cycle involves a process reverse to normal METABOLISM/31.html">Transcription, i.e., the Transcription of DNA into RNA. Their RNA genome serves as a template from which a DNA molecule is synthesized by a special enzyme, Reverse Transcriptase.

Reverse transcriptase in the retrovirus life cycle (Figure 72) first copies the viral RNA into complementary single-stranded DNA, and then, using this first strand, synthesizes a second, complementary DNA strand.

At The First stage of the retrovirus life cycle, after envelope Glycoproteins attach to The Cell membrane, the retrovirus envelope fuses with the host Plasma Membrane, and the nucleocapsid enters the Cytoplasm (Figure 72, step 1).

Next, the retrovirus reverse transcriptase, along with other Proteins, copies the viral single-stranded RNA (ssRNA) into double-stranded DNA (dsDNA) (Figure 72, step 2).

The viral dsDNA is transported into the Cell Nucleus and integrates into one of many possible sites within the infected cell's chromosomal DNA, forming a so-called provirus (Figure 72, step 3). For simplicity, Figure 72 shows only a single cell chromosome.

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Figure 72 - Life Cycle of a retrovirus

Thus, viral infection results in a permanent genetic alteration within the infected cell.

Further, the integrated viral DNA (provirus) is transcribed by cellular RNA polymerase to produce genomic RNAs and Messenger RNA (mRNA), from which the cellular translational machinery synthesizes viral glycoproteins and nucleocapsid proteins (Figure 72, step 4). This is followed by the assembly of progeny virions and their budding from the infected cell (Figure 72, step 5).

Since most retroviruses do not kill their host cells, these cells can continue to replicate, giving rise to daughter cells with the initially integrated prophage DNA. These daughter cells continue to transcribe the prophage DNA and bud off subsequent generations of virions.

Some retroviruses contain genes that cause Cancer, known as oncogenes, and infection of cells with such viruses leads to the transformation (malignant conversion) of infected cells into tumor cells. Studies of Oncogenic Viruses (primarily avian and murine viruses) have significantly advanced our understanding of the processes leading to the Transformation of a normal cell into a tumor cell.

Among known human retroviruses, we should note the human T-cell lymphotropic virus (HTLV), which causes certain forms of leukemia, and the HUMAN IMMUNODEFICIENCY VIRUS (HIV), which causes Acquired Immunodeficiency Syndrome (AIDS).

Both of these viruses can infect only specific cells, primarily certain cells of The Immune System and, in the case of HIV, certain Neurons of the Central Nervous system and glial cells. Only these cells possess surface receptors that interact with viral envelope proteins, which explains the cellular Specificity of these viruses.

Unlike most other retroviruses, HIV ultimately kills infected cells. The death of such a vast number of immune system cells leads to a breakdown of the body's Immune Response, i.e., AIDS.

Certain DNA viruses can also integrate into the chromosomes of infected cells. For example, the human papillomavirus (HPV) typically causes warts and other cutaneous growths. However, The Genome of certain HPV serotypes occasionally integrates into the chromosomal DNA of infected cervical epithelial cells, initiating The Development of Cervical cancer.

A serotype refers to the antigenic characteristics of Introduction/7.html">Cells and Viruses determined by serological Methods—a branch of immunology that studies interactions between Antigens and Antibodies in Blood serum.

Conclusions

Viruses are obligate parasites that can replicate only inside infected cells. Viral genomes can consist of either DNA (DNA viruses) or RNA (RNA viruses), and can be either single- or double-stranded.

The capsid surrounding the viral genome consists of multiple copies of one or a small number of different proteins encoded by the viral genome. Some viruses are surrounded by a lipoprotein envelope that resembles The Plasma Membrane but contains viral transmembrane proteins.

Most PLANT AND ANIMAL DNA viruses utilize the enzymatic machinery of infected cells to transcribe viral genomes into mRNA and synthesize progeny genomes. In contrast, most RNA viruses encode their own Enzymes that transcribe RNA genomes into viral mRNAs, from which new copies of RNA genomes are subsequently synthesized.

The translational machinery of infected cells—Ribosomes, tRNAs, and Translation factors—is utilized for the synthesis of all viral proteins.

A lytic viral infection, consisting of adsorption, penetration, synthesis of viral proteins and progeny genomes (Replication), assembly of progeny virions, and the release of hundreds or thousands of virions, leads to the death of the infected cell. The release of enveloped viruses occurs via budding from the host cell's plasma membrane.

A non-lytic infection occurs when the viral genome integrates into the DNA of the infected cell and typically does not lead to cell death.

Retroviruses are enveloped animal viruses possessing a single-stranded RNA genome. Upon entering the cell, the viral enzyme reverse transcriptase synthesizes a double-stranded DNA using the viral RNA as a template, which is then integrated into the host cell chromosome.

Unlike other retroviruses, HIV infection ultimately kills infected cells, causing severe Impairment of the body's immune response (AIDS).

Tumor viruses containing oncogenes may have either an RNA genome (e.g., human T-cell lymphotropic virus) or a DNA genome (e.g., human papillomavirus). In the case of such viruses, the Integration of the viral genome into the cellular chromosome triggers the transformation (malignant conversion) of the cell into a tumor cell.

Self-Assessment Questions

1. What is the difference between RNA viruses and DNA viruses?

2. WHAT IS A virion?

3. What is the host range of a virus?

4. Which viruses are known as bacteriophages?

5. What is a viral capsid?

6. What is a viral nucleocapsid?

7. What are the known TYPES OF VIRAL capsid Symmetry/Organization?

8. What components make up the lipoprotein envelope of viruses?

9. How does The Mechanism of interaction with cell receptors differ between small and large icosahedral viruses?

10. What is the plaque assay method for studying viruses?

11. List and characterize the MAIN STAGES OF the Lytic Pathway of viral development.

12. How does the assembly process differ between prokaryotic and eukaryotic DNA viruses?

13. How does the adsorption process differ between enveloped and non-enveloped viruses?

14. How do the cell release processes differ between enveloped and non-enveloped viruses?

15. What is lysogeny?

16. Which bacteriophages are referred to as lysogenic phages?

17. What viruses are called retroviruses?

18. What is the function of the enzyme reverse transcriptase?