Discovery of Viruses

Viral Structure

Replication of Viruses

Bacterial Viruses

Plant Viruses & Viroids

Animal Viruses

Origin of Viruses

Bacterium and Its Genome

Transfer & Recombination of Bacterial Genes

Control of Gene Expression in Prokaryotes

• The molecular mechanisms of heredity were first elucidated in viruses and bacteria, the simplest biological systems.  Most, but not all, of the molecular principles are applicable to higher organisms.
• The unique aspects of microbial genetics made possible a greater understanding of many diseases and the emergence of biotechnology.

• In the nineteenth century, viruses were known only as mysterious agents causing tobacco mosaic disease.  These invisible pathogens were found to be extremely small, capable of reproducing within host cells but not on nutrient media, and, unlike bacteria, resistant to destruction by alcohol.
• It was not until the twentieth century that viruses were finally crystallized and observed under the electron microscope.

• Viruses are not cells, but in their simplest form consist only of nucleic acid enclosed in a protein shell.
• The viral genome may be double- or single-stranded DNA, or single- or double-stranded RNA, depending on the specific virus.
• The protein shell enclosing the genome is a variously shaped capsid built from many protein subunits.  Some animal viruses have a membranous envelope outside the capsid made of both host and viral material.  Some bacterial viruses, also called bacteriophages or phages, have the most complex capsids, consisting of complex heads with protein tailpieces.

The Replication of Viruses

• Viruses are obligate intracellular parasites whose genome uses the enzymes, ribosomes, and small molecules of host cells to synthesize multiple copies of itself and the viral capsid.  These constituents self-assemble into virions that leave the cell, ready to infect a new host.
• Viruses replicate their genome by one of three routes, often using enzymes encoded by their nucleic acid.  DNA viruses replicate their DNA much as a cell does.  RNA viruses either make complementary RNA strands directly with RNA replicase or use reverse transcriptase to catalyze formation of complementary DNA; the DNA is then transcribed into the viral genome and messenger RNA.
• The packaging of viral genomes inside capsids is generally a nonenzymatic, spontaneous process resulting from noncovalent interactions between chemical groups within the molecules.
• Each type of Virus has a characteristic home range, determined by specific receptor sites on the surface of host cells.

Bacterial Viruses

• Bacteriophages have been an important source of knowledge about the nature of DNA and nucleic acid replication.
• In the lytic cycle of phage replication, injection of a virulent bacteriophage genome into a bacterium programs destruction of host DNA, production of new virions, and lysozyme to digest the bacterial cell wall, which bursts and releases the new virus particles.
• Bacteria resist viral subversion by producing restriction enzymes that cut up foreign DNA.  A continuous coevolution between viruses and their hosts allows perpetuation of the lytic cycle without concomitant destruction of all bacteria.
• Temperate bacteriophages coexist with their hosts in the lysogenic state by inserting their genome into the bacterial chromosome as a prophage, which codes for a repressor protein that keeps most of its genes inactive.  In this innocuous form, the virus can be passed on indefinitely to host daughter dells until at some point it is stimulated to leave the bacterial chromosome and initiate a lytic cycle or a lysogenic cycle in new host cells.
• Expression of a few prophage genes in a lysogenic cell can change the phenotype of the bacterium in a process called lysogenic conversion, which may render an otherwise harmless bacterium pathogenic.

Plant Viruses and Viroids

• Most plant viruses are RNA viruses that seriously compromise plant growth and development.
• Plant viral diseases may be spread by horizontal transmission, from an external source through a damaged epidermis or via insect vectors; or they may be spread by vertical transmission, the inheritance of viral infections.
• Plant diseases can also by caused by viroids, tiny molecules of naked RNA that are believed to interfere with plant growth and development by disrupting genetic regulatory systems.

Animal Viruses

• Animal viruses are often shrouded in an envelope acquired from host cell membrane.  Such an envelope allows easy entry and exit through plasma membrane of host cells.
• Some viruses, such as the herpesviruses, may integrate into the host chromosome as a latent provirus.
• Viral infections in animals create a spectrum of effects, depending on the precise mechanism of viral damage and the ability of the infected tissue to regenerate.
• Vaccines against specific viruses stimulate the immune system to defend the host against an infection.  Newly developed antiviral drugs offer promise of halting viral replication once infection has occurred.
• Viruses have long been implicated in causing cancer, and the study of retroviruses has been especially important in cancer research.  Tumor viruses permanently insert viral DNA into host cell DNA, triggering subsequent cancerous changes through their own or host cell oncogenes.  Oncogenes code for cellular growth factors or proteins involved in growth factor action.

The Origin of Viruses

• Although there is debate about whether or not viruses are alive, there is agreement that they evolve.
• Various lines of evidence point to the origin of viruses as fragments of cellular nucleic acid that came to acquire specialized packaging.

The Bacterium and Its Genome

• The bacterial chromosome is a circular, relatively simple structure with few associated proteins.  Accessory genes are carried on smaller rings of DNA called plasmids.
• Chromosomal replication in bacteria proceeds bidirectionally from a single origin of replication.

Transfer and Recombination of bacterial genes

• Bacteria have three mechanisms of transferring genes between cells.
• In the first mechanism, called transformation, naked DNA enters the cell from the surroundings and becomes incorporated into the chromosome by recombination.
• A second mechanism is general or restricted transduction, in which bacterial DNA is carried from one cell to another by bacteriophages.
•  A third mechanism is conjugation, a primitive kind of mating in which F⁺  or Hfr cell transfers DNA to an F^- cell.  The transfer is brought about by a plasmid called the F (fertility) factor, which carries genes for the sex pili and other functions needed for mating.  In an Hfr cell, the F factor is integrated into the bacterial chromosome, and the Hfr cell will transfer chromosomal DNA along with the F-factor DNA in conjugation.
• Matings between the Hfr cells and F^- cells yield partially diploid cells and then recombinant bacteria as a result of crossing over between the newly acquired DNA and the recipient's DNA.
• Since genes are always transferred in the same sequence during the Hfr conjugation, the bacterial chromosome can be mapped by disrupting the process after various durations. Frequencies of recombination are used to refine the map.
• Episomes are plasmids, such as the F factor, that can integrate into the bacterial chromosomes.
• R plasmids confer resistance to various antibiotics on a bacterium.  Their transfer to pathogenic cells poses serious medical problems.
• Transposons, or "jumping genes," first identified in maize, have been found in many organisms.  They generally have at least a transposase gene for cutting and ligating DNA and inverted repeat sequences at each end of the transposon that serve as recognition sites for the transposase.
• Insertion sequences, the simplest transposons, may affect gene function as they move about.
• Complex transposons, such as the F factor, R plasmids, and the DNA versions of retrovirus genomes, include additional genetic material not connected with transposition.

The Control of Gene Expression in Prokaryotes

• Cells control metabolism by regulating enzyme activity or by regulating enzyme synthesis through activation or inactivation of selected genes.
• Some genes, the constitutive genes, are unregulated, continuously transcribed and translated into proteins that are always needed by the cell.  "Weak" and "strong" promotor regions cause transcription of different genes to initiate with different frequencies.
• In bacteria, regulated genes are often clustered into units called operons, consisting of a single promotor serving adjacent structural genes.  A region called the operator, overlapping the promoter, serves as the on/off switch controlling the operon.  Binding of a specific repressor protein to the operator  shuts off transcription by blocking attachment of RNA polymerase, whereas binding of an activator protein stimulates transcription.
• Regulatory genes, which code for repressor and activator proteins, are usually constitutive and may be located at some distance from the operon.
• A repressible operon is switched off in the presence of a key metabolite, usually an end product of a biochemical pathway; the metabolite acts as a corepressor by binding to the normally inactive repressor protein and enhancing its ability to bind to the operator.  This action prevents wasteful overproduction of enzymes.
• Inducible operons are quiescent until activated by a key metabolite.  In contrast with the repressible system, binding of the metabolite to the innately active repressor prevents its attachment to the operator, thereby turning on structural genes when necessary.
• Both repressible and inducible operons are examples of negative control, although the mechanisms and types of metabolic pathways controlled are different.
• Inducible operons can also involve positive control via a stimulatory activator protein.  For example, catabolite activator protein (CAP) stimulates transcription by binding to the promoter and enhancing its ability to associate with RNA polymerase.  The promoter-binding ability of CAP is in turn dependent on the presence of cyclic AMP, which accumulates when glucose is scarce.
• CAP works with repressors to optimize the function of several different operons involved in catabolic backup systems, thereby conferring versatility and economy on the cell.