Bio Ch. 19

General features of viral replicative cycles

- A virus is an intracellular parasite that uses the equipment and small molecules of its host cell to replicate. A viral infection begins when a virus binds to a host cell and the viral genome makes its way inside. Different viruses and different host cells have different methods of genome entry. Some viruses are taken in by endocytosis by fusion of the viral envelope with the host's plasma membrane. Once the genome is inside, the proteins it encodes can take over the host cell, reprogramming it to copy the viral genome and manufacture viral proteins. The host provides the nucleotides for making viral nucleic acids, as well as enzymes, ribosomes, tRNAs, amino acids, ATP, and more. Many DNA viruses use the cell's DNA polymerases to synthesize new genomes along the viral DNA's templates. RNA viruses use virally encoded RNA polymerases that can use RNA as a template (uninfected cells generally don't make enzymes for carrying out this process). After being produced, the viral nucleic acid and capsomeres spontaneously self-assemble into new viruses. The simplest type of viral replicative cycle ends with the exit of hundreds or thousands of viruses from the infected hot cell, a process that often damages or destroys the cell. The viral progeny that exit the cell have the potential to infect additional cells. (1) The virus enters the cell and is uncoated, releasing viral DNA and capsid proteins. (2) Host enzymes replicate the viral genome. (3) At the same time, host enzymes transcribe the viral genome into viral mRNA, which host ribosomes use to make more capsid proteins. (4) Viral genomes and capsid proteins self-assemble into new virus particles, which exit the cell.

Capsids and envelopes

- Capsid: the protein shell enclosing the viral genome; can be rod-shaped, polyhedral, or a more complex shape; built from a large number of protein subunits called capsomeres, but the number of different kinds of proteins in a capsid is usually small. - Rod-shaped viruses are commonly called helical viruses because they're made from a single type of protein arranged in a helix. Tobacco mosaic virus is an example. - Icosahedral viruses have identical protein molecules arranged in a polyhedral capsid with triangle faces. Adenoviruses are an example. - Viral envelopes: a membranous envelope that surrounds the capsid of viruses; an accessory structure that helps the virus infect its host; derived from the membranes of the host cell; contain phospholipids and membrane proteins as well as glycoproteins and proteins of viral origin. Some viruses carry a few viral enzyme molecules within their capsids. Influenza is an example. - Bacteriophages (or phages): have complex capsids; infect bacteria; have an icosahedral head that encloses their DNA and a tail apparatus made of proteins with fibers that attach to a bacterial cell.

Viral diseases in plants

- Common signs of viral infection in plants: bleached or brown spots on leaves and fruits, stunted growth, and damaged flowers or roots. - Plant viruses have the same basic structure and mode of replication as animal viruses and most have an RNA genome and a helical capsid or an icosahedral capsid. - Viral diseases of plants are spread by 2 major routes: horizontal transmission and vertical transmission. Horizontal transmission: plant is infected from an external source of the virus; more susceptible if the skin has been damaged by wind, injury, or herbivores, which allow the pathogen in; insects and other organisms can act as disease carriers. Vertical transmission: plant inherits a viral infection form a parent; can occur in sexual propagation (e.g. cutting) or in sexual reproduction. - Viral genomes and associated proteins can spread throughout a plant by plasmodesmata. The passage of viral macromolecules from cell to cell is facilitated by virally encoded proteins that cause enlargement of plasmodesmata.

Emerging viruses

- Emerging viruses: viruses that suddenly become apparent, e.g. HIV, ebola. - Epidemic: a widespread outbreak, e.g. influenza. Pandemic: a global epidemic, e.g. H1N1. - 3 processes contribute to the emergence of viral diseases: (1) Mutation of existing viruses; perhaps the most important; RNA viruses have high rates of mutation because viral RNA polymerases don't proofread and correct errors in replicating their RNA genomes; some mutations change viruses into new genetic varieties (strains); e.g. seasonal flu epidemics. (2) Dissemination of a viral disease from a small, isolated human population; often spread by social and technological travels; e.g. AIDS. (3) The spread of existing viruses from other animals, e.g. H1N1 spread from pigs. - Viruses that can infect humans and animals are generally far more deadly than those that can just infect humans, e.g. the Spanish flu. The virus may mutate as it passes from one species to another; the different strains can undergo genetic recombination if the RNA molecules making up the genomes mix and match during viral assembly; coupled with mutation these reassortments can lead to the emergence of a viral strain capable of infecting human cells. A great host range increases the chances for reassortment between different strains. - Emerging viruses are generally not new; they're existing viruses that mutate, disseminate more widely in the current host species, or spread to new host species. Changes in host behavior or environmental changes can increase the viral traffic responsible for emerging disease.

The lysogenic cycle

- Lysogenic cycle: allows replication of the phage genome without killing or destroying the host cell (like the lytic cycle does). Phages capable of using the lytic and lysogenic cycles are called temperate phages. - For example, a lambda phage binds to the surface of a cell and injects its linear DNA genome. Within the host, the lambda DNA forms a circle; the next step is dependent on whether the phage replicates by the lytic or lysogenic cycle. During a lytic cycle, the viral genes immediately turn the host cell into a lambda-producing factory, and the cell soon lyses and releases more viruses. During a lysogenic cycle, the lambda DNA molecule is incorporated in a specific site on the host cell chromosome by viral proteins that break both circular DNA molecules to join them together. When integrated into the host cell chromosome this way, the viral DNA is called a prophage. One prophage gene codes for a protein that prevents transcription of most other prophage genes; thus, the phage genome is mostly silent within the host cell. Every time the host cell prepares to divide, it replicates the prophage, and each daughter cell inherits it. This mechanism allows viruses to propagate without killing the host cells they depend on. - An environmental signal, such as a certain chemical or high-energy radiation, usually triggers the switchover form the lysogenic to lytic cycle. A few other genes may be expressed during lysogeny, and the expression of these genes may later be seen in the host's phenotype. - After entering the bacterial cell and circularizing, the DNA can immediately initiate the production of a large number of progeny phages (lytic cycle) or integrate into the bacterial chromosome (lysogenic cycle). In most cases, the phage follows the lytic pathway; however, once a lysogenic cycle begins, the prophage may be carried in the host cell's chromosome for many generations. The phage has one main tail fiber, which is short. - Lysogenic cycle: phage DNA integrates into the bacterial chromosome, becoming a prophage -> the bacterium reproduces normally, copying the prophage and transmitting it to daughter cells -> many cell divisions produce a large population of bacteria infected with the prophage OR a prophage exits the bacterial chromosome, initiating a lytic cycle; happens occasionally - Lytic cycle: lytic cycle is induced -> new phage DNA and proteins are synthesized and self-assemble into phages -> the cell lyses, releasing phages -> the phage attaches to a host cell and injects its DNA -> phage DNA circularizes -> cycle begins again

The lytic cycle

- Some double-stranded DNA can replicate by 2 alternative mechanisms: the lytic cycle and the lysogenic cycle. - Lytic cycle: a phage replicative cycle that culminates in the death of the host cell; refers to the last stage of infection, during which the bacterium lyses (breaks open) and releases the phages that were made within the cell, which can injure a healthy cell. A few successive lytic cycles can destroy an entire bacterial population in just a few hours. - Virulent phage: a phage that replicates only by a lytic cycle. - Bacterial defenses against phages: natural selection favors bacterial mutants with surface proteins that aren't recognized as receptors by particular phages; DNA of a virus is often recognized as foreign when it enters a bacteria and is cut up by cellular enzymes called restriction enzymes; the bacteria cell's own DNA is methylated to prevent attack by its own restriction enzymes. However, natural selection also favors phages that can bid to the altered bacteria receptors or are resistant to restriction enzymes. (1) Attachment: The T4 phage uses its tail fibers to bind to specific surface proteins on a cell that act as receptors. (2) Entry of phage DNA and degradation of host DNA. The sheath of the tail contracts, injecting the phage DNA into the cell and leaving an empty capsid outside. The cell's DNA is hydrolyzed. (3) Synthesis of viral genomes and proteins. The phage DNA directs production of phage proteins and copies of the phage genome by host and viral enzymes, using components within the cell. (4) Self-assembly. 3 separate sets of proteins self-assemble to form phage heads, tails, and tail fibers. The phage genome is packaged side the capsid as the head forms. (5) Release. The phage directs production of an enzyme that damages the bacterial cell wall, allowing fluid to center. The cell swells and eventually bursts, releasing phage particles. - The phage DNA is protected from breakdown because it contains a modified form of cytosine that isn't recognized by the phage enzyme. - The entire lytic cycle takes about 20-30 minutes to complete in a 37 degree environment.

Viral envelopes

- The envelope is an outer membrane that a virus uses to enter a host cell. The envelope has glycoproteins protruding from its outer surface that bind to specific receptor molecules on the surface of a host cell. Ribosomes bound to the ER of the host cell make the protein parts of the envelope glycoproteins; cellular enzymes in the ER and Golgi the add the sugars. New viral capsids are wrapped in membrane as they bud from the cell. As you can see, the viral envelope is derived from the host cells plasma membrane, although all or most of the molecules of this membrane are specified by the viral genes. - Some viruses have envelopes that aren't derived from the plasma membrane; some are temporarily cloaked in membrane derived form the host's nuclear envelope, which the virus then sheds and acquires a new envelope form the Golgi; these viruses have double-stranded DNA genome and replicate within the host cell nucleus using a combination of viral and cellular enzymes to replicate and transcribe their DNA. Copies of the viral DNA can remain behind as mini-chromosomes in the nuclei of certain nerve cells, remaining latent until some physical or emotional stress triggers a new round of active virus production. Replicative cycle of an enveloped RNA virus: (1) Glycoproteins on the viral envelope bind to specific receptor molecules on the host cell, promoting viral uptake by the cell. (2) The capsid and viral genome enter the cell. Digestion of the capsid by cellular enzymes releases the viral genome. (3) The viral genome functions as a template for synthesis of complementary RNA strands by a viral RNA polymerase. (4) New copies of viral genome RNA are made using the complementary RNA strands as templates. (5) Complementary RNA strands also function as mRNA, which is translated into both capsid proteins (in the cytosol) and glycoproteins for the viral envelope (in the ER and Golgi). (6) Vesicles transport envelope glycoproteins to the plasma membrane. (7) A capsid assembles around each viral genome molecule. (8) Each new virus buds from the cell, its envelope studded with viral glycoproteins embedded in membrane derived from the host cell.

Viral genomes

- The genomes of viruses may consist of double-stranded DNA, single-stranded DNA, double-stranded RNA, or single-stranded RNA, depending on the type of virus. A virus is called a DNA or RNA virus based on the kind of nucleic acid that makes up its genome. - A virus's genome is usually organized as a single linear or circular molecule of nucleic acid, although some viruses have genomes consisting of multiple molecules of nucleic acid. The smallest viruses only have 3 genes, while the largest have several hundred to a thousand.

Structure of viruses

- The tiniest viruses are even smaller than a ribosome; millions could easily fit in a pinhead. Even the largest known virus is barely visible under a light microscope. Some viruses can be crystallized; not even the simplest of cells can aggregate into regular crystals. - Virus: an infectious particle consisting of nucleic acid enclosed in a protein coat and, for some viruses, surrounded by a membranous envelope.

Replicative cycles of animal viruses

- The viral genome (double- or single-stranded DNA or RNA) is the basis for the common classification of viruses. Single-stranded RNA viruses are further classified according to how the RNA genome functions in a host cell. - Few bacteriophages have an envelope or RNA genome, but many animal viruses have both, in fact nearly all do, as do some with DNA genomes.

RNA as viral genetic material

- There are 3 types of single-stranded RNA genomes found in animal viruses: Class IV viruses can directly serve as mRNA and be translated int viral protein immediately after infection; Class V viruses have an RNA genome that serves as a template for mRNA synthesis; Class VI viruses (retroviruses) are equipped with the enzyme reverse transcriptase, which transcribes an RNA template into DNA, providing an RNA to DNA flow, the opposite of the usual direction, and retroviruses contain 2 identical molecules of single-stranded RNA and 2 molecules of reverse transcriptase, e.g. HIV - All viruses that use an RNA genome as a template for mRNA transcription require RNA -> RNA synthesis. These viruses use a viral enzyme capable of carrying out this process; there are no enzymes in most cell. This enzyme is packaged with the genome inside the viral capsid. - After a retrovirus enters a host cell, its reverse transcriptase molecules are released into the cytoplasm and catalyze the synthesis of viral DNA. the newly made viral DNA enters the cell's nucleus and integrates into the DNA of a chromosome. The integrated viral DNA, called a provirus, never leaves the host's genome and becomes a permanent resident of a cell (a prophage, conversely, leaves the host's genome at the start of the lytic cycle). The RNA polymerase of the host transcribes the proviral DNA into RNA molecules, which can act both as mRNA for the synthesis of viral protein and as genomes for the new viruses that'll be assembled and released form the cell. HIV replicative cycle: (1) The envelope glycoproteins allow the virus to bind to specific receptors on certain white blood cells. (2) The virus fuses with the cell's plasma membrane. The capsid protein are removed, relaxing the viral proteins and RNA. (3) Reverse transcriptase catalyzes the synthesis of a DNA strand complementary to the viral RNA. (4) Reverse transcriptase catalyzes the synthesis of a second DNA strand complementary to the first. (5) The double-starnded DNA is incorporated as a provirus into the cell's DNA. (6) Proviral genes are transcribed into RNA molecules, which serve as genomes for offspring viruses and as mRNAs for translation into viral protein. (7) The viral proteins include capsid protein and reverse transcriptase (made in the cytosol) and envelope glycoproteins (made in the ER). (8) Vesicles transport the glycoproteins to the cell's plasma membrane. (9) Capsids are assembled around viral genomes and reverse transcriptase molecules. (10) New viruses, with viral envelope glycoproteins, bud from the host cell.

Viroids and prions: the simplest infectious agents

- Viroids: circular RNA molecules, only a few hundred nucleotides long, and infect plants; don't encode proteins but can replicate in the host plant cells using host cell enzymes; cause errors in the regulatory systems that control plant growth; signs influence abnormal development and stunted growth. Nucleic acids that show how single molecules can be an infectious agent that spreads a disease. - Prions: proteins that cause a number of degenerative brain diseases in various animals; can be transmitted in food; act very slowly, with an incubation period of at least 10 years before symptoms develop that prevents infection sources from being identified until long after the first cases appear; virtually indestructible, and not destroyed or deactivated by heating; have no known cure. Prions are misfolded forms of normal brain proteins that somehow convert other normal protein molecules to the misfolded prion versions. Several prions then aggregate into a complex that can convert other normal proteins to prions, which join the chain. Prion aggregation interferes with normal cellular functions and causes disease symptoms, cellular malfunction, and the eventual degeneration of the brain.

Evolution of viruses

- Viruses can't replicate their genes or generate its own ATP, but they do have a genetic program written in the universal language of life. - Viruses infect every form of life. They likely evolved after the first cells appeared since they depend on cells for their own propagation. - Some biologists think viruses originated from naked bits of cellular nucleic acids that moved from one cell to another; the evolution of capsid proteins may have allowed viruses to bind cell membranes, thus facilitating the infection of uninjured cells. - Plasmids: small, circular DNA molecules found in bacteria and yeasts; exist apart from and can replicate independently of the bacterial chromosome and are occasionally transferred between cells. Transposons: DNA segments that can move from one location to another within a cell's genome. Plasmids, transposons, and viruses are all mobile genetic elements. - A viral genome can have more in common with the host genome it infects than with other viruses. Some viral genes are identical to their host cell's genes. However, the genetic sequences of some viruses are similar to those of seemingly distantly related viruses, e.g. plant and animal viruses; this may reflect the viral genes favored by natural selection during early viral development.

Viruses replicate only in host cells

- Viruses lack metabolic enzymes and equipment for making proteins; they're obligate intracellular parasites, meaning they can only replicate within a host cell. Each particular virus can infect cells of only a limited number of host species, called the host range of the virus. This host specificity results from the evolution of recognition systems by the virus. Viruses usually identify host cells by a "lock-and-key" fit between viral surface protein and specific receptor molecules on the outside of cells. The receptor molecules originally carried out functions that benefited the host cell but were co-opted by viruses as portals of entry. Some viruses have broad host ranges, e.g. West Nile virus. Other viruses have host ranges so narrow they can only infect one species, e.g. measles. Viral infection of multicellular eukaryotes is usually limited to particular tissues, e.g. AIDS and the immune system.

Viral disease in animals

- Viruses may damage or kill cells by causing the release of hydrolytic enzymes from lysosomes. Some viruses cause infected cells to make toxins, and some have molecular components that are toxic (e.g. envelope proteins). How much damage a virus causes partly depends on how well the infected tissue can regenerate by cell division. - Vaccine: a harmless variant or derivative of a pathogen that stimulates the immune system to mount defenses against the pathogen. - Medical technology at present can do very little to cure most viral infections once they occur. Most antiviral drugs resemble nucleosides, so they interfere with viral nucleic acid synthesis.

The discovery of viruses

- Viruses were discovered via tobacco mosaic disease. Martinus Beijernick is often credited with being the first scientist to voice the concept of a virus.