Viruses: Characteristics, Replication, and Classification
Viruses
Viruses are very small infective agents that consist of a core of nucleic acid and are dependent on a living host. They are viewed as nonliving particles by most biologists because they are not composed of cells and cannot carry on metabolic activities or reproduce on their own.
Virology
The study of viruses is called virology, and biologists who study viruses are virologists.
Replication
Viruses contain the nucleic acids necessary to make copies of themselves. They replicate by invading living cells and commandeering their metabolic machinery. Thus, viruses are obligate intracellular parasites.
Infection
Viruses infect all types of organisms, including bacteria, archaea, protists, plants, fungi, and animals. Some viruses even infect other viruses.
Evolution
Viruses evolve by natural selection. Most biologists view viruses as being at the edge of life, although a few argue that they are very simple life-forms.
Size
Most known viruses are very small, ranging in size from 20 to 300 nm. The paradigm that all viruses are very small and simple has been challenged by the discovery of giant viruses.
Giant Viruses
Mimivirus, Megavirus, and Pandoraviruses are examples of giant viruses. One of the Pandoraviruses approaches 1 mm in length and is about 0.5 mm wide, larger than many bacteria and some eukaryotic cells.
Virus Structure
A virus consists of nucleic acid surrounded by a protein coat called a capsid. A typical virus contains either DNA or RNA, not both.
RNA–DNA Hybrid Virus
In 2012, researchers discovered an RNA–DNA hybrid virus in a high temperature acidic California lake.
Virus Genome
The nucleic acid of a virus can be single-stranded or double-stranded. The virus genome typically consists of 5000 to more than 100,000 bases or base pairs. The giant viruses are exceptions, with genomes ranging from 1.9 to 2.5 million base pairs.
Capsid
The capsid is a protective protein coat that consists of protein subunits called capsomers. The capsomers determine the shape of the virus.
Helical Viruses
Helical viruses, such as the tobacco mosaic virus (TMV), appear as long rods or threads. Its capsid is a hollow cylinder made up of proteins that form a groove into which the RNA fits.
Polyhedral Viruses
Polyhedral viruses, such as the adenoviruses, appear somewhat spherical. Its capsomers are organized in equilateral triangles. The most common polyhedral structure is an icosahedron, a structure with 20 identical surface faces.
Bacteriophages
Viruses that infect bacteria are called bacteriophages, or simply phages. The T4 phage that infects the bacterium Escherichia coli consists of a polyhedral “head” attached to a helical “tail.” Many phages have this shape.
Enveloped Viruses
Some viruses, called enveloped viruses, have an outer membranous envelope that surrounds the capsid. The virus acquires the envelope from the host cell’s plasma membrane as it leaves the host cell. The viral envelope consists of phospholipids and proteins of the host’s plasma membrane as well as distinctive proteins produced by the virus itself. Some viruses produce envelope glycoproteins that extend out from the envelope as spikes.
Taxonomic Challenge
Viruses present a taxonomic challenge to biologists because they do not have the characteristics that define living organisms. They are not cellular, they do not carry on metabolic activities, and they reproduce only by taking over the reproductive machinery of other cells.
Classification Based on Host Range
Viruses can be classified based on their host range, the types of host species a specific virus can infect. They may be referred to as plant viruses, animal viruses, bacterial viruses, and so on.
ICTV Classification
The International Committee on Taxonomy of Viruses (ICTV) classifies viruses into 7 orders, 96 families, 420 genera, and more than 2600 species based on host range and other characteristics. Virus family names include the suffix -viridae.
Baltimore Classification System
This system classifies viruses based on the type of nucleic acid the virus contains, whether the nucleic acid is single-stranded or double-stranded, and how mRNA is produced. Other traits considered in viral classification are the size and shape of the virus, the presence of an envelope, and the method by which the virus is transmitted from host to host.
Viral Reproduction
Viruses reproduce only within the complex environment of the living host cells they infect. They use their genetic information to force their host cells to replicate their viral nucleic acid and make the proteins they need.
Bacteriophages
Bacteriophages, or phages, are viruses that infect bacteria. They can be cultured easily within living bacteria in the laboratory. Bacteriophages are among the most complex viruses. Their most common structure consists of a long nucleic acid molecule
(usually dsDNA) coiled within a polyhedral head. Most have a tail, which may be contractile and may function in penetration of the host cell.
Phage Therapy: Phages have been clinically used to treat infection for close to a century. Although abandoned in Western countries after the discovery of sulfa drugs and antibiotics in the 1940s, they have continued to be commonly used in member countries of the former Soviet Union to treat patients. Due to the widespread and escalating problem of bacterial resistance, phage therapy is again a focus of research in the United States as well as in Eastern Europe. Phages are being engineered to specifically destroy particular bacteria due to their ability to target specific host species. Scientists are also genetically engineering phages so that bacteria will be slower to evolve resistance to them.
Five steps of the Lytic Reproductive Cycle:
Attachment: The virus attaches to specific receptors on the host cell. This ensures that the virus infects only its specific host.
Penetration: The virus penetrates the host plasma membrane and moves into the cytoplasm. Some viruses enter the host cell intact, while others inject only their nucleic acid into the cytoplasm of the host cell.
DNA Viruses with Envelope
Poxviruses: They are large, complex dsDNA viruses that replicate in the cytoplasm of the host cell. They cause diseases like smallpox, cowpox, monkeypox, and economically important diseases of domestic fowl.
Herpesviruses: These are medium to large, enveloped dsDNA viruses that replicate in the host nucleus. They cause diseases like cold sores (herpes simplex virus type 1), genital herpes (herpes simplex virus type 2), chickenpox and shingles (herpes varicella–zoster virus), infectious mononucleosis and Burkitt’s lymphoma (Epstein–Barr virus).
DNA Viruses with No Envelope
Adenoviruses: These are dsDNA viruses that replicate in the host nucleus. They cause respiratory tract disorders (e.g., sore throat, tonsillitis), conjunctivitis, and gastrointestinal disorders in humans.
Papovaviruses: These are dsDNA viruses that cause human warts and some degenerative brain diseases, and some cancers, including cervical cancer.
Parvoviruses: These are ssDNA viruses that require a helper virus to multiply. They cause infections in dogs, swine, arthropods, rodents, and gastroenteritis in humans (transmitted by consumption of infected shellfish).
RNA Viruses with Envelope
Togaviruses: These are ssRNA viruses that can serve as mRNA. They cause diseases like Rubella (German measles).
Orthomyxoviruses: These are ssRNA viruses that serve as a template for mRNA synthesis. They cause Influenza (flu) in humans and other animals.
Paramyxoviruses: These are ssRNA viruses that cause Rubeola (measles) and mumps in humans, and distemper in dogs.
Rhabdoviruses: These are ssRNA viruses that cause Rabies.
Coronaviruses: These are ssRNA viruses that cause upper respiratory infections and SARS.
Flaviviruses: These are ssRNA viruses that cause Yellow fever, West Nile virus, and hepatitis C.
Filoviruses: These are ssRNA viruses that cause Hemorrhagic fever, including that caused by the Ebola virus.
Bunyaviruses: These are ssRNA viruses that cause St. Louis encephalitis and hantavirus pulmonary syndrome.
Retroviruses: These are ssRNA viruses that contain reverse transcriptase for transcribing the RNA genome into DNA. They cause AIDS and some types of cancer.
RNA Viruses with No Envelope
Picornaviruses: These are ssRNA viruses that can serve as mRNA. They cause diseases like Polio (poliovirus), hepatitis A (hepatitis A virus), intestinal disorders (enteroviruses), common cold (rhinoviruses), and aseptic meningitis (coxsackievirus, echovirus).
Reoviruses: These are dsRNA viruses.
Noroviruses: These are ssRNA viruses. This group is made up of strains of Norwalk virus.
Replication and Synthesis: The viral genome contains all the information necessary to produce new viruses. Once inside a host cell, the virus degrades the host-cell nucleic acid and uses the molecular machinery of the host cell to replicate its own nucleic acid and produce viral proteins.
Assembly: The newly synthesized viral components are assembled into new viruses.
Release: Assembled viruses are released from the cell. Generally, lytic enzymes, produced by the phage late in the replication process, destroy the host plasma membrane. Phage release typically occurs all at once and results in rapid cell lysis. In contrast, animal viruses are often released slowly or bud off from the plasma membrane.Animal Viruses: Unlike phages, animal viruses are often released slowly or bud off from the plasma membrane. Once released, the viruses infect other cells, and the process begins anew. The time required for viral reproduction, from attachment to the release of new viruses, varies from less than 20 minutes to more than 1 hour.
Bacterial Defense: Bacteria have mechanisms to protect themselves from phage infection. Sometimes temperate viruses become lytic spontaneously, destroying their host.
Lysogenic Cells: Bacterial cells carrying prophages are called lysogenic cells. These cells may exhibit new properties, a phenomenon known as lysogenic conversion.
Lysogenic Conversion Examples:
Corynebacterium diphtheriae: This bacterium causes diphtheria. Two strains of this species exist, one that produces a toxin (and causes diphtheria) and one that does not. The toxin-producing bacteria are infected by a specific temperate phage. The phage DNA codes for the powerful toxin that causes the symptoms of diphtheria.
Clostridium botulinum: This bacterium causes botulism, a serious form of food poisoning. It is harmless unless it contains certain prophage DNA that induces synthesis of the toxin.
Bacterial DNA Protection: A bacterial cell protects its own DNA by slightly modifying it after replication so that the restriction enzyme does not recognize the sites it would cut.
Lysogenic Cycles: In lysogenic cycles, temperate viruses integrate into the host DNA. These phages alternate between a lytic cycle and a lysogenic cycle. In a lysogenic cycle, the viral genome becomes integrated into the host bacterial DNA, becoming a prophage or provirus. When the bacterial DNA replicates, the prophage also replicates. The viral genes that code for viral structural proteins may be repressed indefinitely.
External Conditions: Certain external conditions, such as ultraviolet light and X-rays, can cause temperate viruses to revert to a lytic cycle and then destroy their host. Sometimes temperate viruses become lytic spontaneously.
Lysogenic Conversion: Bacterial cells carrying prophages are called lysogenic cells. These cells may exhibit new properties, a phenomenon known as lysogenic conversion. For example, the bacterium Corynebacterium diphtheriae, which causes diphtheria, has two strains. The strain that produces a toxin and causes diphtheria is infected by a specific temperate phage. The phage DNA codes for the powerful toxin that causes the symptoms of diphtheria. Similarly, the bacterium Clostridium botulinum, which causes botulism, is harmless unless it contains certain prophage DNA that induces synthesis of the toxin.
Virus Attachment and Entry: Viruses such as those causing herpes and rabies have a lipoprotein envelope with glycoprotein spikes that attach to a host cell. The influenza virus has rodlike glycoprotein spikes that bind with specific receptors on cells lining the respiratory tract of certain vertebrates. Some enveloped viruses enter the host cell by fusing with the plasma membrane, while others enter by endocytosis.
Viral Replication: In DNA animal viruses, replication of viral DNA and protein synthesis are similar to the host cell’s own processes. Most RNA viruses use an RNA-dependent RNA polymerase for RNA synthesis.
Retroviruses: Retroviruses are RNA viruses that have a DNA polymerase called reverse transcriptase, which transcribes the RNA genome into a DNA intermediate. This DNA integrates into the host DNA and is transcribed by host RNA polymerases. The human immunodeficiency virus (HIV) that causes AIDS is a retrovirus.
Virus Assembly and Release: After viral genes are transcribed and the viral structural proteins are synthesized, the capsid is produced, and new virus particles are assembled and released. Viruses without an outer envelope exit by cell lysis, while enveloped viruses obtain their lipoprotein envelopes by picking up a fragment of the host plasma membrane as they leave the infected cell.
Damage to the Host Cell: Viral proteins can damage the host cell in several ways, such as altering the permeability of the plasma membrane or inhibiting the synthesis of host nucleic acids or proteins. Viruses can also damage or kill their host cells by their sheer numbers, for example, a poliovirus can produce 100,000 new viruses within a single host cell.
Here are the key points from your text:
1. **Antibiotics vs Antivirals**: Antibiotics are specific for fighting bacteria and do not kill viruses. Antiviral drugs, on the other hand, have been developed to inhibit the development or replication of many types of RNA and DNA viruses.
2. **Resistance to Antivirals**: Viruses can rapidly develop resistance to antiviral drugs, making antiviral drug design and therapy a constantly changing and competitive endeavor.
3. **Example – Amantadine**: Amantadine, which inhibits penetration or uncoating of viral nucleic acids, has been effective in treating patients with influenza. However, most strains of influenza virus have become resistant to amantadine, possibly due to its common use in poultry feed in certain areas of Asia, such as China.
4. **Example – Tamiflu**: Tamiflu is another type of antiviral drug that inhibits a viral enzyme (neuraminidase) necessary for the virus to leave the host cell. Certain viral strains are becoming resistant to Tamiflu, likely due to a single spontaneous mutation.
5. **Future of Antiviral Drugs**: Many more antiviral drugs are being designed or are currently in clinical trials. Some of these drugs inhibit viral attachment to host cells, while others interfere with the replication of viral nucleic acid.
Here are the key points from your text:
1. **Antibiotics vs Antivirals**: Antibiotics are specific for fighting bacteria and do not kill viruses. Antiviral drugs, on the other hand, have been developed to inhibit the development or replication of many types of RNA and DNA viruses.
2. **Resistance to Antivirals**: Viruses can rapidly develop resistance to antiviral drugs, making antiviral drug design and therapy a constantly changing and competitive endeavor.
3. **Example – Amantadine**: Amantadine, which inhibits penetration or uncoating of viral nucleic acids, has been effective in treating patients with influenza. However, most strains of influenza virus have become resistant to amantadine, possibly due to its common use in poultry feed in certain areas of Asia, such as China.
4. **Example – Tamiflu**: Tamiflu is another type of antiviral drug that inhibits a viral enzyme (neuraminidase) necessary for the virus to leave the host cell. Certain viral strains are becoming resistant to Tamiflu, likely due to a single spontaneous mutation.
5. **Future of Antiviral Drugs**: Many more antiviral drugs are being designed or are currently in clinical trials. Some of these drugs inhibit viral attachment to host cells, while others interfere with the replication of viral nucleic acid. Three Main Hypotheses: The origin of viruses is currently explained by three main hypotheses – the progressive (or escape) hypothesis, the regressive (or reduction) hypothesis, and the virus-first hypothesis.
Progressive Hypothesis: According to this hypothesis, viruses may have originated as mobile genetic elements such as transposons or plasmids that escaped from one cell and entered another. This hypothesis is supported by the genetic similarity between some viruses and their host cells.
Regressive Hypothesis: This hypothesis asserts that viruses are remnants of cellular organisms and evolved from small cells that were parasites in larger cells. It is supported by certain bacteria that are able to reproduce only inside the cells of their hosts and by some giant viruses that have genes encoding components for protein translation.
Virus-First Hypothesis: According to this hypothesis, viruses predate or coevolved with their current cellular hosts even before the life forms assigned to the three domains diverged. Evidence for this hypothesis comes from similarities found in the protein structures of some viral capsids and in genetic similarities between some viruses that infect archaea and some that infect bacteria. Polydnaviruses: These are particles that consist of multiple circles of dsDNA encased in capsid proteins and an envelope. Each circle of DNA contains part of the virus genome. These viruses are found in ovary cells of many species of parasitic wasps.
Unique Characteristics: Polydnaviruses are unusual in that their circular DNA does not have genes for making the proteins needed to replicate and produce new viruses. Genes needed for viral replication are found in the wasp genome; the viruses can replicate only in the wasp ovary cells.
Interaction with Caterpillars: The wasp injects polydnaviruses along with her eggs into certain caterpillars. The polydnaviruses express toxins that interfere with the caterpillar’s immune defenses and development. The wasp eggs hatch and develop inside the caterpillar. The young wasps feed on the caterpillar.
Origin Hypotheses: Biologists wondered whether the polydnaviruses were really viruses or simply particles derived from wasp genes. An alternative hypothesis was that millions of years ago a particular virus infected wasps. The virus genome became integrated into the wasp genome and lost the capacity to enter virus particles. Instead, wasp DNA was incorporated into the particles.
Viral Evolution: Today’s viruses may have originated multiple times, through many mechanisms, or by a mechanism not yet discovered. They mutate constantly, producing many new alleles. They replicate rapidly, and some of their genes are incorporated into the genomes of host cells through horizontal gene transfer. In fact, viruses may provide a major source of new genes for their host cells.
Subviral Agents: These are infective agents that are smaller and simpler than viruses. Subviral agents include satellites, viroids, and prions.
Satellites: Satellites are subviral agents that depend on co-infection of a host cell with a helper virus for reproduction. For example, the agent that causes hepatitis D is a satellite that can reproduce only when the hepatitis B virus is also present.
Sputnik: Sputnik is a satellite that infects Mimivirus, which in turn infects an amoeba. Sputnik is dependent on the replication and assembly machinery set up by Mimivirus. Some researchers refer to Sputnik as a virophage, implying that it impairs the reproduction of its helper virus, Mimivirus.
Viroids: Discovered in 1971, viroids are very short, circular, single strands of naked RNA. They have no protective protein coat and no associated proteins to assist in duplication. Viroids are extremely hardy and can resist heat and ultraviolet radiation. They cause various plant diseases and are transmitted by infected pollen or seeds.
Viroid Impact: Viroids are generally found within the host-cell nucleus and appear to interfere with gene regulation. They mirror gene sequences in their hosts and silence critically important host genes. The viroid’s ssRNA replicates, forming dsRNA. The plant’s defense response cleaves this viroid RNA, producing small interfering RNAs (siRNAs). However, the viroid siRNAs then cause host ribonucleases to selectively cleave host mRNAs with complementary base sequences. This action inactivates host mRNA and silences specific host genes. The viroids themselves are resistant to RNA silencing.