10 points each
1. Define the term virus. List and describe the three main types of viral structures.
2. Why must a virus enter a living cell in order to reproduce?
3. What is a bacteriophage? What are the parts of a bacteriophage?
4. Distinguish between a lytic cycle and a lysogenic cycle.
5. Describe what happens in the following stages of bacteriophage infection: attachment and penetration, virion assembly, and release of virions.
6. How does Covid-19 spread? What are its symptoms?
7. What is the name for the virus that causes Covid-19? How does the virus attach to a cell? What kinds of cells can it attach to?
8. Describe two ways that the virus can enter a cell.
9. Explain how the virus replicates within the cell.
10. How are mutations of the genetic material of the virus caught and corrected by the virus?
A virus is an infectious, obligate intracellular parasite comprising genetic material (DNA or RNA), often surrounded by a protein coat, sometimes a membrane.
Infectious means capable of causing disease. The virus must enter a host cell in order to reproduce. In doing so, it can harm or kill the cell. Viruses cause a number of major diseases.
Obligate means that they must. Viruses must enter a living cell in order to reproduce. Viruses cannot replicate on their own. Viruses do not have protein synthesizing machinery of their own. The nucleic acid of the virus takes over the synthesizing machinery of the host and directs it to make new components of the virus, not the normal components of the cell it infects.
Intracellular means within the cell.
A parasite lives at the expense of its host.
Viruses can have DNA or RNA as the genome. Viruses are unique because nowhere else do we see RNA as the genome.
Surrounded by a Protein Coat or a Membrane
The vast majority of viruses have a protein coat. Some viruses have a membrane, for example coronaviruses.
The study of viruses is virology.
Viral particles are called virions.
Are viruses alive?
When a virus is outside of a living cell it cannot reproduce on its own. It does not appear to be living. It is inert. Life processes such as metabolism, growth, reproduction, and movement are not detectable.
When viruses enter a living cell, they are able to replicate. The viral genome directs the infected cell to synthesize new viral genetic material and protein coats. They assemble to produce new intact viruses. These can leave the cell and be able to infect other cells. So does this mean that viruses are alive within the cell? Although being able to reproduce is certainly an important characteristic of life, is it enough to make viruses alive? If viruses can control the metabolism of a host cell but can’t metabolize on their own, can we consider them alive? It might be safer to say that viruses are on the borderline between the living and the nonliving. To read more on this topic, I would recommend the Scientific American article “Are Viruses Alive?” by Luis P. Villarreal in the August 8. 2008 issue.
Are viruses organisms?
Viruses are not considered organisms, because they are not cellular, lack independent metabolism, and cannot replicate except when they are inside of a living cell.
Size of Viruses
Viruses are very small. At one time viruses were defined on the basis of being able to pass through a 0.2 micron porcelain filter.
The definition of viruses as particles 0.2 µm or less has become obsolete based on the discovery of a group of very large viruses. They are the Giant viruses, some of which are larger than typical bacteria. “They have extremely large genomes compared to other viruses and contain many unique genes not found in life forms (Wikipedia https://en.wikipedia.org/wiki/Giant_virus).” Megavirus was isolated from a water sample collected in April 2010 off the coast of Chile. Megavirus has a capsid diameter of 440 nanometres. The genome of Megavirus is a linear, double-stranded molecule of DNA composed of 1,259,197 base pairs. Megavirus infects amoebas. Pandoravirus is a group of giant viruses discovered in 2013 living in Acanthamoebae. They live mostly in marine environments, where they prey upon organisms living in plankton. They have also been found in freshwater lakes. Pandoravirus is oval in shape and has a capsid length of approximately 1 µm. This makes it the second-largest virus that has been discovered. It has the largest viral genome, consisting of double-stranded DNA with a length of 2.5 million base pairs. Mimivirus was discovered in the amoeba Acanthamoeba polyphaga . The virus was observed in a Gram stain and mistakenly thought to be a Gram-positive bacterium (https://en.wikipedia.org/wiki/Mimivirus).” It was later identified as a virus. (https://en.wikipedia.org/wiki/Mimivirus).” Mimivirus has a capsid diameter of 400 nm. The mimivirus genome is a linear, double-stranded molecule of DNA with 1,181,404 base pairs in length. Analysis of its genome revealed the presence of genes not found in any other viruses, and other genes previously thought to be found only in cellular organisms. Mimivirus is within the size range of bacteria, such as Rickettsia. It has a genome is similar in size to that of several bacteria and codes for products not found in other viruses including a kind of collagen. In addition, mimivirus has genes coding for nucleotide and amino acid synthesis, which are usually not found in viruses. They lack genes for synthesizing ribosomal proteins, and are therefore dependent on a host cell for protein translation and energy metabolism. These findings have led to a suggestion that Mimivirus is related to a type of DNA virus that emerged before cellular organisms and may have played an important role in the early evolution of life. Pithovirus was discovered in 2014 as a viable specimen recovered from a 30,000-year-old ice core sample extracted from permafrost in Siberia, Russia. Pithovirus is the largest virus that has been discovered to date. It has a length of 1.5 µm and a diameter of 0.5 µm. Its genome consists of circular double-stranded DNA containing 610,000 base pairs.
Structure of Viruses
Viruses are not composed of cells; they lack cytoplasm or cellular organelles. A complete virus particle, known as a virion is composed of a core of nucleic acid surrounded by a protein coat. Most viruses are surrounded by a protein coat or capsid that surrounds their nucleic acid core. The capsid is formed from identical protein subunits called capsomeres. “The capsid is made from proteins encoded by the viral genome and its shape serves as the basis for morphological distinction https://en.wikipedia.org/wiki/Virus.” Some viruses are surrounded by a membrane. Viruses contain a single type of nucleic acid, which is either DNA or RNA. “The viral genome may be linear or circular, and single-stranded or double-stranded (Mason et al.).”
The most common types of viral structures are helical and icosahedral.
Helical viruses are composed of a single type of capsomere stacked around a central axis forming a helical structure, with a central cavity, or tube inside. The genetic material is typically single-stranded coiled RNA, or in some cases, single-stranded DNA.
Most animal viruses have an icosahedral structure. An icosahedron is a polyhedron with 20 faces. Each face is an equilateral triangle.
“Some viruses, like the T-even bacteriophage, are complex, with an icosahedral head and a helical tail (Mason, et al.).” The bacteriophage has a hexagonal base plate with protruding protein tail fibers.
The Replication of Viruses
Viruses must enter a living cell in order to reproduce. The virus must be specialized to recognize the surface of the cell that it infects. It must then attach to a specific host cell. There may be specific structures that are used for this purpose. For example in bacteriophages there are protein fibers extending from the tail section of the virus that are used for attachment to the host bacterial cell that it infects. Next, the virus must penetrate the cell and enter it. Following their entry into the cell, the virus takes over the metabolic machinery within the cell responsible for replication of its genetic and protein synthesis. Viruses lack the ribosomes and the enzymes needed for the synthesis of protein as well as the enzymes needed for the replication of nucleic acids. As a result, viruses must exist as obligate intracellular parasites and produce new viruses by expressing their genome to direct the host’s synthesizing apparatus to produce new viral nucleic acids and proteins instead of the normal products of the host. The synthesis of viral components is followed by assembly of the components into new intact viruses. The viruses may then be released from the cell. This involves lysis, a process that kills the cell by bursting its membrane or cell wall, if present. The freed virus can then go on to infect other cells. Some viruses undergo a lysogenic cycle where the viral genome is incorporated by genetic recombination into a specific place in the host’s chromosome. The viral genome is then known as a “provirus” or, in the case of bacteriophages a “prophage”. Whenever the host divides, the viral genome is also replicated. The viral genome is mostly silent within the host. At some point, the provirus or prophage may give rise to active virus, which may lyse the host cells (https://en.wikipedia.org/wiki/Virus).
“Viral hosts include every kind of organism that has been investigated for their presence. They infect fungal cells and protists, as well as prokaryotes, animals, and plants. However, each type of virus can replicate in only a very limited number of cell types. Bacterial viruses such as T4 do not infect human cells (Mason et al.)”
“Bacteriophage structures are diverse, but the vast majority of characterized phage share some common characteristics. Many phage have an icosahedral, head structure made of repeat protein subunits known as the capsid. This head structure contains the viral genome. The primary difference in phage are the presence or absence of a ‘tail’ structure https://www2.le.ac.uk/projects/vgec/highereducation/topics/microbial-genetics-1/bacteriophage.
Replication of T4 Bacteriophage
A bacteriophage is a virus that infects a bacterial cell. “Bacteriophages may have a lytic cycle or a lysogenic cycle. With lytic phages such as the T4 phage, bacterial cells are broken open (lysed) and destroyed after immediate replication of the virion. As soon as the cell is destroyed, the phage progeny can find new hosts to infect https://en.wikipedia.org/wiki/Bacteriophage.” In contrast, the lysogenic cycle does not result in immediate lysing of the host cell. Those phages able to undergo lysogeny are known as temperate phages. Their viral genome will integrate with host DNA and replicate along with it, relatively harmlessly, or may even become established as a plasmid. The virus remains dormant until host conditions deteriorate, perhaps due to depletion of nutrients, then, the endogenous phages (known as prophages) become active. At this point they initiate the reproductive cycle, resulting in lysis of the host cell. As the lysogenic cycle allows the host cell to continue to survive and reproduce, the virus is replicated in all offspring of the cell. An example of a bacteriophage known to follow the lysogenic cycle and the lytic cycle is the phage lambda of E. coli.
Attachment and Penetration
Bacterial cells are surrounded and protected by a cell wall of polysaccharides. To enter the bacterial host cell, the bacteriophage must bind to specific receptors on the surface. “This specificity means a bacteriophage can infect only certain bacteria bearing receptors to which they can bind, which in turn, determines the phage’s host range https://en.wikipedia.org/wiki/Bacteriophage.” The virus releases enzymes that break down polysaccharides to create a point of entry. The bacteriophage then acts like a little hypodermic needle to inject its genetic material through the opening into the bacterial cell. After contacting the appropriate receptor, the tail fibers flex to bring the base plate closer to the surface of the cell. Once attached completely, the tail contacts, injecting genetic material through the bacterial membrane. Within minutes after entering the host cell, the mRNA of the bacteriophage begins directing the ribosomes of the host to translate the viral mRNA into viral proteins, instead of the normal proteins of the bacterial cell. In the case of RNA-based phages, one of the protein enzymes that is synthesized early in the process is RNA replicase, an enzyme needed to produce new copies of the viral RNA genome.
Following the synthesis of the viral nucleic acid and protein components, they are assembled into intact new viruses. “The base plates are assembled first, with the tails being built upon them afterward. The head capsids, constructed separately, will spontaneously assemble with the tails https://en.wikipedia.org/wiki/Bacteriophage.”
Release of Virions
Phages are usually released from the bacterial cell by lysis, which is completed by an enzyme called endolysin, which attacks and breaks down the cell wall peptidoglycan.
Coronavirus disease 2019 (COVID-19) is a contagious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The first known case was identified in Wuhan, China, in December 2019. The disease has since spread worldwide, leading to an ongoing pandemic. https://en.wikipedia.org/wiki/COVID-19
Symptoms of COVID-19 are variable, but often include fever, cough, headache, fatigue, breathing difficulties, and loss of smell and taste. Symptoms may begin one to fourteen days after exposure to the virus. At least a third of people who are infected do not develop noticeable symptoms. Of those people who develop noticeable symptoms enough to be classed as patients, most (81%) develop mild to moderate symptoms (up to mild pneumonia), while 14% develop severe symptoms (dyspnea, hypoxia, or more than 50% lung involvement on imaging), and 5% suffer critical symptoms (respiratory failure, shock, or multiorgan dysfunction). Older people are at a higher risk of developing severe symptoms. Some people continue to experience a range of effects—known as long COVID—for months after recovery, and damage to organs has been observed. Multi-year studies are underway to further investigate the long-term effects of the disease. https://en.wikipedia.org/wiki/COVID-19
The virus that causes COVID-19 spreads mainly when an infected person is in close contact with another person. Small droplets and aerosols containing the virus can spread from an infected person’s nose and mouth as they breathe, cough, sneeze, sing, or speak. Other people are infected if the virus gets into their mouth, nose or eyes. The virus may also spread via contaminated surfaces, although this is not thought to be the main route of transmission. The exact route of transmission is rarely proven conclusively but infection mainly happens when people are near each other for long enough. People who are infected can transmit the virus to another person up to two days before they themselves show symptoms, as can people who do not experience symptoms. People remain infectious for up to ten days after the onset of symptoms in moderate cases and up to 20 days in severe cases. https://en.wikipedia.org/wiki/COVID-19
Coronavirus disease 2019 (COVID-19) spreads from person to person mainly through the respiratory route after an infected person coughs, sneezes, sings, talks or breathes. A new infection occurs when virus-containing particles exhaled by an infected person, either respiratory droplets or aerosols, get into the mouth, nose, or eyes of other people who are in close contact with the infected person. During human-to-human transmission, an average 1000 infectious SARS-CoV-2 virions are thought to initiate a new infection. https://en.wikipedia.org/wiki/COVID-19
COVID-19 can affect the upper respiratory tract (sinuses, nose, and throat) and the lower respiratory tract (windpipe and lungs). The lungs are the organs most affected by COVID-19 because the virus accesses host cells via the enzyme angiotensin-converting enzyme 2 (ACE2), which is most abundant in type II alveolar cells of the lungs. ] The virus uses a special surface glycoprotein called a “spike” (peplomer) to connect to ACE2 and enter the host cell. https://en.wikipedia.org/wiki/COVID-19
Loss of smell results from infection of the support cells of the olfactory epithelium, with subsequent damage to the olfactory neurons. https://en.wikipedia.org/wiki/COVID-19
The virus also affects gastrointestinal organs as ACE2 is abundantly expressed in the glandular cells of gastric, duodenal and rectal epithelium as well as endothelial cells and enterocytes of the small intestine. https://en.wikipedia.org/wiki/COVID-19
The virus can cause acute myocardial injury and chronic damage to the cardiovascular system. https://en.wikipedia.org/wiki/COVID-19
Coronaviruses (CoVs) are enveloped positive-sense single-stranded RNA viruses. They infect humans, other mammals and avian species, including livestock and companion animals.
Human coronaviruses cause seasonal and usually mild respiratory tract infections associated with symptoms of the ‘common cold’. Other coronaviruses, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV-2, are highly pathogenic. They infect upper respiratory tract cells, bronchial cells and lung cells and can develop into severe, life-threatening respiratory diseases. There is as yet no treatment has been approved to date. Nature 10 28 2020
The virus that causes Covid-19 is a novel coronavirus known as SARS-CoV-2. It was first isolated from three people with pneumonia connected to the cluster of acute respiratory illness cases in Wuhan, China. SARS-CoV-2 is thought to have arising in animals. Pathologists describe this as a zoonotic origin. Its genetic sequence is closely related to that found in horseshoe bats.
It is a positive-sense single-stranded RNA (+ssRNA) virus, with a single linear RNA segment.
Cell Infection and Replication by Sars Co-V-2
Attachment and Entry
To infect a cell, the Sars Co-V-2 virus must first recognize and attach to specific molecules on the surface of the cell. The spike proteins on the envelope surface of the virus attach to binding sites, known as receptors on the surface of the host cell. The receptor on the surface of the host cell is angiotensin-converting enzyme 2 (ACE2). The Sars Co-V-2 virus is particularly dangerous because these ACE2 receptors are found in many cells, enabling the virus to infect cells in the lower respiratory tract, heart, kidney, liver, brain, gut lining and stomach, and blood vessels.
There are two ways that the Sars Co-V-2 virus can enter the cell. These include: 1) fusion of the viral envelope and the cell membrane and 2) formation of an endosome
Fusion of the Viral Envelope and the Cell Membrane
The viral envelope and the cell membrane fuse. This is followed by the viral contents being emptied into the cell.
Formation of an Endosome
The attachment of the virus sets off a process in which the area of the cell membrane below the virus invaginates, or caves in, carrying the virus into the cell. The membrane then pinches off, forming an endosome, a membrane-coated, liquid-containing capsule, with the virus inside.
Viral Gene Expression, RNA and Protein Synthesis
After the genomic single-stranded RNA of the virus is uncoated and enters the cell, it will commandeer the metabolic machinery of the cell and direct it to produce new viral RNA and proteins required for the replication of the virus. These include an enzyme that replicates the RNA of the viral genome, an RNA to RNA polymerase. Our cells lack a polymerase that can make RNA copies from RNA. The SARS-CoV-2’s genome, though, does carry a gene coding for an RNA-to-RNA polymerase. The polymerase can be produced by translating the viral RNA using the ribosomes of the host. The polymerase will function to copy the viral RNA producing new RNA viral genomes.
The viral genome is replicated to produce full-length negative-sense genomic copies, which function as templates for the generation of new positive-sense genomic RNA. These newly synthesized genomes are used for translation to generate more non-structural proteins and new viral replication and transcription complexes or are packaged into new virions. Nature 10 28 2020
The virus must also program the synthesis of proteins that will be incorporated into new virus particles.
The RNA of the viral genome is translated to produce non-structural proteins that form the viral replication and transcription complex. Sixteen non-structural proteins are produced. Some of the non-structural proteins perform functions such as modulating intracellular membranes, host immune evasion and providing cofactors for replication. Others carry out the enzymatic functions involved in RNA synthesis, RNA proofreading and RNA modification.
In general, coronavirus structural proteins assemble and assist in the budding of new virions at the endoplasmic reticulum (ER)-to-Golgi compartment that are suggested to exit the infected cell by exocytosis
As the initial RNA strand of the virus is copied, copying errors or mutations can occur. The Sars Co-V-2 virus however produces a proofreader protein that catches these errors and chops out the incorrect sequence and inserts the correct one.
During the early coronavirus replication cycle, interactions between non-structural proteins produced by the virus and host cell factors initiate the formation of replication organelles that create a protective microenvironment for viral RNA replication and transcription. Structural proteins can translocate into endoplasmic reticulum (ER) membranes and interact with newly produced genomic RNA. This is followed by budding into the lumen of secretory vesicular compartments.
Finally, virions are secreted from the infected cell by exocytosis.