Ch 5 Viruses

Symmetry

-Capsids often exhibit either helical or icosahedral shapes. In all viruses, one or more viral proteins surround the genome, forming the nucleocapsid or, more simply, the capsid. Biochemical and genetic studies have shown that the capsid of all viruses consists of many symmetrically arranged subunits, or capsomeres. In turn, each capsomere consists of one or more polypeptides. The capsids of some viruses, like tobacco mosaic virus (see Figure 5.3), exhibit a helical morphology, in which the capsomeres form a helix and the capsid resembles a hollow tube. The capsids of other viruses exhibit an icosahedral morphology, in which the capsomeres form an icosahedron, or 20-sided polygon, with each capsomere making up a face of the icosahedron. Many bacteriophages, like T4 (see Figure 5.3), exhibit both helical and icosahedral morphologies, containing an icosahedral "head" and a helical "tail." The giant viruses described earlier and a few animal viruses, most notably the poxviruses, have a less well-defined capsid morphology.

•Replication cycle: Entry What are challenges infecting bacteria, plants and fungi?

-Entry is arguably the most important part in the viral replication cycle. -Mechanisms for entry vary depending on the host cell. •Animal viruses don't have to contend with a cell wall structure. •Plant, fungal, and bacterial viruses do.

Viral Envelopes where do they get them when and how? Can you pick out enveloped and naked viruses from EM pictures? Complex structure of bacteriophages Pox viruses are also complex and their capsid look like a basket weave.

-If a plasma membrane surrounds the nucleocapsid, the virus is "enveloped." -If there is no plasma membrane, the virus is "naked." For many viruses, like poliovirus, complete infectious virions consist only of a capsid surrounding a genome and are referred to as non-enveloped, or naked, viruses. For other viruses, a cell-derived membrane, called the viral envelope, surrounds the nucleocapsid. For enveloped viruses, the viral envelope and its associated proteins usually are required for successful entry into a new host cell. Without an intact envelope, the proteins needed for viral attachment are absent or non-functional, and the virus is rendered non-infectious. These viral attachment and entry proteins are transcribed and translated from the viral genome in the infected host cell and are inserted into the host cell membrane that is destined to become the viral envelope. In acquiring an envelope, the virus also may take with it some host cell-derived membrane proteins. These proteins may help disguise the virus from an immune attack by making it appear similar to a host cell, at least on the outside. Even though this strategy has an obvious advantage to the virus, the drawback is that the envelope typically can be degraded in the external environment through desiccation and exposure to chemicals.

•Replication cycle: Entry into plant cells know different ways your plants get viral infections

-Often depends on some damage to the plant tissues to open a spot in the cell wall •Insects feeding on plants •Wind damage •Hail/rain damage •Fire damage •Human-induced damage

You will need to understand the genome, capsid, nucleocapid, capsomere, naked vs enveloped viruses termimology.

-Single or double-stranded D N A or R N A -Protein shell (capsid) around genome composed of many capsomere proteins •Capsid and genome together = nucleocapsid -Possible envelope (plasma membrane around capsid)

on occasion, a lab worker may contaminate themselves but these are rare isolated events.

-Smallpox may have been responsible for the death of Ramses V in Egypt -The last case of naturally acquired smallpox occurred in 1977, and the world was declared smallpox-free in 1980.

Electron Microscopy EM is one tool we use to quickly identify viruses

-The first step in identification rests on visual observation of viral morphology (not infallible). It shouldn't come as any surprise, then, that poliovirus virions and smallpox virus virions can be differentiated easily by electron microscopy. Electron microscopy is not just useful for differentiating vastly different viruses. Many viral groups have distinctive shapes. As a result, electron microscopy can be a fairly useful tool in identifying viruses. Not surprisingly though, electron microscopy also can be fairly imprecise. Many viruses look similar, at least superficially or to the untrained eye

•What's next for virology?

-Unsurprisingly, virology and medicine are closely involved. -Virology examines cancer-causing oncoviruses. -Virology examines cancer-destroying oncolytic viruses. -Viruses can even be exploited to deliver working copies of genes to replace damaged versions (gene therapy, experimental).

Helical Symmetry What type of viruses are often helical? WHY? because all known animal viruses with helical nucleocapsid symmetry has an envelope surrounding the nucleocapsid. virion can be naked or envelope and it is a term that just means complete and can infect Helical symmetry of tobacco mosaic virus (TMV) A viral capsid exhibits helical symmetry if it can be rotated about its long axis and shows no distinguishing features

-Viral capsids can sometimes take on irregular or complex shapes. The simplest structural arrangement found in virus capsids is that of a single polypeptide that directly coats the genome in a repetitive manner, as occurs for tobacco mosaic virus (TMV). The individual capsid proteins interact at regular intervals with the genome and also associate with each other, causing the structure to twist and take on a tube-like coiled form, much like a spiral staircase (Figure 5.5). A similar arrangement occurs in influenza viruses. Multiple copies of a single viral protein, known as nucleoprotein, or NP, and a viral polymerase complex associate with each segment of RNA, resulting in eight separate nucleocapsids within each virus particle. This helical symmetry gives viruses like TMV a filamentous, fiber-like, or rod-shaped morphology. In all viruses with helical capsid symmetry, there is an intimate association between the genome and the capsid proteins. Many phages and plant viruses consist of just helical nucleocapsids. In these viruses, the helical nucleocapsid is the virion, or complete viral particle. However, all known animal viruses with helical nucleocapsid symmetry, like influenza virus, have an envelope surrounding the nucleocapsid (Figure 5.6).

•Are viruses the simplest pathogens? Know all of the Virus-like Particles and what they look like and infect

-Viroids: -Consist only of naked R N A -Are extremely small (less than 400 nucleotides) -Have a high degree of internal complementarity -Are resistant to ribonucleases -So far, are only observed to cause disease in plants

5.4 Fact Check

1. Describe the strategies used to name viruses. 2. What viral attributes are considered by the ICTV when classifying viruses? 3. How does the Baltimore classification scheme categorize viruses?

5.1 Fact Check 1. Identify the different types of viral genomes. 2. Contrast the capsid structures of helical and icosahedral viruses. 3. What are the different ways in which viruses attach to host cells? 4. Compare the entry into host cells of enveloped and non-enveloped viruses.

3. fusion, endocytosis (non-enveloped or enveloped) 4. in both non-enveloped & enveloped viral cells enter through endocytosis and has an endosome surround it. non-enveloped viruses has a nucleocapsid escape into the cytoplasm and uncoats to release the genome. enveloped viruses wait for the low pH of the endosome to initiate fusion of viral envelopes with endosome membrane. the nucleocapsids are then released.

Icosahedral Symmetry what do they look like and what are examples?

A geometrically perfect icosahedron has 20 faces and 12 vertices forming a closed sphere, and each face of the icosahedron is an equilateral triangle. Rhinovirus, which causes the common cold, uses three different polypeptides to construct its capsid.

Complex Symmetry

Although some viruses of bacteria exhibit simple helical or icosahedral capsid symmetry, most of the known bacteriophages exhibit a more complex structure. These viruses possess an icosahedral head, which contains the genome, and a helical tail (Figure 5.8). This structural arrangement has not been observed among any viruses of plants or animals. As we will see in the next section, this structure is intimately tied to the way in which phages infect their host cells.

Viral Replication

Attachment (adsorption) of the virus to a susceptible host cell Entry (penetration) of the virion or its nucleic acid Synthesis of virus nucleic acid and protein by cell metabolism as redirected by virus Assembly of capsids and packaging of viral genomes into new virions (maturation) Release of mature virions from host cell

be able to write ou the steps of viral replication. Later we will use this to discuss anti-virals KNOW THEM

FIGURE 5.12 Process Diagram: General steps in a viral replication cycle Despite the many differences that exist in viral replication strategies, the underlying process is the same for all viruses. This schematic depicts the replication of a virus with a DNA genome.

how ebola virus was named

FIGURE 5.24 Ebola River, Zaire The first documented cases of Ebola infection occurred near the Ebola River. As a result, the virus was named Ebola virus

You will need to be able to give me the Baltimore classification based upon genome.

How do viruses replicate? -Replication Strategies depends on the type of nucleic acid they contain. -dsDNA viruses- -ssDNA viruses- -ssRNA viruses- -Positive sense -Negative sense -dsRNA viruses that use reverse transcription -dsDNA viruses that use reverse transcription

5.4 Diversity of Viruses

However, the classification of viruses is problematic. First, the evolutionary history and relatedness of viruses is still poorly understood. Second, no single genetic yardstick, comparable to the ribosomal RNA sequences of bacteria, archaea, and eukarya, exists for establishing relationships between viruses of mammals or between the viruses of mammals and the viruses of plants, insects, eukaryal microorganisms, bacteria, or archaea. No single gene exists in all viruses

WHAT? HOW?

It appears that viroid genomes do not contain any genes; consequently, viroids do not produce any proteins. So, what enzymes are involved in the replication of the viroid genome? Several studies using inhibitors of various cellular polymerases indicate that one or more of the host cell RNA polymerases may be involved. The pathology associated with these agents may result from this utilization of the host RNA polymerases. It is postulated that replication of the viroids may divert essential resources away from cellular transcription, thereby adversely affecting the health of the plant.

why? What would this look like on a EM picture? (empty capsids outside) T-phages are interesting. How do they penetrate the cell wall? How do some bacteria penetrate and secrete proteins directly? Sec III -sound familiar. FIGURE 5.11 Process Diagram: Entry mechanisms of bacteriophages Following attachment to a host cell, a series of conformational changes occur in the protein units of the tail, allowing the DNA to move from the capsid head directly into the cytoplasm of the host cell. The virus particle does not actually enter the host cell.

Like animal viruses, bacteriophages interact with various components of the bacterial surface, including specific polysaccharide residues. With the action of specific enzymes, the phage core proteins penetrate the cell membrane, and the bacteriophage injects its genetic material into the host cell, much like a syringe injects its contents. Thus, the viral proteins remain outside the cell, never crossing the cell membrane

FIGURE 5.32 Hepatitis delta virus Hepatitis D virus (HDV) is an enveloped virus-like agent with a circular single-stranded RNA genome with extensive base-pairing. The genome is associated with the large form of the hepatitis delta antigen, encoded by HDV. HDV only can replicate in cells that are also infected with hepatitis B virus (HBV). HBV provides the proteins necessary for the HDV envelope.

Like satellite viruses, virophages only replicate in host cells co-infected with a helper virus. Unlike satellite viruses, the replication of these infectious agents is detrimental to the helper virus.

structure/function. ssRNA is not stable, wrapping it with proteins protects it but also explain why it is a helix. If I give you the type of genetic material can you predict the shape?

Most viruses with helical capsid symmetry contain single-stranded RNA genomes. There probably are molecular reasons for this pairing. Single-stranded RNA is quite unstable and subject to rapid degradation; directly coating the genome in protein helps to protect it.

why not directly?

Plant viruses often enter cells through disruptions in the cuticle covering of the plant tissue. Farm machinery, grazing animals, or feeding insects, for example, can cause these disruptions. Once inside a cell, the viral capsid undergoes a disassembly process, thereby releasing its genome

Satellite Viruses and RNAs

Satellite viruses and satellite RNAs represent other classes of subcellular infectious agents. Like viroids, these agents both contain small RNA genomes and infect plants. Satellite viruses and RNAs differ from viroids in two basic ways. First, satellite viruses and RNAs cannot undergo autonomous replication within a host cell. Rather, the replication of these agents depends on functions provided by a helper virus that coinfects the host cell. Second, these agents contain a protein coat that encapsulates the RNA genome. The source of this protein provides the major distinguishing feature between satellite RNAs and satellite viruses. For satellite RNAs, this coat consists of a protein encoded by the helper virus. On the other hand, satellite viruses possess a gene that encodes their own capsid protein. A human infectious agent very similar to satellite viruses has been identified. Hepatitis delta virus (HDV) contains a single-stranded RNA genome approximately 1,700 nucleotides in length that, like viroids, contains many regions of intrastrand complementarity. HDV can replicate and form infectious progeny only in a cell that is co-infected with hepatitis B virus (HBV).

The ICTV Classification Scheme we call them strains or variants

The ICTV Classification Scheme In 1971, the International Committee on Taxonomy of Viruses (ICTV), a committee of the International Union of Microbiological Societies, developed an official, comprehensive classification system for viruses (see Appendix C). However, it should be noted that the concept of species is poorly defined for viruses. Certainly, the standard definition of a species as a group of interbreeding individuals does not apply to viruses or, for that matter, bacteria or archaea.

Who is Walter Reed? What did he show? How did Yellow fever change US History? Walter Reed was a virologist and he identified yellow fever which was the first human disease caused by a virus transmitted by mosquitoes. we will discuss yellow fever but Wessner isn't from LA so he missed some critical history here!

The advances in this new field have been amazingly rapid. By 1901, Walter Reed and colleagues demonstrated that a human disease—yellow fever—was caused by a virus and could be transmitted by mosquitoes (Figure 5.2). During the early part of the twentieth century, Frederick Twort and Felix d'Herelle described viruses that infect bacteria, termed bacteriophages ("bacteria eaters") by d'Herelle -Walter Reed showed in 1901 that a human disease, yellow fever, was caused by a virus transmitted by mosquitoes..

FIGURE 5.10 Process Diagram: Entry mechanisms of animal viruses Following attachment to a host cell, some part of the virion or viral genome must gain access to the cell. a. Non-enveloped viruses like rhinovirus often enter through endocytosis. b. Enveloped viruses like HIV undergo a membrane fusion event at the cell surface. c. Enveloped viruses like influenza first enter the cell via endocytosis. A fusion event between the viral envelope and vesicle membrane then occurs. •Replication cycle: Entry into animal cells You need to know the different ways virus enter host cells and these examples. We will see this again in Chapter 8.

Three methods used -endocytosis in vesicle; endosome aids in viral uncoating (rhinovirus, influenza virus) -fusion of the viral envelope with host membrane; nucleocapsid enters -injection of nucleic acid

know which organization are the only ones authorized to name viruses.

To avoid stigmatizing people or regions by linking them to disease names, researchers have become more intentional about naming new infectious diseases. Indeed, in 2015, the World Health Organization published a document that outlines its recommendations for this process. First, names should contain generic or specific descriptive terms, a reference to the causative pathogen, or an indication of when the disease was first reported. Second, the name should not include geographic locations, people's names, or cultural references. Thus, in accordance with these best practices, the new coronaviral disease first observed in December 2019 became known as COVID-19 (coronavirus disease 2019). Because the causative agent is closely related to the SARS virus, it became known as SARS-CoV-2.

Replication Cycle know the various replication methods-entry, uncoating, etc. I did not highlight all of these here so you can read about them.

To enter an appropriate host cell, most animal viruses bind to the cell. Usually, this binding occurs through a specific interaction between the viral attachment protein, a protein or proteins present on the surface of the virus that aid in binding to a host cell, and the receptor, a protein present on the surface of the host cell with which the attachment protein interacts. For enveloped viruses, the attachment protein generally resembles a spike embedded within the lipid bilayer envelope of the virion. For some non-enveloped viruses, like the adenoviruses, the attachment protein exists as a spike protruding from the vertices of the icosahedron (see Figure 5.7b). For other non-enveloped viruses, like poliovirus, the cellular receptor interacts with amino acid residues that exist in an indentation, or canyon, within the capsid.

what does that mean and how is that different from RNA virus or other Virus-like particles? so if they have internal sequences that complement each other- what is going to happen?

Today, a number of viroids that infect plants have been isolated and characterized. All of them share several characteristics and differ from viruses in significant ways. Viroids: -consist only of naked RNA, - are extremely small (less than 400 nucleotides), - exhibit a great deal of internal sequence complementarity, - exhibit increased resistance to ribonucleases, enzymes that degrade RNA.

This is too complicated. Know that -virdae is the family of viruses

members of a virus family (with the suffix- viridae)

Prions know how proteins are thought to replicated by themselves and the diseases they cause

prions probably represent the most unusual infectious agents identified to date. Prions, or proteinaceous infectious particles, appear to contain no DNA or RNA. Despite the absence of a genome, these agents can replicate, in a manner of speaking, in the host, causing disease. In fact, researchers now recognize prions as the causative agents of several diseases, including kuru and Creutzfeldt-Jakob disease (CJD) in humans, scrapie in sheep, and bovine spongiform encephalopathy (also referred to as mad cow disease) in cattle (Figure 5.33). Collectively, these diseases are referred to as transmissible spongiform encephalopathies (TSEs), progressive neurological diseases characterized by impaired mental functions and sponge-like holes in the brain. In humans, an inherited form of CJD has been observed. An infectious form, vCJD, also has been observed. Moreover, brain homogenates passed through a 0.2-μm filter still were infectious, indicating that the responsible agent probably was not a bacterium. Experiments by Stanley Prusiner at the University of California, San Francisco and others demonstrated that treatments that destroy nucleic acids did not alter the infectivity of the agent.

how do enveloped viruses attach and enter? what are the two possible mechanism?

through endocytosis; an endosome forms inside the virus of the cell and the low pH of the endosome initiates fusion of the viral envelope with the endosome membrane. The nucleocapsids are released.

how do non-enveloped viruses attach and enter?

through endocytosis; an endosome forms within the virus inside

What is a virus? what is a virus? what are the parts of its structure? How are they different based upon genetic material? What is their morphology? How do they replicate? How does scientists "know" viruses have been around and that Ramses may have had smallpox?

viruses are small subcellular particles that can replicate only within living host cells. As a result, viruses are obligate intracellular parasites; they cannot replicate independently. They consist of an RNA or DNA genome enclosed within a protective protein shell, or capsid. Together, the genome and capsid compose the nucleocapsid. Some viruses also contain a viral envelope, a host cell-derived membrane that surrounds the capsid. During the production of new virus particles, all viruses require host cell enzymes for translation. Many viruses also require host cell enzymes for various aspects of transcription and/or genomic replication. Because of this dependence on the host cell, all viruses have a mechanism for entering a host cell, and newly formed viruses must possess a mechanism for then exiting the cell. As we will see later in this chapter and in Chapter 9, different viruses carry out these basic activities in very different ways. To begin our investigation of viruses, we will explore the history of virology. -History of virology. -Viral diseases have plagued humans since before we even knew what they were (smallpox in Egypt). -It began as science in the late 1800s, when infectious tobacco mosaic virus was isolated in a filtered, bacteria-free fluid by Ivanovski, then Beijerinck.

PRIONS- fun stuff- know how they are thought to be generated. know this FIGURE 5.34 Process Diagram: Model of prion replication When pathogenic PrPSc (scrapie) protein molecules come in contact with PrPc (normal) molecules, they cause the PrPc molecules to change shape, becoming PrPSc molecules. In this fashion, the prion protein, devoid of any nucleic acid, can replicate and function as an infectious agent

•Prions (proteinaceous infectious particles): -No nucleic acid, no genes—just protein -Very different "infectious" agent -Responsible for transmissible spongiform encephalopathies (T S E s), such as mad cow disease •Prions (proteinaceous infectious particles): -Replication method still unclear -Thought to revolve around conversion of protein conformations from normal to abnormal form over time

Attachment (adsorption) why is this important to you know in a pandemic!!

•Specific receptor attachment •Receptor determines host preference -may be specific tissue (tropism) -may be more than one host -may be more than one receptor -may be in lipid rafts providing entry of virus

what makes up a virus (virion)?

•Viral structure -Capsid: the protein shell that surrounds the genome of a virus particle •Capsomere: subunit of the capsid -Smallest morphological unit visible with an electron microscope -arranged in a precise and highly repetitive pattern around the nucleic acid -helical, icosahedral, or complex

Know all of the Virus-like Particles and what they look like and infect.

•Virophages -Also require a helper virus for their replication. However, replication of the virophage damages the helper virus. -Play an important role in the lateral transfer of genetic material from organism to organism.

The Baltimore Classification Scheme who was this named after? KNOW THIS

•Virus classification: The Baltimore classification system -Developed by Nobel laureate David Baltimore -Based around m R N A production methods -Separates viruses into seven classes

RT- PCR is faster

•Virus identification: Nucleic acid analysis -Polymerase chain reaction (P C R) and reverse-transcriptase P C R (R T-P C R, see Toolbox 5.2) •Can be used to identify viruses by genome sequence •Can be used to study viral evolution patterns

How do viuses get their names be able to figure this out for an exam- why? because this literally were the labels from the petri dish of bacteria that they were isolated from. Mainly Rivers

•Virus names: -Historically, quite varied! •Simple letter/number combinations (T4 phage) •Organism(s) they infect (tobacco mosaic virus) •Location of discovery (Ebola River, Zaire) •Appearance (coronavirus, "crown") •Disease caused (hepatitis viruses) Historically, viruses have been named in a variety of ways. Many bacteriophages, such as T2 and λ, have been named with a combination of Roman or Greek letters and numbers. Some mammalian viruses have been named after specific locations. Other mammalian viruses, such as hepatitis A virus, have been named after the disease they cause. Most plant viruses, such as tobacco mosaic virus (see Figure 1.9D), have been named after the appearance of the infected plant. The names of other viruses are based on the shape of the virus.

Structure of viruses polio is one of the smallest viruses. Know based upon size compared to Pox viruses- what might this tell you about their genome? know that you have DS DNA, SS DNA, DR RNA, SS RNA FIGURE 5.3 Sizes and shapes of selected viruses Specific viruses differ in size. Picornaviruses, like poliovirus, are quite small. Poxviruses, like smallpox virus, are relatively large. Virus structures also differ significantly. The models depicted here represent average sizes and shapes. what does pico mean?

•Viruses are -Intracellular obligate parasites -Typically between 10 and 100 nm -Genomes of DNA or RNA are typically between a few thousand to 200,000 nucleotides in length Typically, the diameter of a viral particle is between 10 and 100 nanometers (1 nm = 10−9 meters, or one billionth of a meter!). Poliovirus, for example, has a diameter of approximately 30 nm, whereas the oval-shaped poxviruses like variola virus, the agent of smallpox, may be over 200 nm long. Bacteria and archaea, in contrast, typically have diameters from 1 to 10 micrometers (1 μm = 1,000 nm), and eukaryal cells generally have diameters from 10 to 100 μm (Figure 5.3). Not surprisingly, all viruses possess a genome, their genetic material. Even though all bacteria, archaea, and eukaryal organisms possess double-stranded DNA genomes, the genomic material of viruses may be DNA or RNA. Additionally, some viruses possess double-stranded genomes and other viruses possess single-stranded genomes. Some viruses possess circular genomes, while other viruses possess linear genomes. Most viruses possess a single genetic molecule, but a few viruses contain segmented genomes.