Microbiology Chapter 6: Viruses and Prions

Tamiflu

A drug that is also called oseltamivir. Prevents influenza A and influenza B virions from budding off the host cell surface. Blocks release of virions from the host cell.

Postexposure Prophylaxis

A prevention treatment applied after an exposure to limit infection. Example: A lab-prepared mixture of injectable antibodies to the rabies virus prevents the virus from binding to and entering host cells. Administered if a rabid animal bites a person who has not been vaccinated against rabies. Blocking viral penetration is a key strategy in ____ against HIV. The injected peptide drug enfuvirtide is administered to people who suspect they have been exposed to HIV, such as a health care worker who gets an accidental needle stick while caring for an AIDS patient. The drug binds to proteins essential for HIV to enter new cells. It works by blocking fusion of the viral envelope with host cell membranes.

Virion

A single, infectious virus particle. All have an exterior protective protein capsid, packed with genetic material (DNA or RNA).

ssRNA+

A single-stranded RNA genome may be in a form that can be directly translated by the host cell ribosomes in the cytoplasm. The RNA genome functions as an mRNA. These include causative agents of polio, rubella, West Nile encephalitis, and dengue fever.

Oncogenic Viruses

Also called oncoviruses, Viruses that cause persistent infections that can cause cancer. Include DNA and RNA viruses. Some integrate into the host genome, while others are maintained episomally - or separate from the host chromosome and maintained either in the nucleus or cytoplasm. Cause between 10-15% of cancers. These increase risk for cancer, but do not guarantee cancer will develop. Cause cancer by stimulating uncontrolled host cell division, and/or decreasing host cell responsiveness to death signals. Example: Human papillomaviruses (HPVs). There are more than 200 different types of HPVs, at least 40 of which spread through sexual contact. About a dozen types have been linked to cancer, with HPV-16 and HPV-18 causing the majority of cases. Even the HPV viruses most associated with cancer are usually cleared up by the immune system within 1 or 2 years without further problems. About 90% of cervical cancer cases are linked to the virus. Due to this, all children 11-12 years old should get the Gardasil vaccine that protects against HPV types that are most frequently associated with cancer. Example: Human T-lymphotropic viruses (HTLV). HTLV-1 and HTLV-2 are clinically important. These retroviruses form a provirus and can quickly persist in host cells for more than a decade before emerging to cause leukemia or lymphoma. Approximately 20 million people are infected with these viruses worldwide. Primary modes of transmission are through sexual contact, blood contact, and breast milk.

Antisense Antivirals

Can block viral replication. Agents are short sequences of nucleotides that are complementary to the RNA transcribed by specific viruses. Can bind to viral mRNA, preventing the host ribosome from translating the viral mRNA. Targeted RNA is destroyed by cellular enzymes. Only one approved drug to treat viral associated pathologies is vitravene. This drug has been replaced by safer and more effective therapies; no longer manufactured.

Immortal Cells

Cells that ignore death signals. May undergo repeated division and survive indefinitely.

Host Range

Collection of species that a virus can infect. Some viruses infect more than one species, while other infect only infect one species. Example: measles virus is only able to infect humans. Most viruses than can infect human can infect other animals. Most human viruses evolved in other species and then through genetic changes they gained the capacity to infect us. For example: the avian influenza (bird flu or H5N1), which primarily infected geese and ducks, underwent genetic reassortment that expanded its _____ to now include humans. The same holds true for swine flu, which initially infected pigs and can now infect humans.

Obligate Intracellular Pathogens

Disease-causing microbes that must invade living cells and hijack their biochemical and cellular tools to replicate. These are known as viruses. This is why viruses are considered nonliving.

Antigenic Shift

Drastic changes to the HA and NA spikes due to a major genetic reassortment by influenza viruses. Broader mutations that often lead to viral strains with new features, such as increased infectivity or expanded host range. This is what occurred when the avian and swine influenza strains "jumped species", becoming able to infect humans. Vaccines are unlikely to exist for this new virus. People will have no residual immune protection from prior influenza infections or vaccinations. These set the stage for a worldwide outbreak or pandemic. Because of the limited pre-existing immunity in the population, pandemics may have a dramatically increased mortality rate compared with epidemics caused by the earlier, progenitor virus strains.

ssRNA-

Encompasses a wide variety of pathogens, including the causative agents of influenza, measles, ebola, and rabies. Have an RNA genome that is complementary to mRNA. Their RNA genome must be transcribed into a readable mRNA format before translation, accomplished by virally encoded enzymes called RNA-depended RNA polymerases (RdRPs) that build new RNA from an existing RNA template.

Reassortment

Events that contribute to viral evolution. May occur when 2 different viral strains co-infect a single host cell, and their genomes can mix and generate new viral strains, or a virus with a new genetic combination. Effects in viral evolution are modeled in influenza viruses.

Provirus

Formed by viruses that cause persistent infection integrating their genome into the host genome. It is transcribed to make the viral genome and translated to make viral proteins. Resemble the prophage made by temperate bacteriophages. They do not excise themselves from the genome to employ the "abandon ship" approach seen in lysogenic bacteriophages. Retroviruses like HIV are notorious for forming a ____ in infected cells and then remaining silent for years before releasing sufficient virions to destroy the host's immune system. Papillomaviruses, which are best known for causing cervical cancer, form ____ and generate persistent infections.

Prophage

Formed when the bacteriophage genome integrated itself into the host genome in the lysogenic replication pathway of temperate phages. Medically important due to their ability to confer new pathogenic properties to bacterial cells, a situation called phage conversion. Phage conversion provides new pathogenicity factors to a bacterium, such as the capacity to make certain toxins. Example: the bacterium that cause diphtheria, Corynebacterium diphtheria, gained its ability to make the potent diphtheria toxin from a ____. Example: The botulinum toxin made by the bacterium that causes botulism, Clostridium botulinum, is encoded by a ____. Exhibits an "abandon ship" approach when the host cell carrying a ____ is stressed and will excise itself from the host genome and enter the lytic replication pathway.

Antiviral Drugs

In most cases, only limit infections rather than cure them. Because viruses are not cells, they cannot be eliminated through typical drug actions that affect bacterial, fungal, or protist pathogens. Any step in viral replication pathway is a potential drug target. Basic research into how a given virus gain entry into a host cell and then replicates is essential to developing ___. To be an effective drug rather than just a poison, ____ should be selectively toxic, stopping the pathogen but leaving the host cells unharmed. Viral pathogens exist inside host cells, so drugs cannot always reach them. Drug targets processes unique to the pathogen- but this is hard to achieve when viruses use the host cell's own machinery and metabolism. A number of ____ prevent viral entry into cells by blocking attachment or penetration.

Capsomeres

Individual 3D subunits that make up capsid shape based on their arrangement. These build capsids. May be made from a single type of protein or a collection of different proteins. Good place for antiviral targets.

Productive Infection

Infections in which A virus infects a host cell and immediately starts making new virions.

Chronic Infections

Infections that are characterized by the continuous release of virions over time and a slow progression of disease. In some cases, a period of quiet infection for months or years precedes a period of active viral replication. In the quiet period, host cells produce a small number of virions. The disease is not evident, but the patient can still pass the virus to others. Exhibit steady viral production that may increase over time. Example: Human immunodeficiency virus (HIV), which impacts the immune system by killing T-cells, follows this slow progressing ___ model. If infected in the quiet stage, patients are said to be "HIV positive". Without treatment, the quiet stage eventually ends. Virus count increases and healthy T-levels drop, causing loss of immune function. The end stage of HIV infection is called acquired immune deficiency syndrome, or AIDS.

Persistent Infection

Infections that tend to remain in the host for long periods of time- from many weeks to a lifetime. Caused by viruses that have different replication strategies that allow them to avoid immune system clearance. Most ____ are chronic (HIV) or latent.

Prions

Infectious proteins. Nonliving and acellular. Do not have genetic material and do not replicate. Cause a class of diseases called transmissible spongiform encephalopathies (TSEs), which destroy brain tissue. A normal ___ is found throughout the nervous system, but is especially prevalent in the brain. Have a neuroprotective role. When these are misfolded, they cause serious damage to the nervous system. As misfolded ___ clump together, brain tissue deteriorates, and spongy holes are left in the brain. ___ infect nervous tissues and cause sponge-like holes in the brain.

Rabies

Known as HRIG, human rabies immunoglobulin. Vaccine preventable, but the vaccine is not routinely used in humans unless they are at increased risk for exposure, such as vets or people that research ____. Even if ____ vaccine was administered immediately upon exposure to a rabid animal, it takes weeks before the patient makes sufficient antibodies to protect from infection. Having a viral attachment blocker is an important part of the medical toolkit against ____, since there have only been a handful of people who have survived the full-blown infection. Postexposure prophylaxis is used to treat ____; a lab-prepared mixture of injectable antibodies to the _____ virus prevents the virus from binding to and entering host cells.

Viral Envelope

Lipid-based structure that surrounds the capsid of a virion. Seen in some animal viruses. _____ viruses develop by budding from the host, and taking a portion of the cell membrane with them as a coating when they go.

Antigenic Drift

Minor changes to the HA and NA spikes due to influenza's RNA genome mutating frequently. These minor changes allow the virus to evade a quick antibody response by making the new strain different enough to go unrecognized by the immune system, even if the host had a prior interaction with a related strain. This is the reason we need a new a different flu shot every year. There is always a portion of the population susceptible to the latest virus, which in turn leads to a seasonal outbreak. Minor virus changes may greatly impact public health, as they allow viruses to thwart the "memory" mechanism of our immune response.

Viral Genome

Most viruses have less than 300 genes. The smallest viruses have less than 2,000 base pairs in their whole genome (which is much smaller than the genomes in eukaryotic and prokaryotic cells). ____ can be RNA or DNA, and the nucleic acid present can either be single or double stranded. Can exist in diverse arrangements. May spread over multiple segmented sections, or it could be a single circular or linear molecule. The virus must use its ____ to direct the production of mRNAs that the host cell then translates into proteins. Can be either RNA or DNA, single or double stranded, single or segmented sections, and circular or linear. The DNA ____ are circular or linear, often double stranded, and may also be single stranded. The RNA ____ are linear or segmented, often single stranded, and may also be double stranded. Exhibit a faster rate of genomic change than living infectious agents because of their quick replication time and large quantity of virions released within a host.

RNA Genome

Mutate more and evolve faster than their DNA counterparts because RNA polymerases, which copy RNA, do not have proofreading capabilities like DNA polymerases. DNA viruses may mutate once per thousand rounds of genome copying, while RNA viruses may mutate once every round of genome copying.

Interferons

Naturally occurring substances released by cells in response to viral infections. Signal the presence of a virus, causing neighboring, uneffected cells to make defensive changes that limit viral entry and/or replication. Can be produced in the lab and administered to help limit the progression of certain viral infections. Therapies have been used to treat hepatitis B and C infections in combination with other drugs. Tend to generate flu-like symptoms as side effects, making them a fairly unpleasant treatment option.

Viral Spikes

Or peplomers, that may protrude from the viral capsid, or if present, from the viral envelope. These are glycoprotein extensions that help viruses attach and gain entry into host cells. Have an important role in determining what species and tissues the virus can infect because they can only bind to specific factors on a given host cell. If the host develops an immune response to the ____, and the ___ then change (something that certain viruses do rapidly and routinely in their genetic evolution), then the new virus may escape immune detection with the changed _____. Also serve as antigens against which the immune system creates specific antibodies. Example: influenza viruses frequently mutate and experience small changes in ___ proteins. Influenza's hemagglutinin (HA) and neuraminidase (NA) _____ affect how these viruses interact with host cells and how the host's immune system recognizes these viruses. There are at least 18 known variations of HA ____ and 11 characterized variations of NA glycoproteins in influenza A.

Bacteriophages

Or phages, are viruses that only infect bacteria. Exhibit a complex capsid structure. Usually have capsids with icosahedral symmetry. Often, their capsids are associated with additional complex structures that enable them to inject their genome into target cells. They are always naked (nonenveloped) viruses because they lyse (or burst) host cells. Do not infect human cells. Medically important because they serve as a means for bacteria to evolve. ___ facilitate specialized and generalized transduction, which allow bacteria to develop new genetic combinations despite their inability to sexually reproduce. These are diverse and use different mechanism for host cell infection and subsequent, viral replication. Some, like the T-even ___, infect the host bacterial cell and immediately build new virions.

Lysogenic Replication

Replication pathway that is used by bacteriophages such as lamba phages that are called temperate phages. The first 2 steps, attachment and penetration, are the same as in the lytic replication pathway. Following the penetration step, the phage genome is incorporated into the host cell genome, forming a prophage. As the infected bacterial cell divides, it copies its own genome as well as the prophage's genome. Therefore, a single infection event ultimately results in many cells carrying the bacteriophages genome. If a host cell carrying the prophage is stressed, the prophage may excise itself from the host genome and enter the lytic replication pathway. This "abandon ship" approach allows the bacteriophage to replicate and find a new host before its current host cell dies.

Animal Virus Replication

Replication that had 6 main steps: 1. Attachment: naked viruses attach to host cell membranes through capsid proteins. Other viruses (both naked and enveloped) use spikes. Viral envelope or capsid proteins attach to host cell plasma membrane proteins to facilitate attachment. Specificity of this binding is why viruses exhibit host range and tissue tropism. This makes attachment proteins a target for drug therapy to limit or prevent infection. One drug called maraviroc works by blocking HIV's attachment to host cell proteins. 2. Penetration: Enveloped animal viruses enter the host cell through endocytosis or membrane fusion. Naked viruses mainly enter by endocytosis. 3. Uncoating: Animal virus capsids enter the host cells. The capsid is entirely or partially broken down, releasing the viral genome. A virus that entered by endocytosis usually has its capsid digested away by enzymes in the endocytic vesicle. Viruses entering by membrane fusion may have their capsid degraded by enzymes in the host cell cytoplasm. 4. Replication: The viral genome is replicated and viral proteins are made. 5. Assembly: New virions are assembled. The capsid assembles around the genome. 6. Release: Newly assembled enveloped viruses are released by budding off the host cell. Viral envelope proteins must be embedded in the host cell plasma membrane before the budding occurs so the enveloped viruses take a portion of the cell's plasma membrane. Naked viruses rupture the host cell during release, usually killing the cells.

Icsahedral Capsids

Structure that surrounds the genome of a virion. Looks like 3D polygons, but may appear fairly spherical. Ex: a soccer ball is spherical, yet made of multiple hexagon and pentagon shapes.

Virology

Study of viruses. Essential for any health care provider.

Virus

Submicroscopic, Infectious, nonliving agent that is invisible when viewed through a light microscope. Describes as filterable infectious agents, reflecting their tiny size compared with cells. Over 5,000 mammal-infecting ____ species have been described. Of these, at least 220 infect humans. At least 320,000 mammalian viruses remain uncharacterized. About 70% of _____ that infect humans tend to be harbored in other animals. Extremely small size (20-400 nm). Structural and genomic features of a ___ dictate what sort of host the ___ can infect, as well as the progression of the infection. ___ are not cells, hence they are called acellular and considered nonliving. One reason ____ are considered nonliving is because they are incapable of synthesizing their own components, such as nucleic acids or proteins, without the help of the host cells they infect. As such, they are called obligate intracellular pathogens, or disease-causing microbes that must invade living cells and hijack their biochemical and cellular tools to replicate. They also lack the metabolic processes to extract energy from nutrients. Genome is DNA or RNA. Their structure is a protein capsid coating and nucleic acid. Can infect every branch in the tree of life. Most have less than 300 genes because since they do not have to build organelles and they do not have metabolic processes to mediate, they do not require many genes to exist. The goal of all ____ is to get a host cell to make viral proteins, so more virions can be built. Once inside the host cell, it commandeers the host cell's energy, enzymes, organelles, and molecular building blocks such as amino acids to build new virions.

Seroconversion Window

Th time period between infection and development of detectable antibodies. At least a couple weeks following infection. Example: For HIV, the _____ can be several weeks to months. This makes methods that detect patient antibodies against HIV an unreliable tool to assess infection status. For this reason, it is helpful to use a combination of detection methods.

dsRNA

The double-stranded RNA genome is transcribed to make mRNA. Then the RNA has to be unwound, so that RNA polymerases can transcribe it into an mRNA format. Virally encoded RNA-dependent RNA polymerases are required. Example: rotaviruses, which cause severe diarrhea, are ___ viruses.

Nucleoside Analogs

The most common drugs that block viral replication. They all work by blocking successful nucleic acid production to limit viral replication. In certain virus-infected cells, they are activated into compounds that mimic normal nucleotides (A, G, C, T, and U). They are chemically different from natural or normal nucleotides and represent a chemical dead end for nucleic acid replication. If DNA or RNA polymerase uses the ____ instead of a normal nucleotide, nucleic acid replication will be blocked. At least a dozen drugs in this class. Example: acyclovir (active ingredient in antiviral drugs Zovirax and Valtrex), is one of the best known ____and targets DNA-based viruses. It blocks DNA replication in cells infected with HHV-1, HHV-2, or HHV-3. Only cells with these HHV viruses can chemically modify the drug to activate it. The activated drug mimics guanosine (G) nucleotides that DNA polymerases use to make DNA. If it is incorporated, it prematurely ends DNA replication. Example: Ribavirin is a ____ that targets RNA polymerases and is used to combat RNA viruses. Mostly effective against human respiratory syncytial virus and hepatitis C; and also may have efficacy in early infections with Lassavirus, hantavirus, and some others that cause hemorrhagic fevers (but not Ebola).

Capsid

The protein shell that packages and protects the genome and also accounts for the bulk of a virion's mass. The shape is based on how the individual 3D subunits, called capsomeres, are arranged. _____ of most animal viruses have helical or icsahedral symmetry. These often exhibit self-assembly, meaning that the amino acid sequence determines how the final proteins fold and come together to make the larger ___ structure. More complex viruses use host cell machinery to put __ together properly. Assembly is a central part to virion formation, therefore it represents a potential target for antiviral drugs. Made of capsomere subunits.

Episomally

The viruses genome remains outside the host's genome. Example: viruses that cause latent infections such as the Herpesviridae family.

Virus Names

These ___ reflect virus size, host range, tropism, and disease features because they help to refine the grouping of viruses into species. Viruses are groped by the following properites: 1. Type of nucleic acid present (RNA or DNA). 2. Capsid Symmetry (helical, icsahedral, or complex). 3. Presence or absence of an envelope. 4. Genome architecture (ssDNA, ssRNA, etc.).

Viral Genes

These genes encode capsomere proteins, enzymes needs for viral replication, and structural factors.

Latent Infections

These infections are distinguished by flare-ups with intermittent periods of dormancy (latency). During the flare-up, virions are shed and the infected person experiences symptoms. Flare-ups can be triggered by any stress to the host, including an infection with another pathogen, fever, sunburn, hormone level changes, and immune suppression. When flare-up is over, the virus retreats into a period of inactivity, during which virion levels fall drastically and may be difficult to detect. Example: Members of the Herpesviridae family are notorious for causing ____ by going dormant in certain host cells. They do not integrate into the host genome; instead, they exist episomally, or their genome remains outside the host's genome. Human Herpes virus-1 lies dormant in host nerve cells and then reemerge to generate cold sores. HHV-2, which causes genital herpes, follows a similar pattern of latency and active replication. Varicallea-zoster virus (HHV-3) that causes chickenpox, persists episonally in host nerve cells and reemerges to cause shingles. Intermittent flare-ups and retreats make it hard for the immune system to eliminate the virus. Episodic bursts of virions that allow for transmission to the next host.

Acute Infection

These infections run their course and are cleared by the host immune system. Nonpersistent. Viruses that employ the normal mode of animal virus replication cause these infections. Ex: common cold and influenza. Viral replication peaks, followed by immune clearance of the virus.

Lytic Replication Pathway

This replication pathway kills the host cell as newly made bacteriophages are released. Used by T-even bacteriophages. Infect the host bacterial cell, immediately build new virions, and kills the host cells as newly made bacteriophages are released. Involves 5 key steps: 1. Attachment (adsorption): The bacteriophage binds to the bacterial cell. Come together from random contact. 2. Penetration (entry): bacteriophage injects genetic material into the cell, through the host's cell wall and plasma membrane. The empty capsid remains outside of the host cell. 3. Replication (synthesis): Once the viral genome is inside the host cell, the bacterophage commandeers the host cell factors to transcribe and translate viral genes. The viral genome is then replicated. The host cell DNA is broken down by the bacteriophage DNAases. 4. Assembly (maturation): Once all of the parts of the bacteriophage are replicated, viral factors pack the viral genome into the capsid and the remaining phage parts are assembled. Hundreds to thousands of new bacteriophages are generated in this step. 5. Release: Bacteriophages encode an enzyme called lysozyme, which breaks down host cell walls and causes bacterial cell lysis (bursting) once the newly assemble phages are mature. The released bacteriophages can then infect other cells.

Bacteriophage Replication

Use the Lytic replication pathway (some, like the T-even bacteriophages). This means that once they infect the host bacterial cell, they direct replication and kill the host cell.

Naked

Virions that lack an envelope (nonenveloped). ____ viruses lyse (burst) out of a host cell and do not coat themselves in an envelope. All bacteriophages lyse host cells, so these complex-shaped viruses are therefore always ___.

Tropism

Viruses exhibit specificity regarding what tissues or cells they will infect in their given host. Due to virus surface factors only being able to bind to specific surface molecules on certain host cells.

Broad Tropism

Viruses that can infect a wide range of host cells or tissues. Example: Ebola.

Animal viruses

Viruses that infect animals and humans. Some have a lipid envelope around the capsid. May be enveloped or naked. Naked _____ (and sometimes enveloped ___) enter the host cell through endocytosis, which is viral binding to the host cell surface receptors that triggers an uptake of the virus into vesicles. Enveloped ____ with spikes enter the host cell through membrane fusion, in which the host cell's plasma membrane and the viral envelope blend together, releasing the viral capsid into the cytoplasm of the host cell.

Narrow Tropism

Viruses that may specifically target only one type of cell or tissue in the given host. Example: the hepatitis viruses target the liver, so they are described as hepatotropic (hepato means liver). Example: Human T-lymphotropic viruses get their name as a result of their partiality for infecting human T-cells, which are specialized white blood cells, of the immune system. This virus name reveals the virus's _____ tropism and host range.

Complex Structure

Viruses with less conventional capsids. Some animal viruses, such as the Poxviridae family that includes the small pox virus, have ovoid or brick-shaped capsids. Bacteriophages often have capsids with icsahedral symmetry, but their capsids are associated with additional ____ that enable them to act like hyodermic syringes that inject the viral genome into target bacterial cells. Deviations from the structures of helical capsids and icsahedral capsids.

Helical Capsids

structure that surrounds the genome of a virion. Looks like a hollow tube.