Intro to Virology
an infectious, obligate intracellular parasite comprising genetic material (RNA or DNA) surrounded by a protein coat and/or envelope derived from a host cell membrane
a Virus!!!!
Compare and Contrast Variolation and Vaccination
(which virus is used, who developed each method, what time periods were they used)
Variolation- smallpox (Variola virus); is possible for a human to die from variolation; developed in China around 1000BC; brought to Europe in 1721
Vaccination- cowpox (Vaccinia virus); less risks and SE than variolation; Edward Jenner is the father of vaccination; published findings in 1798
Define the following terms
Virion
Genome
Capsid
Nucleocapsid
Envelope
Virion- a complete, infectious virus particle (vs a DI particle)
Genome: DNA or RNA, but not both
Capsid: protein coat composed of multiple copies of a single (or a few different) capsomere proteins surrounding/coating the genome; called this when no membrane surrounds it
Nucleocapsid: capsid + genome; called this when they are covered by a lipid membrane (envelope)
Envelope*: lipid membrane surrounding capsid
* BONUS Q: where is the envelope derived from? Give 3 possibilities
What characterizes the Eclipse and Latent phases of viral replication?
Eclipse phase - virus is not detectable during this period
The virus completely disintegrates its viral structure so it can start replicating
Viral genome is released inside of host cell
Latent phase - virus is detectable inside the cell, but not outside of the cell (in the supernatant)
T/F When we say that a virus has evolved or adapted, we mean that an individual virion gets smarter and learns how to avoid detection by the immune system.
What kind of selection do viruses experience?
False. Virus evolution refers to a viral population and NOT the individual virion. Mutations are always happening, so there is genetic heterogeneity within the virus population. Due to selection pressure, certain mutants have more reproductive success.
Selection Pressure: Adapting to a new species of animal or avoiding detection by the immune system
Compare and Contrast a Naked virus to an Enveloped virus
Naked virus - nucleic acid with a protein coat (capsid)
Enveloped virus - nucleocapsid (nucleic acid with a capsid coat) surrounded by a lipid bilayer (called an envelope)
What contributions did the following people make in the history of virology?
Lady Montague
Onesimus
Edward Jenner
Lady Montague- witnessed variolation in Turkey; brought the practice to England in 1721
Onesimus- African slave brought to US; told his owner about tradition of variolation practiced in Africa; convinced Dr. Boylston to experiment with the procedure during the 1721 smallpox epidemic in Boston
Edward Jenner- used cowpox-infected scabs from milkmaids to experiment on/vaccinate children and then expose them to smallpox patients; published in 1798
What kind of viruses are susceptible to common detergents? What kind are much more stable and can persist in the environment for years?
Naked viruses are NOT inactivated by common detergents and are generally much more stable in the environment
BONUS Q: What types of disinfectant should you use to inactivate naked viruses and how long should you keep them in contact?
True or False- Adsorption is the first step in viral replication. In this step, extracellular viral particles exploit molecules on the surface of host cells for entry.
False. Adsorption IS the first step in viral replication, but it refers to viruses coming in contact with the cell, not entry. Entry is the second step of viral replication. During this step, viral ligands interact with receptors and co-receptors and enter via endocytosis or fusion with the plasma membrane.
Compare and Contrast :
drift vs shift
reassortment vs recombination (which one is more likely to cause a pandemic influenza virus)
drift = results in point mutations in the two major surface viral glycoproteins; H and N
shift = results in major genetic rearrangement (reassortment) of the H or N genes
reassortment = may happen when the cell is co-infected by two or more of the same segmented viruses (occurs between related viruses)
recombination = exchange of a portion of the genome between multiple genetically related viral genomes or host cell genetic material (ex. breaking and rejoining two DNA strains or when the polymerase changes or jumps from one RNA template to another RNA molecule during replication)
Give examples of how viruses are not always bad and how viruses were critical for the evolution of mammals
viruses are important for aquatic ecosystems (bacteriophages lyse bacteria and provide organic matter so that new aquatic life can be supported; about 1million viruses per 1mL of seawater)
clouds are seeded by viruses
5-8% of human genome is composed of endogenous retroviral DNA
viruses were critical for mammal placental evolution (retroviral syncytin genes allowed for placental formation to happen)
Which human virus and animal viruses were eradicated? How and when was eradication accomplished?
Smallpox was declared eradicated by WHO in 1979
The first virus we purposefully eliminated from the planet
Eradication program launched in 1967
Rinderpest virus (cattle plague) was eradicated in 2011
First eradicated animal disease
Use of modified live strain of Rinderpest virus in the Plowright vaccine made this possible
Very similar virus to human measles, paramyxovirus
Give examples of some small viruses and some large viruses.
Give examples of some viruses with a helical capsid, an icosahedral capsid, and a complex capsid.
Small virus examples: Parvovirus, Hepatitis, Papillomavirus
Large virus example: Ebolavirus, Variola Virus, Herpesvirus
Helical: -ssRNA viruses
Simple Icosahedral: small viruses (Poliovirus)
Complex Icosahedral: (ex. Adenovirus)
Complex (not entirely helical or icosahedral in symmetry; pleomorphic [odd or not uniform in shape]): large viruses (ex. Poxviridae family)
Describe the two major mechanisms that viruses use to enter host cells
(1) Endocytosis is receptor-mediated. The virus binds to a ligand on the host cell surface and is then pulled into the cell coated in an endosome.
(2) Non-endocytic route of entry- the virus fuses with the cell membrane and is brought into the cell UNcoated
Stable, Evolving, Dead-end, and Resistant host describe different types of interactions of hosts and viruses. What does each refer to?
Stable- virus is maintained in the ecosystem
Evolving- passage of a virus from "experienced populations" to naive populations in the same host species (human flu)
Dead-end- a one-way passage into a different species. Either the host dies or the virus does not transmit efficiently in the new species (ex. WNV)
Resistant host- some host species is not susceptible to infection by that virus (ex. CPV-2, FeLV or Shope's papillomavirus)
Compare and Contrast how viruses are different from bacteria and other microorganisms
Viruses are much smaller than bacteria
viruses replicate exponentially rather than by binary fission
viruses can't synthesize their own proteins, ATP,
viruses can't be cultured on artificial medium like bacteria can
viruses aren't susceptible to antibiotics the way some bacteria are
What contributions did the following people make in the history of virology?
Loeffler and Frosch (1898)
Walter Reed (1901)
Ellerman/Bang/Rous (1908-1918)
Richard Shope (1931)
Loeffler and Frosch- first animal virus : foot-and-mouth disease in cattle
Walter Reed- discovered yellow fever virus; first virus affecting humans
Ellerman/Bang/Rous- discovered that cancerous tumors in chickens were caused by viruses (Avian leukosis virus and Rous sarcoma virus)
Shope and Rous - Shope’s papillomavirus in rabbits
Richard Shope- (1931) isolated and identified the first influenza virus, swine influenza virus from pigs
Know how viruses are classified (e.g. basis of the Baltimore system). What does + and - sense mean?
Unlike bacteria and fungi, most viruses are called by their species classification
Baltimore Classification
The relation of the viral genome to the sense of mRNA
Genome: DNA or RNA?
Single or double stranded?
If ssRNA: positive or negative sense?
+ssRNA: an RNA that can interact with a ribosome and cause proteins to be made
mRNA is designated as positive (+) sense
-ssRNA: an RNA that can’t interact with the ribosome to cause proteins to be made
The method of replication follows
RNA viruses typically uncoat at the ___ in order to replicate in the _____
DNA viruses typically uncoat at the ___ in order to replicate in the _____
*What are some exceptions?
plasma membrane (or within an endosome); cytoplasm
nuclear membrane; nucleus
Exceptions:
Retroviruses (RNA) and Influenza (RNA)- replicate in the nucleus
Poxviridae (DNA) and Asfarviridae (DNA) families - replicate in cytoplasm
What is reversion of virulence and how might a virus (vaccine particle) revert to virulence?
What is viral reactivation?
Reversion of Virulence - a concern with a modified live virus (MLV) vaccine, that it may replace the missing genes and genetically recombine with the wild type virus to again become virulent
Overcome this concern by deleting multiply virulence genes instead of just a single virulence gene
Viral Reactivation - may occur when multiple inactivated (killed) viral particles can recombine genetic material to produce an infectious virion -- more theoretical than realistic, but still possible
Nipah virus
1. what type of virus is it?
2. who was affected in the 1998 outbreak?
3. how was the virus spread?
4. how was the virus contained?
1. Group V Paramyxovirus: -ssRNA coated in Nucleoportien (N)
2. pigs and farmers in Malaysia
3. bats are the natural reservoir host- many frugivorous bat species fed in the orchard that were interspersed among the pig farms
4. movement ban and culling 1.1 million pigs (40% swine population)
In 2003, a pox-like outbreak in the mid-western USA, affected 71 humans who had previous contact with pet prairie dogs. What was the cause of the outbreak traced back to? (natural host, virus identified, virus characteristics)
The distributor had housed the pet prairie dogs with Gambian rats, the natural host of Monkeypox virus (Poxviridae family).
Poxvirus has a large linear dsDNA genome (Group 1) with an enveloped nucleocapsid. Unlike most DNA viruses, poxviruses replicate in the cytoplasm.
The smallpox vaccination prevents monkeypox disease.
African swine fever virus is the only member of the virus family Asfarviridae. Who did this outbreak affect and where? What are some other characteristics of this virus and how was the outbreak contained?
In China, domesticated swine herds contracted African swine fever (highly virulent ~100% death of infected pigs) from wild boar
large dsDNA genome (group 1); replicates in cytoplasm similar to Poxivruses; virus particle contains RNA polymerase
No vaccine
pigs were culled
Summarize how influenza A and adenovirus/parvovirus particles enter a host cell, uncoat their genome, and enter the nucleus.
Influenza A- enters cells via endocytosis (viral HA binds to cell surface sialic acid-GP). Envelope fuses with endosome membrane and virus uncoats (nucleocapsid is released into cytoplasm). Nucleocapsid covered RNAs are small enough to enter nucleus through nuclear pore
Adenovirus- capsid disassembles at nuclear pore, genome enters nucleus
Parvovirus- virion enters host cells by CME, escape from endosome into cytoplasm, the virion is small enough to translocate through nuclear pore and enters the nucleus where it uncoats its DNA genome
Which viruses were released into the wild to control the invasive rabbit population in Australia?
Poxvirus- which causes myxomatosis in rabbits; released into wild in 1950
Rabbit calicivirus (rabbit hemorrhagic disease) was similarly released in the 1990s
resistance is once again developing