Module 4 Flashcards
Briefly describe the nature of viruses.
Viruses are obligate intracellular parasites.
Can the extracellular forms of viruses repair themselves?
No. The extracellular forms can’t undergo repair because they are metabolically inert.
What makes viruses unlike cellular life forms?
Virus genomes can be made of either DNA or RNA, however no singular virus has both RNA genomic material and DNA genomic material in its capsid at the same time
The extracellular for is metabolically inert, only the intracellular form is metabolically active, and even then it’s situational
They cannot repair their extracellular forms
Where are you more likely to find an envelope virus: amongst animal viroids, or bacterial viroids?
Animal viroids
How do enveloped viruses mediate adhesion and membrane fusion to their target cells?
Their envelopes are usually studded with glycoproteins, which mediate adhesion and membrane fusion with the target cell.
Describe the double duty positive sense single stranded RNA genomes pull.
They are basically mRNA in addition to being the genome. They are used to make a negative sense copy of the genome in addition to coding for proteins.
What do all RNA viruses, aside from retroviruses, require in order to replicate?
Viral replicase, an RNA-dependent RNAP (RDRP)
How do RNA viruses make a positive sense copy upon entry to start replication if there’s no viral replicase to be found in the host?
They bring the viral replicase with them pre-formed.
What is the function of an interferon to the host cell?
It calls out to other cells to alert them that a viral infection is lurking.
True or false: Intramuscularly injected vaccines are great at stimulating circulating IgG and at producing mucosal antibodies.
False. They’re great at producing IgG antibodies, but not for mucosal antibodies.
How do viruses spread from one species to another?
The virus must undergo either antigenic shift, antigenic drift, or reassortment.
What is antigenic shift?
The rapid alteration in genotype and phenotype of a virus due to the acquisition of a different RNA segment. This is faster than antigenic drift and is the cause of most major influenza variants.
What is antigenic drift?
Mutations in the viral genome caused by RDRPs low fidelity rate (aka high viral mutation rate). This is slower than antigenic shift.
What is reassortment as it relates to viral genomes?
Simultaneous infection of two types of viruses in one host, leading to fragments of both viral genomes being combined into the capsids, creating a new virus. New HA and NA segments can cause especially severe pandemics because no one’s been exposed to the new proteins before, no immunity has been built up.
Why do viruses typically shut down the host translational machinery? What benefit do they gain from this?
Shutting down the host translational machinery shuts off host gene expression, which prevents the host from responding to the viral infection or from sending out an interferon to alert neighboring cells of the lurking virus.
Additionally, this global inhibition of host protein synthesis ensures maximal viral gene expression.
In addition to processing viral proteins, what other functions do viral proteases have?
They’re important for virulence as they stop the host from producing their own proteins, culling any response to the infection (like synthesis of an interferon) and allowing all of the host’s resources to go into viral replication.
Definition of the latent period:
No phages observed extracellularly
Definition of the eclipse period:
No phages seen either extracellularly or intracellularly
Definition of bust size:
A virus-specific measure of how many viruses can be produced from one bacterial cell.
How do T4 and T7 bacteriophages infect E. coli?
They randomly land and attack with their tail fibers (note that all 6 tail fibers must be engaged to initiate infection) to either the LPS core polysaccharide (the least variable portion of the LPS) or to certain strains of OmpC. Binding triggers a protein chain that drives the contractile sheath to push the genome into the cell. These bacteriophages also use lysozyme to penetrate/degrade the peptidoglycan.
What is a prophage?
A virus that incorporates its DNA into the bacterial genome.
What is a lysogen?
A bacterial strain with a prophage in its genome.
What’s the difference between a prophage and a lysogen?
A prophage refers to the viral DNA in a host bacterium’s genome. A lysogen refers to the bacterium that has the prophage in its genome.
True or false: Under most circumstances, most prophage genes are expressed in a lysogen.
False! Under most circumstances, most prophage genes are NOT expressed in a lysogen!
What causes cell death in a viral infection?
Viral gene expression (NOT presence or replication of a viral genome!)
How is a prophage maintained in a lysogen?
By using a viral repressor protein to minimize viral gene expression.
What happens if a lambda lysogen loses its ability to produce the C1 protein?
It will lose control of viral gene expression and the lytic phase will begin.
What is the signal that causes the lambda virus to be resurrected from the host genome and why?
The presence of LexA. It signals that the cell has activated its SOS response and things are going downhill, so it’s time to get out of the host genome and replicate before the host dies.
Lambda virus’s C1 repressor protein has structural and sequence similarity to what bacterial protein?
LexA
What is the effect of DNA damage on RecA?
It stimulates RecA to cleave both LexA and C1
What is the effect of C1 cleavage by RecA?
It releases transcriptional repression on all lambda genes, including Xis → excisionase
What is the function of excisionase in lambda’s viral infection?
Excisionase cuts the prophage out of the E. coli chromosome for circularization.
How is lambda’s prophage genome removed from the host genome?
Excisionase cuts it out
Why, under normal conditions, don’t infectious virions result in the lysis of other cells in a population of lysogens (this population is made up of lysogens of the same virus)?
Immunity. Lysogens are immune to superinfection by the same virus. This is due to the prophage-encoded repressor protein. C1 represses expression of other viral genes, maintaining lysogeny, and it also represses gene expression from the same incoming virus. A lysogen can be killed by other viruses, but not by the one already contained in its genome.
True or false: a lysogen can be killed during a superinfection with the same virus.
False
What mediates the “decision” to progress with lysogeny?
Poor nutrition, because without sufficient energy or resources, synthesis of new viruses is difficult.
Why do high Multiplicities of Infection (MOIs) favor lysogeny of lysis?
Because if a viral population greatly outnumbers the host cell population, the entire host pop. may be killed, forcing the virus to exist free in the environment where it’s vulnerable for longer.
What are restriction endonucleases?
Enzymes that bacteria have evolved to degrade foreign DNA. They cut DNA at specific sequences.
One famous example is TaqPolymerase, used in PCR
What is the Restriction-Modification system and what does it do?
For each restriction endonuclease, there is a cognate DNA methylase that recognizes the same palindrome and adds a methyl group to one nucleotide on each strand. This serves to protect the bacterium’s own DNA. By methylating its inverted repeats that its restriction endonucleases bind to, it prevents binding and subsequent destruction
What is the purpose of a toxin-antitoxin module?
To defend against viral infections and to protect the bacterial population.
How does a toxin-antitoxin module work?
During a viral infection, the virus stops normal host processes, like transcription and translation. In doing so, the host stops producing its toxin and antitoxin molecules. Because the antitoxin molecule is designed to have a shorter half life than the toxin and will subsequently degrade first, the toxin left behind kills the host, preventing the virus infecting it from replicating and releasing 100s of more baby viruses into the surrounding population. It’s almost a form of altruistic apoptosis.
What does CRISPR stand for?
Clustered regularly interspaced palindromic repeats.
What kind of genome do picornaviruses have?
Positive sense ssRNA
What are some examples of picornaviruses?
Hepatitis A, Hand+Foot+Mouth disease, polio, rhinoviruses.
What kind of genome does polio have?
Positive sense ssRNA
Polio can potentially be driven to extinction, although this hasn’t happened yet. What will allow us to one day make it extinct?
Polio has no animal reservoir, and thus nowhere else to hide except for in humans. This is pretty common amongst viruses, as most are specific for only certain tissues in certain species because of the presence or absence of appropriate host receptor molecules.
What host receptor protein does polio use and where are these receptors found?
Uses CD155 (aka necl5), found only on human enterocytes, pharyngeal cells, and the anterior horn of the spinal cord.
Why is polio technically not a central nervous system virus?
It’s not a central nervous system virus because it evolved for our intestinal tract. Entering the CNS is a dead end for them, it’s an accidental infection (GI infections are easy to spread from human to human, CNS infections not so much).
What’s the difference between the virus in the Salk vaccine vs the virus in the Sabin vaccine?
Salk → inactivated virus. Induced predominantly IgG antibodies, gave humoral immunity. Protected from disease, not infection.
Sabin → attenuated virus. Induced serum IgG and mucosal IgA antibodies, gave total immunity from infection, not just the disease
Why did poliomyelitis only become an epidemic disease in the 20th century, and why did it, a fecal contaminating virus, only proliferate in countries with high hygienic standards?
In areas where infants are more likely to be infected soon after birth, polio epidemics didn’t occur because most of the children are protected due to having passive immunity (from their moms) at the time of infection. The moms had antibodies for polio infections, and their passive immunity is still present in their infants very early in their life.
Why is polio an important virus to understand?
Because it represents a large subgroup of the picornaviruses, which are themselves a subgroup of enteroviruses. Also, viruses that infect the enteric (intestinal) tract occasionally can get out and infect other parts of the body (secondary viremia tissue)
What is humoral immunity?
Immunity mediated by antibodies circulating in bodily fluids
Which kind of antibodies did the Salk vaccine induce? What is the significance of this?
Predominantly IgG antibodies. This gave protection from the poliomyelitis disease, but not from poliomyelitis infection. It gave humoral immunity, not intestinal/mucosal immunity.
Which kind of antibodies did the Sabin vaccine induce? What is the significance of this?
Induces serum IgG and mucosal IgA antibodies.
Prevents poliomyelitis infection, not just poliomyelitis disease.
Why would a patient develop paralytic poliomyelitis after taking the Sabin vaccine?
The attenuated virus in the vaccine lost the mutation and became lethal again. The virus reverted to neurovirulence.
Describe the structure of the polio virus
Naked virus, no envelope. Capsid is geometric, isohedral with 20 faces, and is made of 3 proteins (VP1, VP2, VP3). VP4 lines the inner portion of the capsid. Inside, its ssRNA genome is capped by VPg and has a Poly A tail.
How do polio viruses enter host cells?
Their viral proteins (especially VP1) interact with host receptor molecule CD155/necl5, which triggers host receptor mediated endocytosis.
What is the significance of the host’s response of acidifying the endosome after uptaking poliovirus through receptor mediated endocytosis?
In acidic conditions, CD155/necl5 if attached to VP1-3 will undergo a structure change and create a pore in the capsid, allowing the viral genomic contents to be dumped out.
What is the function of polio’s Internal Ribosome Entry Site?
Polio’s IRES tricks our host initiation factors into binding and jumpstarting translation.
True or false: a hallmark of poliovirus is that it can survive the acid in our stomach.
True
How does poliovirus ensure that its proteins appear at temporally appropriate times?
Polio’s proteases have limited autoproteolytic activity, but their activity increases and the polyprotein is broken down. This makes polio’s proteins appear in waves, as the massive polyprotein is sequentially degraded into the individual proteins.
True or false: the poliovirus genome is polycistronic.
False. It’s monocistronic
Does VPg have anything to do with translation?
No. It’s a nuclear protein that functions as a primer for transcription and replication once inside the host.
Where does poliovirus replicate?
In the cytoplasm.
True or false: poliovirus uses the host’s nucleus during replication.
False. It uses only the cytoplasm
