Exam 2 - Viruses Flashcards
(189 cards)
1
Q
Why are viruses considered “obligate intercellular parasites”?
A
They can only replicate inside of a host cell
2
Q
Difference between a virus and a toxin
A
A virus cannot replicate itself even in a host cell
3
Q
Filter experiment for tobacco mosaic viruses… Who? When?
A
Ivanofsky, 1892
4
Q
Growth shown in tobacco for tobacco mosaic virus… Who? When?
A
Beijerinck. 1898
5
Q
What are bacteriophage? Who discovered them? When?
A
Bacteria viruses, discovered by Twort in 1915
6
Q
Animal viruses were first discovered with ________ disease. When was first human virus discovered? What virus was it?
A
Animal viruses were first discovered with ‘Foot and Mouth’ disease in 1898. First human virus discovered was ‘yellow fever virus’ in 1901
7
Q
Cellular origin theory of viruses:
A
viruses were once cellular components but over time they evolved separately
8
Q
Autopoitic theory of viruses
A
Viruses once auto poetic entities but become reliant on other cells over time
9
Q
What is an envelope?
A
A virus modified cellular membrane that is picked up from a host cell as a virus exits. These can be easily identified because they are susceptible to lipid solvents and in the presence of them, the virus is non-infectious.
10
Q
Advantage of being a small virus?
A
replicate genome multiple times befell cell recognizes that it is infected b/c can replicate faster
11
Q
Advantage of being a large virus?
A
can carry more genes or proteins that can help the virus. Ex: can have immune modulators that can down-regulate the host inmate immune response or turn off the antibody response.
However, a larger genome requires more time to replicate
12
Q
What is a (+)sRNA vs (-)ssRNA? Ambisense RNA?
A
(+)ssRNA can be used to make viral proteins immediately. (-)ssRNA needs to be used as a template to make (+)ssRNA that can be used for proteins.
Ambisense is part (+) and part (-)
13
Q
Segmented genome?
A
for virus to be complete, all the segments of the viral genome must be packaged up and put into a single virus particle.
14
Q
Smallest genome?
A
Picornovirus (polio)
15
Q
How does ssDNA replicate?
A
ssDNA Relies on the host cell’s replication machinery but that machinery looks for a dsDNA. So, the genome will fold together to a double stranded “hairpin” that serves as signals for host machinery to sit down and start making the copies.
16
Q
How does dsDNA replicate?
A
dsDNA has a nick-site where DNA repair mechanisms sit down and make repairs. As that repair is completed, a rolling cycle of replication similar to host cell normal dsDNA replication occurs.
17
Q
How does (+)ssRNA replicate?
A
(+)ssRNA (ex: picornovirus) goes straight to the ribosomes once it is injected into the cell. It begins translation process immediately and makes RNA-dependant RNA polymerase that will be able to make a negative strand template that can be used to make additional copies of the genome.
NOTE: you don’t need any virus particles of picornavirus to get replication and production of virus particles for this reason. The (+)ssRNA is enough of a self-starter all by itself.
18
Q
How does (-)ssRNA replicate?
A
(-)ssRNA must enter the host cell with a RNA-dependant RNA polymerase that can turn the (-) strand into a (+) strand that can subsequently make proteins. Eventually the (+) strands of genome will be used as templates to make (-) progeny genomes.
19
Q
In general, what do DNA viruses need that RNA viruses don’t need?
A
DNA viruses need access to the nucleus. Often they are tumorigenic, meaning the keep the cell mitotically active so that there is access to the nucleus.
DNA viruses also need access to the host replication machinery
20
Q
What do RNA viruses need that DNA viruses don’t need?
A
RNA need RNA-dependent RNA polymerase.
21
Q
Sometimes one receptor is not enough to facilitate virus attachment and entry, and a _______ is needed.
A
Co-receptor (Ex: HIV)
22
Q
What allows attachment and infection?
A
Attachment sequences
23
Q
What is Tropism
A
By taking one type of virus and changing the surface proteins you can change what the virus can infect. What the virus can infect / types of cells / tissues is its tropism.
24
Q
What is zoonosis?
A
Viruses that infect humans and inimals, but are not able to infect other more divergent hosts like plants, bacteria, and fungi.
25
What was the major reason that we were able to eradicate smallpox? (think tropism)
It is only a human pathogen. Yellow fever is in humans and mosquitoes so it is hard to get rid of.
26
What is receptor-mediated endocytosis?
Trigger the cell to take the virus into the cell as if something good is on the source of the cell by confusing it for something else that the host cell does normally take inside.
Note: Direct penetration of plasma membrane is also possible
27
Non-enveloped viruses mode of entry VS enveloped viruses mode of entry:
Non-enveloped not as well understood:
- Picornavirus (causes polio) makes pores in the membrane
- Adenovirus and Reovirus cause membrane disruption. Proteins are present that can go in and make a large enough hole in the membrane to be able to pass the nucleocapsid through the hole.
Enveloped: viruses goes through membrane fusion. (best understood for influenza so use the Hemaaglutinen protein to show attachment and fusion...
28
Describe how Influenza virus enters the cell
Uses the hemaglutenin proteins to attach and fuse to the membrane of the host cell. Once the virus is taken in by endocytosis and when it is in the endosome the pH will start to drop. When the HA proteins is exposed to the pH drop it undergoes a conformational change and injects part of its receptor protein into the cellular membrane which will bring the cellular membrane and the viral membrane into close proximitity. This results in membrane intermixing. You then get a fusion state and a full pure forming and then finally once it is able to gain access to the cytoplasm it has to deal with the rest of the replication cycle.
29
What type of viral genome does not ever release its genome out to the host cell?
dsRNA
30
What type of viral genome usually rely upon cellular RNA polymerases.
DNA genomes
31
What type of viral genome must bring its own polymerase into the cell?
(-)ssRNA and dsRNA
32
What type of viruses must use host cell ribosomes?
All viruses must use host cell ribosomes!
33
Structural proteins are produced in high levels but non-structural proteins are only see inside the host cell. (T/F)
True
34
How does dsRNA replicate?
Virus particel include the viral polymerase dn the dsRNA does not leave the virus particle. mRNA gets produced and then is exported to the cytoplasm where the mRNA serves as a template for making proteins. Then the cell makes empty protein capsules. A (+) gets brought inside and as it is brought in, it is used as a template to make the (-) strand. Thus, yielding the dsRNA.
35
Why are poxviruses an exception?
They replicate in the cytoplasm and they have their own DNA polymerases needed to execute their transcription and replication process.
36
What are cellular viral factories?
Localized structural proteins to aid assembly. You get dense pockets of virus particle that are assembled in the same location. The genome will contain packaging signals and the proteins will recognize progeny genomes that will grab onto them and the capsid will assemble around it or the capsid will assemble empty and it will find genetic material to import inside the particle itself.
37
How does adenovirus package?
Adenovirus starts as an empty protein coat that grabs the genome and pulls it inside.
38
How does Reovirus package?
Reovirus starts with RNA packaged during capsid assembly and it will synthesize the (-)RNA strand on top of the (+) that is already in the cell
39
How do Retroviruses package?
Retrovirus has proteins that grab onto the genetic material itself and the capsid gets assembled around the progeny genomes
40
What is lysis
Ability to rupture the cell and dump contents out of the cell. This is likely to make a big immune response though because of all the cellular debris.
41
What is weak lysis?
The virus replicates and consumes all the raw materials inside the cell so that cell cannot maintain its membrane and its proteins. This leads to the cell deteriorating and then the cell eventually breaks open in a more passive way.
42
What is budding?
Budding for enveloped virus when the nucleocapsid comes near the cell membrane and induces the membrane to form around the capsid and then pinch off the virus into the extracellular space
(this is how HIV works! Influenza also does this, but Zanamivir/Tamiflu blocks the release of budding virions!)
43
Advantage to lytic vs non-lytic infections?
Progeny can more quickly be released to go infect more cells in lytic cycle. The lytic cycle also has a higher chance of triggering immune response because all the parts of the host cell are also getting ejected into the extracellular space
44
What is the normal multiplicity index for a 1-step growth curve?
5x the virus particles / cells to infect
45
Eclipse phase of 1-step growth curve:
Attachment and uptake causes a decrease in initial concentration of infectious particles. Particles are inside the host cells and are replicating
46
Exponential growth phase of 1-step growth curve:
Replication and assembly is completed and causes a great increase in the number of virus particle that are available for infection of new cells
47
Plateau phase of 1-step growth curve:
All the cells resources are used up and there is no more ability to make more virus particles and/or all the host cells have been lysed
48
Time of 1-step growth curve is variable:
bacteriaphage: 30 min
Vesicular somatitis virus ~6 hours
Vaccina (smallpox virus) ~24 hours
49
Productivity of 1-step growth curve is variable
Vesicular somatitis virus 1:1,000
| Vaccina produces 1:100
50
Confirmation of the virus / disease causing agent: Huff's Principle
Putting the virus back into eggs, cell culture, etc. to show that the virus makes more of the virus.
51
Hierarchy of numerical detection/quantification
Physical (counting particles)
Infectivity
Genomic (PCR)
Serological (antibody reaction)
52
Ways to look for infection assays:
Look at Cytopathic effect (CPE) - look for rounding, syncytial formation and/or inclusion bodies. This happens in cells infected with virus.
Flourescence assay
Plaque assay
Infectious dose assay
53
Particle assays / Hemagglutinin assay
Use plates with RBCs and virus. Where not enough virus the RBCs will pelt. Where there is enough virus to make a matrix then you will get a fuzzy appearance and there will not be a pellet. The concentration where it changes between polluting and non-pelletting you can calculate a value.
54
Different assays give different numerical values!
Direct electron microscope count highest then infectivity then plaque formation then hemagglutination is less still. Plaque forming units can range from 1:1 to 1:10,000 virus particles.
55
Viruses are __________ and use the host cell's replication processes to duplicate themselves.
Obligate intercellular parasites
56
Human viruses range in size from ____ to ____
30nm - 300nm
57
Virus are classified by the ________ , ______ , and the _______
Genome, particle structure, and replication strategy.
58
What viruses are primarily associated with children?
```
Measles virus
Respiratory Syncytial Virus
Varicella Zoster Virus
Rotavirus
Poliovirus
```
59
What family is Measles virus? What else is in this family?
Paramyxovirus (also Measles and also mumps virus)
60
What is measles genome?
(-)ssRNA
61
What is measles genome shape? Enveloped?
Helical ; Yes, enveloped (same as RSV, b/c same family... paramyxovirus)
62
Where is measles replicated?
cytoplasm
63
How does measles virus exit host cell?
budding
64
What causes syncytial formation? (especially in measles virus)
Fusion protein
65
How is measles spread?
inhalation of aerosolized droplets from coughing/sneezing
66
What is the characteristic symptom of measles?
"Koplik spots" which are red spots with a bluish middle to them. It is caused by the virus and immune response to damage to epithelial and endothelial cells
67
Describe the process of measles infection/spread
Measels virus first infects respiratory epithelial cell. It then enters the blood stream from the lungs and causes the primary viremia and spread to many locations of the body and begins to cause disease symptoms.
Once it spreads to the spleen, it can cause a secondary viremia b/c blood is passed through the spleen.
68
What is incubation period for measles? Recovery period?
Incubation period is 10-14 days
| Recovery is 20 days after infection
10% mortality
69
What complications does measles virus cause?
Opportunistic infections (Strep pneumoniae, Staph aureus, or Haemophilus influenzae)
Blindness in children with Vit A deficiency
Neurological manifestations:
Acute Demyelinated Encephalomyelitis (ADEM) 1:1000
Subacute Sclerosing Panecephalitis (SSPE) 1:1,000,000 after 7-10 years. It is a progressive neurological deterioration
70
What is ADEM?
Acute Demyelinated Encephalomyelitis (ADEM) 1:1000 ; it is a rare demyelinating disease that results from measles virus
71
What is SSPE?
Subacute Sclerosing Panecephalitis (SSPE) 1:1,000,000 after 7-10 years. It is a progressive neurological deterioration Caused by measles virus
72
How is measles diagnosed?
Fever and cough for 2-3 days then Koplik Spots
73
What are the hosts for measles virus?
Only humans, but very contagious with Ro = 15-20. People are able to spread 2-3 days before rash.
74
How long does the measles vaccine convey immunity?
life-long
75
How is measles treated?
Vit A can reduce severity but there are no antivirals. Use supportive care for symptoms (ex: benedryl for rash...)
76
What family if Respiratory Syncytial Virus (RSV)? What else is in that family?
Paramyxovirus ; Measles virus. (Also mumps, caused by mumps virus... we didn't discuss this though)
77
What is the genome of RSV?
(-)ssRNA
78
What is the genome shape of RSV? Enveloped?
It is helical and yes, enveloped (same as measles b/c same family... paramyxovirus)
79
Where does RSV infect? Spread?
It infects the respiratory epithelium and stays localized there.
80
How does RSV exit the cell?
Budding
81
What is "the most important viral agent of serious pediatric respiratory tract infections"?
RSV
82
How is RSV spread?
aerosolized particles and/or fomites (door handles, etc.)
83
Incubation period for RSV? What is this relative to Measles?
Incubation for RSV is 4-5 days (measles is 10-14)
84
What are symptoms of RSV?
Upper respiratory tract symptoms then 1-3 days later you get lower respiratory tract symptoms. The immune response to the infection causes congestion and an cause difficulty breathing.
85
What is the recovery time of RSV? How is this relative to measles?
7-12 days after onset of symptoms (measles is 20 days)
86
What are the hosts of RSV? How is this relative to Measles?
Both have only humans as host, but RSV vaccine is not lifelong and so newborns have trouble with this b/c they have no immunity from mom.
87
Why is recovery for RSV fairly slow even though it is localized to the respiratory tract?
It is not very cytotoxic so it does not trigger a large immune response.
88
What are risk factors for RSV?
Daycare, older school-age siblings, premature babies, male, second hand exposure to tobacco smoke, or babies that do not get breast milk
89
What is the treatment for RSV?
No antivirals and no vaccine b/c surface antigens mutate frequently.
Passive immunoprophylaxis is when taking antibodies that against RSV virus and purify them and introduce them into the blood stream to induce a response to the infection. It will work to the extent that the antibodies are able to recognize the proteins on the surface of the virus and bind to it.
90
What family is Varicella Zoster Virus?
Alphaherpes virus
91
What is the genome for Varicella Zoster virus?
dsDNA. It is very large, makes hundreds of proteins
92
Where does Varicella Zoster replication occur?
Nucleus, it is DNA and fits the rule
93
What do the immediate-early genes do in herpes viruses (including Varicella Zoster)?
They help to keep the cell in replication-mode because the genome needs access to the nucleus.
94
Describe the cell cycle for Varicella Zoster virus
Cell attachment occurs and the nucleocapsid escapes out the endosome and makes its way to the nuclear membrane and it makes its way inside. Release and exposure of the genetic material then it gets circularized and it serves as templates for RNA. The genome is really big so you have different phases of genome expression with very early/early/late expression. Proteins then come back in and bind with the progeny genomes in the nucleus and then bud out of the nuclear membrane and transport to surface of the cell and bud from the cell.
95
Where does Varicella Zoster establish a latent infection?
Neurons, can cause shingles
96
What is mechanism of infection for Varicella Zoster?
Inhalation of aerosolized droplets.
97
What is Incubation period for Varicella Zoster?
Symptoms?
Recovery?
10-21 days.
Symptoms are generic in the beginning then rash 1-2 days after symptoms start. Rash lasts 3-6 days, PRIMARILY on the face/scalp/trunk (different than smallpox which is more extremities!).
2 weeks post symptom onset.
98
What is the most important part of immunity for Varicella Zoster?
Cell mediated immunity (WBC's, natural killer cells, etc.)
99
Prevention of Varicella Zoster?
vaccination - has life long immunity from an attenuated virus.
100
Treatment of Varicella Zoster?
Acyclovir (treats all herpes viruses)
Acts by interfering with genome replication but cannot eliminate the latent virus. It does not prevent infection of cells.
101
What family is Poliovirus?
Picornavirus (very small)
102
What is the genome of Poliovirus? Enveloped?
(+)ssRNA. Non-enveloped!
103
What is the replication cycle like for Poliovirus?
It is very small and does not go through receptor-mediated endocytosis. It permeates the membrane. It is a small genome that usually gets made into one big protein that then is cleaved. It will make a bunch of capsid material that will grab the progeny tense and will release throuhgh a weak lysis
104
How does poliovirus exit the host cell?
Weak lysis. (and it enters by permeating the membrane)
105
Where is the primary site of infection for poliovirus? What symptoms does it normally cause?
Peter's Patches of the intestines. It causes gastroenteritis there. It mostly just causes diarrhea (unless in the 1/200 cases it invades nervous system)
106
What is the major complication of Poliovirus?
If it enters the blood stream from the intestines (Peyer's Patches) it can enter the nervous system. This happens in 1:200 infections. Symptoms can e severe and replication in gray matter of the brain and spinal cord can result in limb paralysis or respiratory paralysis due to damage of the medulla.
107
What are the 2 Polio vaccines and what is different about them?
Salk - heat killed
Sabin - live attenuated
You get a better immunity with the live attenuated because there is a cell mediated and antibody response, but there is a small chance of getting the infection.
There is only a antibody response in the killed virus.
108
What family is Rotavirus?
Reoviridae
109
What is genome of Rotavirus? Enveloped?
dsRNA ; Non-enveloped and has protein layers that have different functions associated with its different parts of 'life cycle'
110
Describe the cell cycle of Rotavirus
It gains entry, goes through the endosome pathway. Then in the late endosome where the pH has robbed it breaks out of the endosome with an icosahedron that has a 5-point structure that can extrude the RNA that it makes. Assembly of new virus particle that will grab the mRNA and will import them to the interior of the new virus particle. As this happens it will synthesize the other strand. It then ends up in the ER where it gets final assembly with the outer capsid proteins and then exits the cell through weak lysis.
111
How does the Rotavirus exit the host cell?
Weak lysis
112
How is rotavirus contracted?
Ingestion of contaminated material (fecal-oral)
113
What is the incubation of rotavirus? Symptoms? Recovery?
2 days of incubation with vomiting and fever. Then diarrhea 2-3 days after vomiting, 3-8 days in duration. Virus shedding for weeks before symptoms present and days after recovery! ((So incubation is weeks????))
114
When populations does rotavirus cause most severe issues?
People who have trouble getting potable water and electrolytes.
115
Prevention of Rotavirus? Treatment?
Infant vaccine available. Also hygiene is most important.
Treatment: rehydration
116
Common childhood diseases not really discussed in detail:
Mumps caused by mumps virus (paramyxovirus, so is Measles and RSV)
German measles caused by rubella virus (toga viruses)
Fifth disease caused by parvovirus B19 (parvovirus)
Roseola caused by human herpes virus-6 (betaherpesvirus)
117
Where do Hepatitis viruses infect? Do they cause damage?
Liver hepatocytes. They don't cause much damage but the host immune system causes a lot of collateral damage.
118
What is the family of Hep A? (What other virus is of that family? What does that virus cause?
Picornaviridae (Same as Picornavirus, which causes polio)
119
Genome of Hep A? Enveloped?
(+)ssRNA; non-enveloped
120
What is the family of Hep B?
Hepadnaviridae
121
Genome of Hep B? Enveloped?
Circular dsDNA ; Enveloped
122
Family of Hep C? What other virus is of that family?
Flaviviridae (same as West Nile virus)
123
Genome of Hep C? Enveloped?
(+)ssRNA ; Enveloped
124
Family of Hepatitis delta? Genome? Enveloped?
Deltaviridae ; (-)ssRNA ; Enveloped
125
Family of Hepatitis E? Genome? Enveloped?
Calciciridae ; (+)ssRNA ; Non-envelped
126
Which Hepatitis viruses are enveloped?
B,C,Delta but not A and E
127
Which hepatitis viruses are non-enveloped?
A and E
128
Which Hepatitis viruses are (+)ssRNA?
A, C, and E
129
Which hepatitis viruses is (-)ssRNA? which is Circular dsDNA?
(-)ssRNA is Hep Delta ; Circular dsDNA is Hep B
130
Which Hep viruses are transmitted Fecal-oral?
A and E
131
Which Hep viruses are transmitted Sexually?
All! A, B, C, Delta, and E
132
Which Hep viruses are transmitted vertically?
B, C, Delta
133
Which Hep viruses are transmitted Parenteral?
All! A, B, C, Delta, and E
134
How is may Hep A be transmitted? E? (they are the same)
Fecal-oral
Sexual
Parenteral
135
How may Hep B be transmitted? C? D? (they are all the same)
Sexual
Vertical
Parenteral
136
Hep A & E are primarily associated with what transmission?
Fecal-oral
137
Hep B, C, D are primarily associated with what transmission?
Sexual and Drug use
138
Which Hepatitis viruses are chronic?
Hep B and C
139
What Hep virus is associated with food poisoning? Is it chronic or acute?
Hep A. It is acute
140
What Hepatitis virus has reverse transcriptase?
Hep B, because it's genome is dsDNA but it goes through an RNA intermediate.
141
Explain the cell cycle of Hepatitis B
The partially circularized genome gets access to the nucleus where the genome will be repaired at a nick site. The genome gets repaired to covalently closed circular DNA (cccDNA) which is the template for transcription. It makes transcripts that willead to proteins and the genome also gets replicated to make a pgRNA which is an RNA intermediate that gets reverse transcribed which results in DNA that gets packaged with the reverse transcriptase.
142
What is Hepatitis B's incubation period?
It is very long. 60-180 days
143
What is the symptom of the first round of infection by Hep B?
Jaundice and yellowing of the eyes. It also has symptoms of General malaise, anorexia, vomiting, fatigue, cough, serum-like sickness (same symptoms as Hep C, but hep C is milder)
144
What is the recovery from Hep B?
3-4 months after onset of Jaundice, but not everyone recovers. 5% of people will get a chronic disease. These people will have sporadic episodes of hepatitis and cirrhosis of the liver. Increased risk of hepatocellular carcinoma because the liver strives to regenerate itself by replicating cells. This causes more mutation and potentially cancer.
145
Vaccination available for Hep B?
Yes, it is the first recombinant vaccine approved for use in humans. Requires multiple inoculations and it is not very effective against chronic infection.
146
Treatment for chronic Hep B infections?
interferon-alpha therapy and/or nucleoside analogs (adefoir, lamivudine, tenofovir)
147
What is unique about Hep D?
It is a "subviral agent" which means that in cannot infect by itself. It needs another virus, in this case it needs Hep B. This is rare in human viruses. Only other example is aden-associated virus (AAV) which requires adenovirus.
148
Describe the cell cycle of Hep C
Genome is passed into cytoplasm through receptor mediated endocytosis and goes straight for ribosomes to be translated (it is (+)ssRNA). It makes a polyprotein that gets enzymatically broken up into nucleocapsid proteins, surface attachment proteins, etc. and also replicase. The replicase will make full length (-)ssRNA that will be the template for the genomee copies. Progeny viruses then bud out of the cell.
149
Is Hep C a chronic infection? What is Mixed Chryoglobulinemia
Yes, it is very commonly chronic. Up to 80% of infections become chronic. It can cause extra hepatic disease.
Mixed chryoglobulinemia - antibody and virus complexes deposit in other tissues like the kidneys and elicit an immune response and subsequent tissue damage (the virus travels to other tissue locations where it causes a localized infection!)
150
What is the treatment for chronic Hep C infection?
There isn't one. Once you have a chronic infection you are stuck with it. Interferon-alpha treatment can reduce chances for chronic infections though initially.
151
Does Hep A cause acute or chronic infection?
Acute
152
How is Hep A contracted?
Fecal-oral infections
153
What is the incubation of Hep A virus?
15-40 days
154
Which Hepatitis is notes as more sever in adults than in children?
Hep A
155
Hep E is significantly life threatening in what poplulation?
Pregnant women.
156
What is Hep E similar to?
Hep A
157
What are the incubation periods of the Hepatitis viruses, in order from shortest to longest?
Hep A: 15-40 days
Hep E: 21 -42 days
Hep C: 60-120 days
Hep B/D: 60-180 days
158
Which of the Hep viruses have asymptomatic infections? How often (relatively)
A,B,C,E are all often asymptomatic
| D may be asymptomatic
159
Which of the Hepatitis viruses are chronic infections?
B (5%) ; C (80%) ; sometimes D
160
Which Hepatitis viruses have long-term sequelae?
B and C, while D is an exacerbation of HBV infection
161
What family is Easter Equine Encephalitis?
Togaviridae
162
What is the genome of EEE? Enveloped?
(+)ssRNA; Yes enveloped
163
What family is VEE?
Togaviridae
164
What is the genome of VEE? Enveloped?
(+)ssRNA; Yes enveloped
165
What is the family of West Nile Virus? What other virus is of that same family?
Flavaviridae (same as Hep C)
166
What is the genome of West Nile virus? Enveloped?
(+)ssRNA; Yes enveloped
167
What is the family of the Rabies virus?
Rhabdoviridae
168
What is the genome of Rabies virus?
(-)ssRNA
*It is the only neurological virus that is not (+)ssRNA!
169
How are EEE and West Nile transmitted?
From mosquitoes and birds as a primary means of the virus but we are collateral damage!
170
Is the range bigger for EEE or West Nile? Why?
West Nile virus infects birds and mosquitoes that are more varied in their migration and location so West Nile virus is commonly found all over the country. EEE Virus is more localized to the SE because the birds it infects do not have as large of a range
171
What does it mean that EEE and West Nile require the arthropod (mosquitos) as an intermediate?
Transmission requires replication in the mosquito too. In the midgut of the mosquitoes there is infection of cells that line the gut and that generates virus particles, which make their way up to the salivary glands. So then, when the mosquito bites some of the virus is transmitted along with the saliva into the host
172
What are the 2 special proteins found on EEE and VEE? What are they for?
Proteins E1 and E2 are used for attachment and entry
173
Describe the cell cycle of EEE/VEE
Entry through the cell via receptor mediated endocytosis with eventual escape from a late endosome where (+)ssRNA serves as a template for proteins. Then get transcription/translation and get eventual spike proteins that go though the ER and the golgi and they then get to the cell surface and they bud off.
They primarily enter through the skin and infect the Langerhan's cells which then transports the virus to the lymph nodes, resulting in a viremia.
174
Does EEE/VEE cause viremia?
Yes because it goes to the blood stream/lymph through the Langerhan's Cells
175
Is EEE/VEE local or systemic? Can it be chronic or is on only acute?
It is systemic and can be chronic if there is CNS involvement (5%)
176
What is the incubation period for EEE/VEE? What are the symptoms for acute stage?
4-10 days for acute stage then symptoms last for 1-2 weeks including chills, fever, arthralgia, malaise
177
What are the symptoms of the chronic form / CNS involvement of EEE/VEE? What are complications? Fatalities?
* In ~5% of cases you can get some CNS involvement. This is where encephalitis comes in, if it makes the transmission across the blood brain barrier. This causes longer lasting, more severe issues.
* In the encephalitic disease you get fever, headache, irritability, restlessness, vomiting, diarrhea, convulsions, and coma.
* 1/3 of these cases die form the disease 2-10 days after onset.
* Those who recover can have long-term sequelae: seizures, personality disorders, or paralysis.
* Initially the infection has high virus in the primary site and the presense of the virus in the blood is somewhat delayed and then the presence of the virus in other tissues after that. Immune response delayed after that primary infection (where you get fever, joint pain, etc. in the encephalitic cases)
178
What is the prevention for EEE/VEE? Vaccine?
There is an attenuated vaccine TC-83 and a killed vaccine TC-84 but it is only given to at rick military and researchers because the recovery from the vaccine is really really rough. There is no treatment for the diseases so the vaccine is good, but it basically presents the same as the disease without the encephalytic form (no CNS involvement).
Best prevention is mosquitoes spray, etc...
179
What is the incubation for West Nile? is it normally symptomatic or asymptomatic?
The incubation period for West Nile is 2-14 days and symptoms are uncommon (20%) with most people having an asymptomatic infection. Symptoms include fever, headache, fatigue for 3-6 days.
<1% of people though get neuroinvasive disease with aseptic meningitis, encephalitis, flaccid paralysis, altered mental state, tremors. 50% of the survivors of the neuroinvasive disease have sequelae 12 months later.
180
What is the neuroinvasive part of the West Nile virus like?
neuroinvasive disease with aseptic meningitis, encephalitis, flaccid paralysis, altered mental state, tremors. 50% of the survivors of the neuroinvasive disease have sequelae 12 months later.
181
What is the prevention of West Nile Virus? Treatment?
There is no treatment and no vaccine!
182
Which of the neurological viruses are enveloped?
All of them (EEE, VEE, West Nile, Rabies)
183
Is Rabies virus of wide or narrow tropism?
Wide tropism - means it can infect many different types of cells.
184
The location on the genome of Rabies virus determines how many transcripts are made. Explain:
If you are a gene at the beginning of the genome you get more proteins made and if you are at the end of the genome gets fewer proteins made. This is because there is some probability that the polymerase will fall off of the genome so the further down the genome a gene is the more times a polymerase will have to ‘try’ to get there to make that protein
185
What is a significant protein discussed with Rabies Virus?
Binding of the N protein triggers the RNA into genome replication. It tells the cell to make progeny genomes that can be packaged into progeny virus particles. There will be a lot of defective particles as part of the infection process though because this process is fairly defective (not full length genome or maybe proteins missing like the RNA-dependant RNA polymerase).
186
How is Rabies virus transmitted? Does location matter?
Bite by an infected individual/creature is how the virus is spread. Bites on the face have a 60% transmission rate but other bites closer to 15% transmission.
187
What is the incubation period? What determines the duration of the incubation period?
The incubation is 1-3 months but varies depending on where bitten because the virus has to work its way up to the brain.
188
Describe the spread of the Rabies virus inside of a host:
Replicates locally at the site of the bite until it finds neurons. Once the virus is in a neuron it moves passively in axoplasm of the peripheral nerves to spinal ganglia, spinal cord, and brain (so shorter incubation time if bite is closer to the brain – shorter distance to travel up neurons as apposed to a bite on the leg). Then the virus spreads back to the periphery to highly innervated salivary glands and replicates. Then there is lots of virus in the saliva and it induces people to not swallow so that saliva with virus particle is spread
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Prevention / Treatment of Rabies Virus:
Vaccine available but it is only used as a post-exposure prophylaxis in the USA because rabies virus is not very common. Should be administered immediately for bites that break the skin. The vaccine is 4 doses (immediate, 3, 7, and 14 days) and should also receive immunoglobulin (RIG). This is because it takes multiple exposures to get a good immune response (therefore it is not very ‘immunogenic’)
Vaccination of dogs and domestic animals essential to control. Some countries attempt to vaccinate wildlife using baits laden with oral vaccines.
