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210 Cards in this Set

  • Front
  • Back
What is the structure of the herpes structure?
ds DNA of 125-229kbp
icosahedral symmetric capsid
162 capsomeres
teguments
envelope membrane from host
ds DNA of 125-229kbp
icosahedral symmetric capsid
162 capsomeres
teguments
envelope membrane from host
How long can herpes virus remain in its host?
lifelong
What is the epidemiology of herpes virus?
Around 30-50% middleclass population are infected with herpes.
Whereas 80-100% of pooerer population are infected.
How many kinds of human herpes virus are there?
8
Describe HHV6 and HHV7?
1 in 6 are infected
passed from mother to child
Both cause roseola in children
infect T cells
Describe Kaposi sarcoma associated herpes virus
Mostly seen in immunocomptromised patients
Describe Epstein Barr virus
Infects B cells and is the main causative agent of infectious monocucleosis (sore throat, fever, fatigue)
Describe Cytomegalovirus
Amphitrophic. Mostly affects infants and immunocompromised
Describe HSV1, HSV2, and Varicella-zoster virus
Infects skin and nerves, and remains latent in the sensory neural ganglia. HSV causes labial and genital diseases whereas VZV causes chickenpox and zoster (zone of blisters)
Contrast HSV1 and HSV2
HSV1 causes less urogenital infections
HSV1 causes more labial infections, ocular keratitis, encephalitis, meningitis => more infections in the head region
HSV1 causes less neonatal infections
What are symptoms of herpes infection?
prodrome of pain
core sore
gingivostomtitis
How long is the incubation of herpes?
2-12 days
What is the treatment for herpes infection?
It is self limiting in immunocompetent people

We can use acyclovir, famciclovir, or valacyclovir
What causes reactivation of herpes from the sensory ganglia?
stress
UV
concurrent infections
What does herpes look like?
Starts as a blister
Develops into crust

herpes infection appear along a nerve root (dermatome)
Starts as a blister
Develops into crust

herpes infection appear along a nerve root (dermatome)
How are veneral disease transmitted?
Through sex. It requires the warm temperature and the moisture to protect its fragile structure.
How long is the incubation of varicella?
14-15 days
Which is more severe: varicella in adult or child?
adult
What are the symptoms for chickenpox?
fever, chills, myalgia, rash
What is progressive varicella?
A rare condition found 10-20% of pregnant women where the virus gets into the lungs, brain and other organs causing pneumonia , meningoencephalitis...
What is zoster?
localized recurrence of herpes virus lesion. These lesions are unilateral.
What are the symptoms for zoster?
pain, itch, and visible vesicles
What is the epidemiology of zoster?
Occurs more in the elderly
Where is VZV laying latent in the body?
Spinal ganglion
What is the trigeminal nerve
Nerves permeating the face. There are 3 branches; one controlling the eyes, one the cheeks, and one the jaw.
Nerves innervating the face. There are 3 branches; one controlling the eyes, one the cheeks, and one the jaw.
What is the difference in diagnosis between chickenpox and smallpox?
chickenpox is more localized in the core of the body whereas smallpox is distributed to the limbs

chickenpox does not leave scars
What is the greatpox?
syphilis
How do we treat itchiness of herpes infection?
Calamine lotion
What is cytomegalovirus?
HHV5. A herpes virus which is not known to cause disease in immunocompetent individuals.

May cause rare congenital disease: mental retardation

Causes fever, hepatitis, pneumonia in transplant patients

Causes retinitis, pneumonia, esophagitis, and disseminated infections in AIDS patients
How is CMV spread?
Vertically, From mother to child through maternal blood and/or breast milk
What is the epidemiology of the CMV?
generally around 60-80% of the population is infected
What is the Epstein Barr virus?
HHV4, aka kissing disease.
How is EBV spread?
saliva
What is the epidemiology of EBV?
90-95% of the population is infected
What is acute infectious mononucleosis?
A syndrome mainly caused by EBV:
fever, sore throat lymphadenopathy

splenomegaly, hepatomegaly, palatal enanthem, jaundice, rash

mononucleosis and atypical lymphocytosis
How do we diagnose acute infectious mononucleosis?
Monospot test
What is African Burkitts's lymphoma?
carcinoma found in EBV infected Africans who are constantly being reinfected with malaria
How is EBV induced infectious mononucleosis characterised?
Early excess B cell and late excess T cell
(limited polyclonal B cell lymphocytic leukemia)
What is the Kaposi sarcoma virus
KSV causes vascular neoplasm mainly found in immunocompromised individuals
Describe HSV life cycle
membrane fusion releases nucleocapsid

capsid with tegument migrates using microtubules to nuclear pores

DNA is injected into cell nucleus and genome replication occurs in nucleus

protein created by mRNAs are delivered into the nucleus and the virus is assembled there

constructed virus are released, through the ER, by means of vesicles

vesicles membranes fuse with cytoplasmic membrane of the cell releasing the virus
Explain the reactivation of herpes virus
virus is transported from the cell body of the neuron

virus is released at the terminal end of the axon and reinfects skin cells at the primary locus of infection
Describe latency associated trascript
Prevents apoptosis of the neuron
What is acyclovir
Non phosphorylated guanosine analogue antiviral drug

3' hydroxyl group is phosphorylated by HSV thimidine kinase and becomes incorporated during DNA replicated
Non phosphorylated guanosine analogue antiviral drug

3' hydroxyl group is phosphorylated by HSV thimidine kinase and becomes incorporated during DNA replicated
What is AST a sign of?
Liver cell damage/ destruction
What is alkaline phosphatase?
Enzyme found in cells that line the biliary tract. When ALP is elevated it signifies obstruction or damage to the hepatic bile ducts.
What is the course of Hepatitis B complication?
Acute hepatitis
Chronic hepatitis
Cirrhosis
Portal hypertension and hepatocellular carcinoma
How do we treat portal hypertension and hepatocellular carcinoma?
Liver transplantation
What is liver cirrhosis?
Fibrotic tissue becomes distributed over the entire liver
How many types of hepatitis are there?
6 (From type A to F)
What causes HAV
picornavirus ((+)ssRNA)
What causes HBV?
hepadnavirus (dsDNA-RT)
What causes HCV?
flavivirus (((+)ssRNA)
What causes HDV?
delta virus ((-)ssRNA)
This is a satellite virus of hepadnavirus
What causes HEV?
Calicyvirus ((+)ssRNA)
What causes HFV?
unknown
which hepatitis are transmitted through blood?
HBV, HCV, HDV
What is the incubation duration for hep A?
2-4 weeks
What is the long lasting effects of HAV?
There are no long lasting effects of HAV. Its pathology are self limiting.
What are the risk factors for HAV?
There is no risk factor for HAV. Most attacks are on younglings of 5-14 years old.
What are the major proteins in hepadnaviruses?
S, P, C (,X)
What are the risk factors for HBV?
Druggies
Sexually promiscuous people
Sharers of intimate personal hygiene products
Which part of the body can you find the most HBV ?
Blood (serum)
What are the 3 modes of transmission of HBV?
sexual
parenteral
perinatal
Where do we find the most HBV cases?
Sub Sahara Africa
Northern South America
South East Asia
Northern North America
How are most chronic cases transmitted?
perinatally
What is the rate at which acute HBV virus become chronic?
10%
What are some drugs used to treat HBV?
Interferon
Lamivudine
Adefovir
Entecavir
Telvivudine
How is the HCV genome divided?
Structural (5') and Nonstructural (3')

There are 3 major S proteins and several NS proteins that require host and viral protease
What are the risk factors for HCV?
Drug abusers
Contact with blood
Why did HCV infection rate drop around 1988?
Blood screen for blood transfusion was available
Describe the progression of HCV from acute to chronic infection
Acute symptoms appear
Virus level heightens after 4 weeks
Virus level diminishes after 4 months
Virus undergoes quiescent phase
Virus may reemerge to cause liver cirrhosis and liver cancer
What is the rate at which HCV infections become chronic?
80-90%
Describe the epidemiology of HCV
170,000,000 are infected world wide
transmission is primarily through contact with blood
Contrast HBV and HCV
HBV transmission rate is high through sex
HBV perinatal transmission is high
HBV's progression to chronic is 10% vs HCV's ~85%
What are symptoms of acute HCV infection?
It is clinically undetectable
How do we treat HCV?
IFN alpha injection (with ribavirin in chronic infections)
NS3 protease inhibitor
Is HCV curable?
It will very soon be curable because combination drug therapies are very successful
Is there a vaccine for HCV?
No, HCV elicits too small a response therefore no protective immunity

Moreover HCV mutate easily in antigenic domains
What surface antigen does delta virus have?
HBsAg (S,M, and L), hepatitis B surface antigen
There are two type of RNA products the delta virus genome can make, what are they?
Antigenome (+) used to replicate genome
mRNA (+) used to translate into proteins
Why is delta virus viroid like?
Rolling circle replication
repetitively transcribed into many consecutive tandems
self cleavage allows tandem separation
What is hepatitis E correlated with?
Severe bowel infections
How is hepatitis E transmitted?
fecally contaminated water
Where was Hendravirus first found?
In horses with flu-like illness in Brisbane
What is the origin of the Hendra virus?
Fox bat
How do we rapidly identify emerging infectious agents?
Automated PCR

can analyze more than 1,500 PCR reactions in 24 h
How did horses get infected by bat derived Hendra virus?
Contamination of pasture by bat fetal tissues and fluids
What are the symptoms for Nipah virus infection?
fever, headache, drowsiness, pain, nausea,  vomiting, weakness, problems with swallowing and blurred vision encephalitis
Where does Nipah virus come from?
Bats that suck on tree sap pots on trees
What is the spillover host for Nipah virus? what is it for Hendra virus?
Pigs for Nipah virus
Horses for Hendra virus
What is the paramyxoviridae?
(-)ssRNA virus
Paramyxoviridae have what kind of membrane surface proteins?
F (fusion) protein
G (attachment) protein
What are the N, L, P proteins of the paramyxoviridae?
Transcriptase complex
What is the replicative cycle of the paramyxoviridae?
(-) strand makes (+)mRNA

mRNA produces proteins which will turn on full length (+) transcripts

(+) are transcribed into (-) strand
(-) strand makes (+)mRNA

mRNA produces proteins which will turn on full length (+) transcripts

(+) are transcribed into (-) strand
What is special about the genome of the paramyxoviridae?
There are intergenic regions?
What are intergenic regions?
These are U filled stretches

When transcribed, the A-U interactions are weak
=> transcription here is unstable
=> causes polymerase to fall off or stutter
What pathology does Henipavirus cause?
chronic meningitis/encephalitis

may remain latent in the brain or lung for a decade
Other than Henipavirus, what is another paramyxovirus?
Measles virus
What pathology does measles cause?
Subacute sclerosing panencephalitis
In which population are subacute sclerosing panencephalitis found?
children and young adults (6-15 y.o.)
What are the symptoms for subacute sclerosing panencephalitis
progressive psychoneurological deterioration,  personality change, seizures, myoclonus, ataxia, spasticity, coma.
How does measle viruses remain undetected by the active immune response?
Measle viruses have a membrane fusion protein which allows it to fuse the currently infected cell with another neighbouring cell. This allows it to remain within host cells at all time.
What causes subacute sclerosing panencephalitis?
An accumulation of measles capsid in neurons.

This accumulation is caused by a viral mutation that restricts expression of M proteins. Without this protein the virus cannot bud.
What pathologies does EBV cause in immunosuppressed patients?
nasopharygeal carcinoma, gastric carcinoma, Hodgkin's lymphoma, B cell lymphoma
What pathologies does parvovirus cause?
The fifth disease (Erythema infectiosum) in children
Red blood cell aplasia (Reticulocytopenia)
What causes MALT non Hodgkin's lymphoma?
Bacteria that stimulate prolonged lymphoid proliferation

examples of such bacteria:
Helicobacter pylori (gastro)
Campylobacter jejuni (small bowel)
Chlamydia psittaci (ocular)
Borrelia burgdorferi (cutaneous)
What pathologies can HCV cause?
Marginal-zone lymphoma
What is HTLV 1?
ssRNA-RT
Describe the HTLV replication cycle
Envelope receptor binding
Capsid entry into cytoplasm
RNA reverse transcription
Capsid localization in the nucleus
DNA integration into host
Viral genomic RNA transcription
Protein translation
Virus assembly
Virus budding
How can we describe the symptoms relating to non Hodgkin's lymphoma?
Different levels of CD4 T cells abundance will lead to different pathologies (from least to most severe):

Burkitt's lymphoma (B cell lymphoma)
Immunoblastic (worsened Burkitt's)
Primary CNS lymphoma caused by EBV
What is HAART?
Combination antiviral therapy to treat AIDS
What is the effect of HAART on non Hodgkin's lymphoma?
It decreased the rates of non Hodgkin's lymphoma

PS. small decrease in Hodgkin's lymphoma as well
What are the symptoms of non Hodgkin's lymphoma?
Aggressive B cell neoplasm
High LDH
Extranodular presentation
What is the Multicentric Castleman disease?
B cells hyperproliferate at multiple locations

features:
Inability to class switch immunoglobulins
HHV8 is present

causes:
fever and splenomegaly
lymphadenopathy
Pancytopenia
Elevated IL-6
Polyclonal hypergammaglobulinemia
What causes Castleman disease?
HHV8, HIV and HBV together
What are the two types of Castleman disease?
Unicentric - grows at one place
Multicentri - dispersed growth
How do we treat Castleman disease?
Unicentric - surgical removal

Multicentric - cortisone, Splenectomy, ART, Anti-IL6, Anti herpes drug (ganciclovir and cidofovir), CHOP-Rituximab
What pathologies does HHV8 (Kaposi's sarcoma-associated herpesvirus) cause?
Karposi's sarcoma
Castleman's disease
Primary effusion lymphoma
Extracavitary primary effusion lyphoma
What are some HHV8 oncogenic factors?
LANA-1, v-cyclin, v-FLIP, vIRF-3, v-IL6
What is primary effusion lymphoma?
Lymphoma that typically occur in body cavities such as the pleural space, pericardium, and peritoneum.

B cell markers:
negative: CD19, Cd20, CD79a,and lack Ig expressions
positive: Ki67, CD30, CD138
What is primary CNS lymphoma?
Lymphoma in the CNS found in very advanced HIV patients (CD4 <50)

usually EBV positive
cerebral nodules
How do we treat for Primary CNS lymphoma?
ART
What are the two gastroenteritis viral causative agents?
Rotavirus
Norovirus
What is gastroenteritis?
acute infectious syndrome of the stomach lining and the intestine

symptoms: diarrhea, vomiting, abdominal pain, nausea, fever, and chills
What can cause gastroenteritis?
Viruses- rota virus, adenovirus, calicivirus, astrovirus
Bacteria - E coli, salmonella, shigella, cholera
Parasites - Giardia lamblia, Entamoeba histolytica, Cryptosporidium
What are the ways by which pathogens induce gastroentritis?
toxins
What is the impact of diarrhea on public health?
2 million deaths annually of children under 5 years old
What is the treatment for diarrhea?
rehydration
What is the difference between Rotavirus, Adenovirus, Calicivirus, and Astrovirus?
They cause disease in people of different ages;

Rotavirus - 3-15 months old
Adenovirus - 0-2 years old
Caliciviruses - all ages
Astrovirus - infants, young children and elderly
Describe rotavirus
non enveloped
iscosahedral capsid with two protein shells (inner, outer)
11 segments of dsRNA
How many kinds of rotaviruses are there?
7 (A-G)
Is there a vaccine for Rotavirus?
Yes, Rotarix and RotaTeq.
What special about the genome of the rotavirus?
It has 11 segments and 2 of which have alternative initiation sites

There are 4 non-structural proteins with one of them have one of the alternative initiation
How does rotavirus mediate pathology?
enterotoxin
What makes up the outer layer of rotavirus?
VP4 and VP7
Describe the entry of rotavirus
VP4 -> VP8* and VP5*
entry process using VP8* and VP5* loses outer layer
double layered particles are released into cytoplasm
What can remove the outer layer of the rotavirus artificially ?
calcium chelator like EDTA
What does VP5* interact with?
integrins
What does the VP8* interact with?
sialic acid
What is the role of VP6?
to link VP7 to VP2
What is the role of the double layer protein (DLP) ?
to transcribe the RNA located in the inner core
What is the role of VP1?
It is the RNA dependent RNA polymerase RdRp

There are 4 channels in VP1;
1 channel for template input
1 channel for (+!)RNA output
1 channel for (-) RNA output
1 channel for NTP input
What is the role of VP3?
guanylyl and methyl transferase
(5' cap adder)
What is the role of VP2?
It is the capsid
What is significant about norovirus?
Account for 90% of nonbacterial gastroenteritis
Describe norovirus
Non enveloped
icosahedral virus
(+)ssRNA
How many types of noroviruses are there?
5 genogroups (GI - GV)
Which are the main genotypes of norovirus?
GI and GII
What is the Norwalk virus?
GI norovirus, the first viral gastroenteroitis causative agent
When is the virus shedded?
Before the onset of illness and continues lon gafter the illness
What are the surface proteins of norovirus?
S, P1, P2 (from inside to outside)
Describe the replication cycle and transcription process of norovirus
(+) genomic RNA makes full (-) transcript
(-) can transcribe full length (+) genomic RNA or subgenomic RNA for proteins
What are (+)transcripts capped with in norovirus?
On both (+) genomic RNA and subgenomic RNA there is a protein cap called VPg used as a primer for transcription
What is the receptor for norovirus?
Histo-blood group antigens found on RBC, gut, respiratory epithelia
What are the major groups of histo blood group antigens
ABO, Lewis, and secretor families
What on the norovirus binds the HBGAs?
P2 subunit of VP1 surface protein
To which part of HBGA does norovirus bind?
ABO - Gal/GalNAc, alpha-1,2Fuc
(Galactose/N-Acetylgalactosamine, Fucose-alpha1,2)

Lewis - alpha-1,2Fuc, alpha-1,4Fuc
(Fucose-alpha1,2 , Fucose-alpha1,4
What are some host factors affecting susceptibility to norovirus?
non secretors are resistant to infection
What are non secretors?
Nonsecretors do not have a functional fucosyltransferase 2 gene.
What is the impact of respiratory diseases?
16% of death in Canada
18% mortality for children younger than 5 years of age (leading cause)
15% of all cancers in lung cancer
6-7% of world population has asthma
1.8 million deaths annually by TB
3-4 million deaths annually by acute infectious respiratory diesease
What are the two types of respiratory infections?
Upper and lower respiratory tract infection
Contrast upper and lower respiratory tract infection
LRTI leads to lack of breath and 1-2% of these require hospitalization whereas URTI involve typical cold symptoms.
What are the two ways virus can cause pathology?
viral factors and immune factors
How do we treat viral respiratory infections?
Antivirals
Vaccines
Antibiotics (for coinfections)
Bronchodilators, corticosteroids
What is the main cause of bronchiolitis?
Respiratory syncytial virus RSV
How often is there coinfection in respiratory infections?
20%
Describe rhinovirus
noneveloped picornavirus
(+)ssRNA
accounts for 50% of common cold
trophic for respiratory epithelium
What are the two types of Rhinovirus
hRV-A and hRV-B serotypes
What are the receptors for rhinovirus?
ICAM1, LDLR
How do we treat rhinovirus?
There is no medication available becuase it is self limiting
Describe coronavirus
enveloped coronaviridae
(+)RNA
accounts for 10-30% of common cold
tropic for upper respiratory tract and GI tract
Where is coronavirus assembled?
golgi
Describe Adenovirus
Non-enveloped adenovirdiae
icosahedral capsid
dsDNA
accounts for 3-5% of infections in children
accounts for 2% of infections in adults
tropic for respiratory tract, gastroentral, liver
Describe Reovirus
Non-enveloped reoviridae
icosahedral capsid
dsRNA (10 segments)
does not cause disease in humans
Describe parainfluenza virus
Enveloped paramyxoviridae
(-)ssRNA
carry HA and NA
What is the treatment for parainfluenza virus?
There is no medication for parainfluenze virus
What is the difference between parainfluenza virus and influenza virus?
parainfluenza virus' genome has one segment
influenza virus genome has 8 segments
Describe respiratory syncytial virus
enveloped paramyxovirus
(-)ssRNA
affects mainly elderly and immunocompromised
2/3 of infants are infected during their first year
90% of infants are infected one or more times by their second year
How do we treat respiratory syncytial virus
There is no medication
What is the route of infection of RSV?
aerosol and direct contact through the nose and eyes
What are the symptoms of RSV infection?
rhinorrhea
cough
fever
bronchiolitis
air trapping
wheezing
pneumonia
necrosis of epithelial cells
What are the types of RSV?
There is only one serotype of RSV
What is a syncytium?
A fused cell caused by RSV
What membrane protein mediates entry for RSV?
G protein
How does RSV escape active immune response?
By heavily glycosylating its G protein and 80% of G protein is secreted to neutralize antibodies.

Moreover the immune response in the respiratory tract is weak. Local IgA response are short lived. Serum antibodies are less effective, having to travel far into respiratory lumen. Infants themselves have a weaker immune system.
Describe RSV entry process
G protein binds heparin or proteoglycans
F protein fuse membranes
What does SH protein do?
viroporin and inhibits apoptosis
What do the RSV NS1 and NS2 do?
inhibit IFN induction and signaling
Hendravirus is another paramyxovirus. What is its membrane protein and what is its receptor?
Its surface protein is also the G protein however its receptor is the EphrinB2 and EphrinB3
Describe the RSV replication cycle and transcription process
(-)RNA genome is transcribed into both mRNA and antigenome
(+)RNA antigenome is transcribed back into (-)RNA genome
How is virus detected in the cell?
RIG I pathway will produce IFNalpha/beta
IFNalpha/beta will activate the JAK/STAT pathway through IFN receptor
How is RSV detected in the cell?
Extracellular: TLR2/6, TLR4
Endosome: TLR3
Cytoplasm: RIG I
How does RSV evade the detection inside the host cell?
NS2 inhibits RIG-I and NFkappaB and JAK-STAT pathway
NS1 and NS2 inhibit IRF3
Describe influenza virus
Enveloped
(-)ssRNA (8 segments in influenza A, 7 in C)
has HA and NA
What are the different types of influenza viruses?
Influenza A - human, pig, bird, horse
Influenza B - human, seal
Influenza C - human, pig

Influenza A and B are major causes of human epidemics
How many types of HA and NA are there?
There are 16 HA and 9 NA
What are the two ways influenza can mutate?
Antigenic drift and reassortment
What is a mixing vessel?
An intermediate host that express both human and animal influenza virus receptor

for example pig has both human and avian type influenza virus receptors
What is the spanish flu?
H1N1 which killed 50 million people
high mortality rate in young addults
people dies from pneumonia and viral pneumonia
caused by immunopathology
HA and PB2 contribute to virulence
Where did H1N1 come from?
From North American avian flu to classical swine flu to human H3N2 and Eurasian avain like swine flue
Describe the influenza virus life cycle
Entry through binding sialic acid
Escape from endosome
Enters the nucleus
Exports mRNA and genomic RNA
What is the difference between avian and human sialic acids?
Avian - sialic acid alpha 2,3 galactose (GI tract)
Human - sialic acid alpha 2,6 galactose (Tracheal)
Pigs - tracheal tissue has both
What determines the receptor specificity for the specific sialic acid
Receptor specificity is determined by amino acid residues of the HA receptor binding pocket
What is HA maturation?
Cleavage of HA0 into HA1 and HA2 by host protease at basic amino acid residue. There is only one protease for a specific locus in each type of tissue.

Influenza viruses with multiple basic amino acids allows infection in different tissues
What is the helix bundle?
It is a 6-helical structure to pull the two membranes together to cause fusion
What is the influenza polymerase complex composed of?
PA, PB1, PB2

PB2 grabs 5' caps of host mRNA
PA cleaves the cap
PB1 will elongate the viral mRNA using the stolen cap
How is the influenza virus assembled?
HA and NA binds to lipid raft domain on the plasma membrane

8 pieces of RNA is packaged

M1 and M2 completes the assemble and budding
What does influenza NS1 do?
limit IFN through inhibition of RIG I, PKR/PACT
limit antiviral state of host cell through inhibition of OAS
block cellular mRNA maturation and export of premRNA
enhance viral mRNA maturation
How does antiviral work against influenza?
Zanamivir and oseltamivir blocks sialidase to block exit
Amantadine M2 protein to block entry
What kind of vaccines are available for influenza?
Seasonal flue vaccines
Seed virus
Inactivated virus
Live attenuated vaccines
Highly conserved membrain antigens (M2 protein)