Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Medical Microbiology > Day 3: Morbilliviruses, Noro- and rotavirus, Rhabdoviruses > Flashcards

Day 3: Morbilliviruses, Noro- and rotavirus, Rhabdoviruses Flashcards

HC06, 07, 08

You may prefer our related Brainscape-certified flashcards:
USMLE® Step 1 flashcards Biology 101 flashcards
1
Q

HC06: Measles virus (MV / MeV) is prototype member of genus …

A

Morbilliviruses, family Paramyxoviridae

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Typing MV and genome

A
  • Enveloped virus
  • (-) ssRNA, non-segmented
    > encodes 6 structural and 2 non-structural proteins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

MV genotypes and serotype

A

> 24 genotypes: A, B1-3, C1-2, D1-11, E, F, G1-3, H1-2
Few are circulating
Type A used for vaccine
Despite diversity in genotype, one serotype: implies high degree of similarity in surface antigens across all MV strains

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

6 structural proteins of MV genome

A
  • Nucleocapsid protein (N)
  • Phosphoprotein (P)
  • Matrix protein (M)
  • Fusion protein (F)
  • Attachment protein (H)
  • Large error-prone RNA-dependent RNA polymerase protein (L) > because (-) ssRNA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

2 non-structural proteins from MV genome

A

C and V
> encoded in P transcription unit
> C protein is translated from overlapping readin frame within P gene
> V protein is initiated from same start codon as P, but a frameshift is created by mRNA editing causing early stop codon as well as different protein.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

ORFs in MV genome

A

Multiple in genome
> polymerase gene at 5’
First bit converted (at the 3’ of (-) strand) becomes the 5’ (first translated) of the mRNA plus strand made

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

MV virion

A
  • large 15 kb RNA genome
  • large protein and phosphoprotein packed on RNA
  • Nucleocapsid on the RNA itself
  • Matrix proteins chains under the envelope
  • Lipid bilayer (envelope)
    Hemagglutinin and Fusion protein on surface
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Where replication cycle of MV?

A

In the cytosol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Cellular receptors for entry MV

A
  • SLAM/CD150
  • Nectin-4
  • CD46 (for vaccine strain A only)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Pathogen MV character

A
  • Causing disease in old and new world non-human primates (NHP) and humans: endemic in humans only
  • Like all morbilliviruses, highly contagious
  • Transmission via respiratory route: virions are stable in aerosols for up to an hour depending on humidity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

R0 of MV

A

12-18
> Basic reproductive rate: average number of infected secondary cases produced by each infectious case in a totally susceptible population
> also superspreaders are known with over 200 R0 (very rare)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

MV infection first stage

A

Respiratory tract infection > move to
> Conjunctiva
> upper respiratory tract
> lower respiratory tract including BALT (Bronchus associated lymphoid tissue)
» MV initially infects CD150+ lymphocytes and DC-SIGN+ dendritic cells both in circulation and in lymphoid tissues, followed by virus transmission to nectin-4 expressing epithelial cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Clinical menifestation Latent period and prodrome in MV

A

Latent period and prodrome
> initial innate immune response restricted due to inhibition of the interferon (IFN) response
> there is a latent period of 10-14 days, during this time there is extensive virus replication and spread
> First appearance of disease is a 2-3 day prodrome of fever, runny nose, cough and conjunctivitis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

MV infection second stage

A

Systemic dissemination
> infected myeloid cells (bone marrow) travel to draining lymph nodes
> infect CD150+ cells (B and T cells, depletion of them)
> infected cells migrate to organs and tissues
> skin resident immune cells infect nectin-4 epithelial cells
> MV-specific T-cells infiltrate to skin to clear the infected epithelial cells, resulting in rash

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

MV infection third stage

A

Excretion of new virus particles
> nectin-4+ epithelial cells in upper and lower respiratory tract produce and release new virus particles
> infected lymphoid cells in eg tonsils do the same
> epithelial damage results in coughing > aerosol formation and excretion of large amounts of new virus particles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Clinical manifestation MV: rash and recovery

A
  • Prodrome is followed by appearance of characteristic maculopapular rash that spreads from face and trunk to extremities
    > rash is manifestation of MV-specific adaptive immune response and coincides with clearance of infectious virus
    > however: clearance of viral RNA from blood and tissues is much slower than clearance of infectious virus and proceeds over week to months after the resolution of the rash
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

The period of RNA persistance of MV in the host coincides with…

A

Decreased host resistance to infection that can be prolonged

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Recovery MV is associated with ..

A

Life-long protection from MV re-infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

MV infection associated problems

A
  • Every patient suffers from transient immune suppression
  • Immunodeficiency may be present for up to two years
  • Increased susceptibility to opportunistic infections like secondary pneumonia and gastroenteritis are big problems in the developing world
  • increased risk of mortality
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Measles mortality

A
  • considerable cause of childhood mortality worldwide: more in developing countries
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

MV immune suppression: leukopenia

A

Low total white blood cell count during acute infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

MV induces an anergy-like state in immune cells. What does this mean?

A

Prevention activation and leading to loss of delayed hypersensitivity responses (inflammatory reaction initiated by mononuclear leukocytes)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

MV infection and antibodies repertoire

A

Infection causes elimination of part of the antibody repertoire by depletion of previously expanded B-cell memory clones
> loss of immunity to earlier encountered pathogens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

MV infection and B-cell pools

A

Incomplete reconstitution of naive B-cell pool > compromised bone marrow reconstitution of B-cell diversity > not seen when uninfected are vaccinated.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Name the three MV infection neurologic complications

A

can occur during acute phase or many years later due to long-term persistance of the virus in the CNS.
> ADEM
> MIBE
> SSPE
» MIBE and SSPE: brain is the site of ongoing measles pathology > virus evades immune defenses by spreading from cell to cell within the brain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

ADEM, MIBE and SSPE

A
  • ADEM: acute disseminated encephalomyelitis
    > high mortality and chronic
    > development within 2 weeks of onset rash
    > auto-immune phenomenon as MV is not present in brain
  • MIBE: measles inclusion body encephalitis
    > occurs 1-9 months after acute measles infection in highly immunocompromised individuals (HIV or hematological malignancies)
  • SSPE: subacute sclerosing panencephalitis
    > in immune competent individuals
    > symptoms develop only after a prolonged latent period and the virus from brain tissue is highly defective
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

SSPE

A
  • Only with non-genotype A viruses (other than A)
  • Symptoms after several years after measles: starts with decreased school performace and change bahaviour followed by by myoclonic seizures, ataxia and death within 1-3 years
  • Unclear how virus persists and spreads within CNS: spread without particle formation proposed
    > same order risk as fatal acute measles infection
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

MV vaccination

A
  • recovery associated with lifelong protection
    > MV vaccine strain is live-attenuated genotype A strain
    > can cause mild symptoms as rash, fever and conjunctivitis
    > severe disease is rare and confined to severly immunocompromised patients
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

BMR vaccine in national program

A

14 mo and 9 y age
> Mumps virus: (-) ssRNA, paramyxoviridae (Bof)
> Rubella virus: (+) ssRNA, Togoviridae (Rodehond)
> decreased coverage because antivaxxers
> strategy: vaccination at earlier age

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Top countries outbreak MV

A

Pakistan and Iraq

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

MV eradication

A
  • Because availability highly effective and inexpensive vaccine, monotypic nature of the virus and the lack of animal reservoir
    > candidate for eradication
    > closely related Rinderpest virus has been eradicated as second (after smallpox) virus
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

MV vaccine strain as oncolytic virus

A

> lyse cancer cells
MV vaccine strain has been proven to be safe and oncolytic
overexpression of MV-Edmonston receptor CD46 in many tumor cells may direct virus preferentially to enter transformed cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

MV is highly contagious, respiratory virus, necessitating vaccination with which requirements

A

High coverage (>95%) to provide herd immunity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

What makes measles not so innocent children disease

A

Long lasting sequelae: prolonged immune suppression and early and late possible neurological complications.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

HC07: Norovirus is a two-bucket or double dragon disease, why?

A

It causes vomitting and diarrhea

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Norovirus and rotavirus: same family? and pathogenesis?

A

Both different

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Enteric viruses

A

Picornaviruses, Caliciviruses and Reoviruses families
> naked RNA viruses and icosahedral capsid
> RNA viruses thus higher mutation rate because no proofreading

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Norovirus is the most common virus causing …

A

Acute gastroenteritis (AGE)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Norovirus general character for disease: risk groups, symptoms and diagnosis

A
  • Vomiting, diarrhea, fever, abdominal pain
  • all age groups affected
  • acute infection, self-limiting, symptoms usually last 2-3 days
  • Risk of drying out for young children and eldery
    > more severe infection, dehydration
  • individuals with underlying impaired immunity might get chronic infections of months to years
  • diagnosis by PCR of stool samples
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Big risk of norovirus when someone infected

A

Extremely contagious: few particles can cause disease > low viral load for infection
> also quick reaction for virus to cause disease

41
Q

Where usual quick spreads of norovirus

A

Enclosed places: hospitals, cruise ships, schools and nursing centers.

42
Q

Quick transmission norovirus

A

People are infectous from the start, even when no symptoms yet

43
Q

Transmission NoV

A

Infected individuals shed high loads virus in stool and vomit
> fecal oral route: contact with infected individuals or their excreta
> airborne: infectious aerosols from vomiting: large distances
> food/water borne: exposure to contaminated food and water
> not a lot needed to cause infection

44
Q

Food/water borne NoV

A
  • Leafy greens (lettuce)
  • Fresh fruit
  • Shellfish (oysters and mussels)
    > filter feeders: filter water and hold the virus without infection of themselves
45
Q

NoV in the environment

A

Is stable in the environment: can stay on objects and surfaces for days to weeks and still be infectious
> can survive most disinfectants like alcohol
> hand washing is effective: non-enveloped viruses cannot stand soap
> fast diagnosis essential for outbreak control
> sick personnel in care or food handling should report sick and stay home

46
Q

NoV on cruise ships

A

Because very contagious
> close living quarters may increase group contact
> no effect of raw meat, not a source
> more illness tracking by health officials makes the finding of outbreaks faster: faster isolation

47
Q

Classification NoV

A
  • Caliciviridae (calci= cup)
  • Genus: norovirus
  • (+) ssRNA
  • Non-enveloped
48
Q

Genome NoV

A
  • Not very large
  • 3 ORFs
  • VP1 most important for antigenicity (target antibodies)
  • Virus can make quick mutations in VP1
  • different genera with different relevance for human infection
  • human variant is specific: infects human only
49
Q

Genogroups NoV (GI-X)

A
  • GII. 4 responsible for >85% of outbreaks
  • Each genogroup contains several genotypes
  • Immunity is short-lasting > adaptations
  • New GII.4 variants evolve every 2-3 years to escape herd immunity > cause outbreaks
50
Q

Unknowns NoV in lab

A
  • Hard to culture in vitro: knowledge gap for pathogenesis, hampers vaccine development
  • Hard to make in vivo animal model
  • harder to make vaccines
  • organoids used
51
Q

Replication NoV

A

Inside Bc-cells and intestinal epithelial cells (enterocytes) and possibly macrophages and DCs
> to travel through body
> can infect more cells than only intestinal cells

52
Q

Histo-blood group antigens (HBGAs) in NoV

A

The NoV and rotavirus receptors
> Oligosaccharides linked to proteins or lipids that are expressed on mucosal epithelia of digestive tract
» present in saliva and other secretions
» determinants ABO blood group and Lewis blood groups

53
Q

HBGA fabrication

A

In certain cell types > FUT2 adds fucose group to precursors of HBGAs, generating H HBGAs, and subsequent reactions generate A and B HBGAs (diverse set)

54
Q

Resistance to norovirus (and rotavirus) infection

A
  • Binding specificity of NoV VP1 to different HBGAs differs among NoV genotypes
  • Results in differences in susceptibility of human individuals to specific NoV genotypes
    -Individuals who lack FUT2 are known as non-secretors as A, B and H HBGAs are not present in bodily secretions > less susceptible to infection with several GI and GII strains and to rotavirus P[8] strains
  • around 20% of Northern Europeans are non secretors
55
Q

Noroviruses can bind to intestinal bacteria, how?

A

To membrane or pili
> expression HBGA like structures

56
Q

Role microbiota in NoV infection

A

Both stimualtory and protective is possible

57
Q

Rotavirus character

A

Family Reoviridae
> dsRNA
> Rotavirus A is most important for human infection
> most important diarrhea (gastroenteritis) virus for children below 5 years of age
> lot of hospitilized and mortality among children
> also in other species (group D-I) and human (group A-C)
> symptoms 1-3 days after exposure

58
Q

Risk for children with rotavirus infection

A

Dehydration

59
Q

Structure virion rotavirus

A

Complexer than noro, three laters
> outer: VP4 and VP7 for antigenicity (immune response)
> segmented genome
> dsRNA
> wheel structure
> non-enveloped

60
Q

Genome rotavirus

A
  • 11 segments of dsRNA
  • based on VP7 and VP4 coding gens > into G and P genotypes
    > glycoprotein VP7 and protease sensitive protein VP4\
    > human types
    » G1 to G4, G9 and G12 and P[4], P[6] and P[8]
61
Q

clinical manifestation rota

A
  • NSP4 for pathogenesis: enterotoxin
  • Infect enterocytes
  • Influence water absorption > diarrhea (watery, not bloody, just like noro)
  • antiboides to VP7 and VP4 to neuralize
62
Q

Pathogenesis rota: NSP4 proteins

A
  • Promote calcium ion influx into enterocytes
  • Release of 5-HT from enteroendocrine cells
  • 5-HT induces release neuronal activators and a neuronal alteration in water absorption
  • vomiting center of the brain activated > systemic responses: fever and vomiting
63
Q

Vaccine rota

A

Two commercial on the market
> Rotarix: monovalent live-attenuated human rotavirus G1P[8] genotype
> RotaTeq: live, pentavalent human-bovine reassortment rotavirus containing G1-4 along with P[8]

64
Q

Efficacy rotavirus vaccines

A

They work!
> has to be given early around 8 weeks age > side effect is intussusception (folding intestine)
- reduction hospitalizations for gastro-enteritis
- implementation vaccines substantially decreased hospitalizations, but less impact on worldwide child mortality: eradication not likely

65
Q

Downsides rotavirus vaccines

A
  • Regional and individual differences in efficacy: lower efficiency in low income countries: possible contribution microbiome
  • evidence for reversion of attenuated mutations or reassortment with wild-type rotavirus: dangerous
66
Q

Viral diversity: co-infection of host is key. Why?

A

Reassortment and recombination
> reassortment: segmented virus
» mixtue of fragments from parent A and B to the hybrid progeny
Rocombination for non-segmented
> mixed strand from parents: crossing-over

67
Q

Main obstacles for norovirus vaccine development (none available)

A
  • Immunity is short-lived
  • Difficult to culture, no high virus titers on organoids
  • Lack of animal models
68
Q

HC08: Is there a vaccine against Rabies virus?

A

Yes

69
Q

Most infections Rabies virus through:

A

Dogs
> licks, bites
> vaccination of dogs is being done
> for risk countries where rabies occurs
> also from bat

70
Q

Symptoms rabies

A

Paraesthesia (burning sensations), anxiety, liquid drinking problems

71
Q

Bat rabies in Netherlands

A

European Bat Lyssavirus (EBLV-1) is endemic in bats in Netherlands in serotine bats, low flyers
> Rabies is also a lyssavirus
> Bats which do not follow normal course are mostly sick

72
Q

Bat rabies in Amsterdam

A

Duvenhage virus

73
Q

Mammalian rabies reservoirs and vectors

A

Global diversity: dogs, bats, cats, foxes etc.

74
Q

Strategy rabies

A
  • Improving post-exposure prophylaxis (PEP) for bite victims
  • Provide education on bite prevention
  • Expanding dog vaccination coverage to reduce human exposure risk
75
Q

Wild animals like red foxes in Europe are vaccinated, how?

A

Vaccine bait containing live-attenuated virus
> less prevalence rabies in Europe
> bait of food
> monitored with fluorescent molecule in food > check teeth with night camera

76
Q

Symptoms in rabies dogs

A
  • Unsteady on feet, paralysis
  • Funny sound when bark
  • droopy tongue because swollen salivary glands
  • aggression, biting to spread virus
77
Q

Symptoms human rabies

A
  • Furious 70% or paralytic 30%
  • Starts with flu-like symptoms
  • Then severe headache and nausea
  • Choking, hydrophobia, excessive salivation, painful spasms in laryngeal and pharyngeal muscles when attempting to swallow
  • Oversensitivity to noise and touch
  • paralysis
  • death due to cardiac arrest, circulatory insufficiency or respiratory failure
78
Q

Hydrophobia

A

Fear for water: because when drinking, rabies virus dies in digestive tract, and is transmitted through saliva

79
Q

Family Rhabdoviridae

A

Contains genus lyssaviruses with Rabies virus
- (-) ssRNA
- 14 genotypes of lyssavirus
- Rabies virus (RABV) most prominent
- Hydrophobia specific for RABV
- Animalistic transformation upon RABV infection: mad animal bites man > mad man

80
Q

Typing RABV

A

Enveloped (-) ssRNA
> rod shaped particle

81
Q

Included polymerase in RABV virion

A

To make (+) strand

82
Q

Rotavirus is non-enveloped since its environment is …., but it does have spikes

A

gastro-intestinal
> three capsid layers: stable in GI tract

83
Q

RABV encodes 5 structural proteins

A
  • Nucleoprotein
  • Phosphoprotein
  • Matrix protein
  • Glycoprotein
  • Polymerase
    > N, P, M, G, L
84
Q

Transcription RABV

A

Viral mRNAs are transcribed by polymerase stuttering
> stop and start signals located between ORFs
> in cytoplasm
> make (+) mRNA first from (-) RNA

85
Q

RABV cellular life cycle

A
  • Enter cell via clathrin-mediated endocytosis with help of actin
  • Both receptor recognition and membrane fusion are mediated by single viral glycoprotein (G)
  • Uncoating occurs in endosome due to low pH inducing fusion between G protein and endosomal membrane > release NC in cytoplasm
  • The L gene encodes RdRp: together with phosphoprotein P it forms viral replicase complex (build little virus factories with subcellular localization)
  • New viral particles bud from cell, spike proteins already present
86
Q

RABV spread in host

A
  • Bite infliction
  • Transport along nerve axons
  • Spinal cord
  • Brain
  • Salivary gland
87
Q

RABV uses . receptors on the cell

A

multiple

88
Q

RABV neuroinvasive strategy

A
  • Phospholipids and gangliosides are important for viral entry
  • Multiple proteins can function as viral receptors
    > Enter muscle cells via nAchR (nicotinic acetylcholine receptor) > replicate > spread to neurons or infect neurons directly using NCAM (neuronal cell adhesion molecule), mGluR2 or p75NTR (NGFR, nerve grotwh factor receptor)
89
Q

First replication RABV in …. cells

A

Muscle

90
Q

Axonal transport RABV

A

In endosomes
> use intracellular transport mechanism: microtubule network transport
> involvement dynein and kinesin motors
> active transport

91
Q

Rabies in immunological niche: the CNS, because:

A

It is an immunologically isolated tissue
> tropism for this tissue

92
Q

RABV immuno regulation

A
  • Downregulation interferon response (IFN)
    > inhibition initial IFN induction
    > downstream block on IFN stimulated genes
    > both bt binding RABV-P (phosphoprotein) to various factors with both cytoplasmic and nuclear forms of it made through internal start codons.
  • less immunity in brain
  • better replication
93
Q

RABV-P

A

Determinant RABV pathogenicity
> low levels RABV-P > higher IFN levels and impaired blocking of STAT, transcription inducer of IFN-regulated genes

94
Q

RABV vaccine

A

Protects against phylogroup I lyssaviruses
> live-attenuated vacine: used in wild animals
» risky, can mutate back
» RABV G (glycoprotein) plays important role in pathogenicity, strains with Arg or Lys at 333 position in G protein are virulent and others not
> inactivated vaccine: humans and pets
» FDA has approved 2 of these for human use

95
Q

Human inactivated vaccines for RABV

A
  • Imovax: after 2 injections, 100% recipients developed protective antibodies
  • RabAvert: after 3 injections, 100% of trial subjects attained a protective titer
96
Q

Death rabies always when

A

Symptomatic

97
Q

Post-exposure prophylaxis (PEP) treatment of RABV infection

A
  • Wash wound with soap and water
  • Give rabies specific IgG when not vaccinated before
    > serum, no monoclonal antibodies approved yet
    > from vaccinated patients
  • Vaccinate, transport of virus from wound to brain can take a long time > it helps to do post-infection before disease!
98
Q

Children more at risk in RABV, higher mortality, why>

A

Smaller
> when dog bites leg, shorter route to the brain (less distance to travel) > less time to get vaccination
> more bites in face
> more vulnerable

Medical Microbiology (11 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions